Background In acute respiratory distress syndrome (ARDS) unrelated to COVID-19, two phenotypes, based on the severity of systemic inflammation (hyperinflammatory and hypoinflammatory), have been described. The hyperinflammatory phenotype is known to be associated with increased multiorgan failure and mortality. In this study, we aimed to identify these phenotypes in COVID-19-related ARDS. Methods In this prospective observational study done at two UK intensive care units, we recruited patients with ARDS due to COVID-19. Demographic, clinical, and laboratory data were collected at baseline. Plasma samples were analysed for interleukin-6 (IL-6) and soluble tumour necrosis factor receptor superfamily member 1A (TNFR1) using a novel point-of-care assay. A parsimonious regression classifier model was used to calculate the probability for the hyperinflammatory phenotype in COVID-19 using IL-6, soluble TNFR1, and bicarbonate levels. Data from this cohort was compared with patients with ARDS due to causes other than COVID-19 recruited to a previous UK multicentre, randomised controlled trial of simvastatin (HARP-2). Findings Between March 17 and April 25, 2020, 39 patients were recruited to the study. Median ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air (PaO 2 /FiO 2 ) was 18 kpa (IQR 15–21) and acute physiology and chronic health evaluation II score was 12 (10–16). 17 (44%) of 39 patients had died by day 28 of the study. Compared with survivors, patients who died were older and had lower PaO 2 /FiO 2 . The median probability for the hyperinflammatory phenotype was 0·03 (IQR 0·01–0·2). Depending on the probability cutoff used to assign class, the prevalence of the hyperinflammatory phenotype was between four (10%) and eight (21%) of 39, which is lower than the proportion of patients with the hyperinflammatory phenotype in HARP-2 (186 [35%] of 539). Using the Youden index cutoff (0·274) to classify phenotype, five (63%) of eight patients with the hyperinflammatory phenotype and 12 (39%) of 31 with the hypoinflammatory phenotype died. Compared with matched patients recruited to HARP-2, levels of IL-6 were similar in our cohort, whereas soluble TNFR1 was significantly lower in patients with COVID-19-associated ARDS. Interpretation In this exploratory analysis of 39 patients, ARDS due to COVID-19 was not associated with higher systemic inflammation and was associated with a lower prevalence of the hyperinflammatory phenotype than that observed in historical ARDS data. This finding suggests that the excess mortality observed in COVID-19-related ARDS is unlikely to be due to the upregulation of inflammatory pathways described by the parsimonious model. Funding US National Institutes of Health, Innovate UK, and Randox.

Gelastic seizures in hypothalamic hamartoma arise from the hamartoma itself; the interictal spike-wave does not. The evolution of EEG abnormalities, the development of generalized seizures years after onset of gelastic seizures, and the postoperative running down of interictal spike-wave and generalized seizures in these patients may reflect secondary epileptogenesis.

SUMMARYPurpose: Febrile infection-related epilepsy syndrome (FIRES) is an increasingly recognized epileptic syndrome that presents with multifocal refractory status epilepticus in previously normal children and evolves into a chronic, refractory, focal epilepsy with associated cognitive and behavioral difficulties. Herein we describe the features of the chronic epilepsy and critically review evidence for the etiology of this syndrome. Methods: Seven patients with FIRES were studied. The duration of follow-up in six survivors was 5-17 years. Clinical, electroencephalography (EEG), neuroimaging, and other investigative findings during the acute and chronic phases were reviewed. Key Findings: These previously normal children presented with a febrile illness and status epilepticus that was refractory to antiepileptic medications in all children, to immunotherapies (including immunoglobulin, corticosteroids, plasma exchange, and rituximab) in four, and to acute vagus nerve stimulation in one. Markers of cerebral inflammation were few and response to antiepileptic and immunomodulatory therapies was poor. Evolution to chronic epilepsy occurred without a silent period. Seizure characteristics in the chronic phase were strikingly stereotyped and similar to the acute phase, with head and eye version, unilateral facial jerking, asymmetric tonic posturing, and unilateral limb jerking in all patients. Electrographic ictal onset was lateralized in all recorded seizures, unilateral in one patient, and independent bilateral in three. Seizures were refractory to multiple antiepileptic medications in all patients and partly responsive to chronic vagus nerve stimulation in two patients. Moderate to severe intellectual impairment was noted in four patients, and borderline intellectual abilities were noted in two. Magnetic resonance imaging (MRI) in the chronic phase was normal in three patients and showed mild diffuse cortical atrophy and/or mild hippocampal atrophy or sclerosis in three. Significance: The similar perirolandic and perisylvian features of acute and chronic seizures, the lack of a silent period, the absence of evidence of cerebral inflammation, and the poor response to immunotherapies suggest FIRES is best conceptualized as a chronic epilepsy with explosive onset, not a remote-symptomatic epilepsy with an acute inflammatory antecedent.

SUMMARYPurpose: Vagus nerve stimulation (VNS) is used increasingly as adjunctive therapy for refractory epilepsy. Studies of VNS in children report mainly seizure frequency reduction as a measure of efficacy and clinical details are often scanty. We report our experience with VNS in children with refractory epilepsy and emphasize the positive effects of VNS in terms of seizure severity. Methods: We reviewed 26 consecutive children who had VNS with a minimum follow-up period of 18 months. We examined their clinical characteristics, seizure types, seizure frequency, epilepsy syndrome diagnosis, and response to VNS in terms of seizure frequency and seizure severity.Results: Fifty-four percent of patients responded to VNS with ‡50% seizure frequency reduction. Patients with Lennox-Gastaut syndrome (LGS) and tonic seizures had a higher responder rate; 78% (seven of nine patients) (p < 0.01). Status epilepticus (SE) episodes were reduced or ceased in the four patients with recurrent SE. Seizure severity, duration, and recovery time decreased in all responders. Increased alertness was reported in all responders and three nonresponders. Conclusion: Decreased seizure severity, recovery time, abolition of daytime drop attacks, and reduced hospitalization due to SE improved patients' lives over and above the benefit from seizure frequency reduction. KEY WORDS: Vagus nerve stimulation, Tonic seizures, Lennox-Gastaut syndrome.Vagus nerve stimulation (VNS) is a form of neurostimulation therapy, primarily indicated for refractory epilepsy. It consists of a generator implanted in the anterior chest wall that delivers intermittent electric stimuli to the brain via a bipolar electrode coiled around the left vagus nerve in the neck. The generator cycles continuously at predetermined parameters. VNS is being used increasingly as adjunctive therapy for patients with epilepsy that is resistant to antiepileptic medications and not suitable for resective surgery. First performed in humans in 1988 for treatment of refractory epilepsy (Penry & Dean, 1990), VNS is used to treat an estimated >50,000 patients worldwide (De Herdt et al., 2007). The majority of patients treated with VNS have focal epilepsy, but in children, VNS is used more often in patients with symptomatic generalized epilepsy (Parker et al., 1999;Frost et al., 2001;Majoie et al., 2001Majoie et al., , 2005Nagarajan et al., 2002). Most studies report a 50% or greater reduction of seizure frequency in 40-50% of patients (Ben-Menachem et al., 1994;Amar et al., 1998;Handforth et al., 1998;Morris & Mueller, 1999;Vonck et al., 2004;De Herdt et al., 2007) without any greater benefits in certain syndromes or seizure types.The exact mechanism by which VNS modulates seizures is not known. The vagus nerve, comprising 80% afferent fibers originating from the heart, lungs, larynx, pharynx, and gastrointestinal tract, transmits visceral sensory information to the central nervous system. The vagus nerve projects primarily to the nucleus of the solitary tract, which has projections to mult...

Summary Purpose:  Studies in adult and neonatal intensive care units (ICUs) report a high prevalence of epileptic seizures in comatose patients. The prevalence of seizures in pediatric ICUs is variably reported in a few retrospective studies using different electroencephalography (EEG) methods. We aimed to determine prospectively the prevalence of epileptic seizures (clinical and subclinical) in comatose children in the pediatric ICU using continuous video‐EEG (v‐EEG) monitoring. Methods:  We performed v‐EEG in consecutive children aged 2 months to 17 years admitted to the pediatric ICU with sustained depressed consciousness over a period of 15 months. Results:  We monitored 100 comatose children, 69% within 24 h of ICU admission. Median length of ICU stay was 5 days. Median duration of v‐EEG was 20 h. Epileptic seizures were identified in only seven patients, of whom six had a history of epilepsy with witnessed seizures immediately prior to v‐EEG. All epileptic seizures were recorded in the first 3 h of v‐EEG. Seizures were suspected by ICU staff in 18 monitored patients, only four of whom had confirmed epileptic seizures. Discussion:  The lower prevalence of epileptic seizures and the shorter length of ICU stay in children compared to adults and neonates suggest a different spectrum of disease and neurologic response. Short‐duration v‐EEG in patients with a history of prior seizures, epilepsy, or clinical events suspected to be seizures seems more appropriate than routine v‐EEG in all comatose children in the pediatric ICU.