Acute encephalopathy in children with tuberous sclerosis complex

Abstract

Objective: We examined the clinical manifestations of acute encephalopathy (AE) and identify risk factors for AE in children with tuberous sclerosis complex (TSC).

Methods: The clinical data of 11 children with clinically diagnosed TSC associated with AE and 109 children with clinically diagnosed TSC alone aged 4 years or older were collected from 13 hospitals.

Results: Of the 11 children with AE, 5 had histories of febrile seizures (FS), and all had histories of febrile status epilepticus (FSE). AE developed within 24 h after fever onset in all children with seizures lasting 30 min or longer. All children developed coma after seizure cessation. Head magnetic resonance imaging (MRI) revealed widespread abnormalities in the cerebral cortex, subcortical white matter, corpus callosum, basal ganglia, and thalamus. One child died; seven had severe neurological sequelae; and the other three, mild sequelae. Logistic regression analysis revealed that a history of FSE was correlated with the development of AE.

Significance: AE in children with TSC was characterized by sudden onset after fever, followed by coma, widespread brain edema evident on MRI, and poor outcomes. A history of FSE was a risk factor for the development of AE.

Keywords: Clinical neurology history; Infantile spasms; MRI; Prognosis; Status epilepticus.

Fig. 1

MRI findings. a, b MRI findings in patient 1 at the onset of acute encephalopathy (AE). Reduced water diffusion was evident over the entire cerebral cortex and the posterior parts of the thalami (a diffusion-weighted images; b apparent diffusion coefficient map). c–e MRI of patient 1 performed 4 days after AE onset. Marked brain edema with narrowing of the lateral ventricles was seen on T1- (c) and T2-weighted (d) images. Diffusion-weighted images exhibited reduced water diffusion, predominantly in the subcortical white matter (e). f MRI of patient 3 performed 7 days after AE onset. Diffusion-weighted images revealed reduced water diffusion in the subcortical white matter and corpus callosum. g MRI of patient 4 performed 3 days after AE onset. Reduced water diffusion was evident in the subcortical white matter of the left frontal and bilateral temporo–parieto–occipital areas. h MRI of patient 6 performed 5 days after AE onset. Reduced water diffusion was evident in the bilateral thalami and subcortical white matter, except for the bilateral occipital areas. i MRI of patient 2 performed 17 days after AE onset. Diffusion-weighted images revealed reduced water diffusion in the caudate nuclei, basal ganglia, and the pulvinar thalami