Early non-convulsive seizures are associated with the development of acute encephalopathy with biphasic seizures and late reduced diffusion

Abstract

Introduction

Children with either febrile seizure or acute encephalopathy exhibit seizures and/or impaired consciousness accompanied by fever of unknown etiology (SICF). Among children with SICF, we previously reported those who have refractory status epilepticus or prolonged neurological abnormalities with normal AST levels are at a high risk for the development of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), considered to be caused by excitotoxicity. Non-convulsive seizures (NCS) are common in critically ill children and cause excitotoxic neuronal injury. The aim of this study was to elucidate the prevalence of NCS in the acute phase of children at a high risk for developing AESD and the relationship between NCS in the acute phase and neurological outcomes.

Methods

We studied 137 children with SICF at a high risk for developing AESD and who underwent continuous electroencephalogram monitoring (cEEG) upon admission to a tertiary pediatric care center at Hyogo Prefectural Kobe Children’s Hospital between October 2007 and August 2018. Patient characteristics and outcomes were compared between patients with NCS and without NCS.

Results

Of the 137 children, NCS occurred in 30 children; the first NCS were detected in cEEG at the beginning in 63.3%, during the first hour in 90%, and within 12 h in 96.7%. Neurological sequelae were more common in NCS patients (20.0%) than in non-NCS patients (1.9%; p = 0.001). Five in 30 NCS patients (16.7%) and 3 in 107 non-NCS patients (2.8%) developed AESD (p = 0.013).

Conclusion

The occurrence of NCS is associated with subsequent neurological sequelae, especially the development of AESD.

Introduction

Children with febrile seizure (FS) and acute encephalopathy (AE) exhibit seizures and/or impaired consciousness accompanied by fever of unknown etiology (SICF) [1]. FS is a transient condition in which children do not experience sequelae, and usually do not require intensive care. AE is defined as impaired consciousness lasting longer than 24 h and is often associated with neurological sequelae and thus requires intensive care [2]. Because FS and AE are indistinguishable at the onset of SICF, we developed and validated a clinical prediction rule for neurological sequelae due to AE, which consists of the following 3 variables as predictive of poor outcomes: 1) refractory convulsive status epilepticus (RSE); 2) prolonged neurological abnormalities at 6 h from onset, and 3) aspartate aminotransferase (AST) > 90 IU/L within 6 h of onset [3], [4]. Furthermore, we also found that children with SICF who have RSE or prolonged neurological abnormalities with normal AST levels (1) and/or 2) without 3)) are at a high risk for developing acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) [3], [4]. While AESD is usually preceded by febrile status epilepticus (early seizure), followed by clustered seizures (late seizure) at day 4 to 6 and thought to be caused by excitotoxicity, some patients (~20%) do not have prolonged early seizure [5]. Excitotoxicity is caused by prolonged seizures, regardless of whether these are convulsive or non-convulsive seizures (NCS) [6]. Recent studies have reported that NCS were found in 7%-46% of critically ill children in the intensive care unit (ICU) [7], [8] and 16.9% of children with altered mental status in the emergency room [9]. We hypothesized that neurological sequelae and development of AESD are associated with NCS around the early seizure. In this study, we aimed to retrospectively investigate the prevalence of NCS among children at a high risk for developing AESD and the association between NCS in the acute phase and neurological sequelae.