Newborn with Refractory Seizures due to Hemimegalencephaly and Tuberous Sclerosis Complex: Case Report and Literature Review

Abstract

Hemimegalencephaly (HME) is a rare congenital disorder that is initiated during embryonic development with abnormal growth of one hemisphere. Tuberous sclerosis complex (TSC), a genetic disorder, is rarely associated with HME.We present a case of a newborn with HME with a confirmed mutation in the TSC-1 gene and describe the clinical course, findings on amplitude-integrated electroencephalography (aEEG), cranial ultrasound (CUS), MRI, and the postmortem evaluation. Furthermore, we conducted a comprehensive literature review of all reported newborns with HME and a genetically confirmed TSC mutation.This infant experienced therapy-resistant seizures after birth despite treatment with multiple antiseizure medications. CUS and MRI revealed HME of the left hemisphere. Early functional hemispherectomy, around the age of 3 months, was considered but dismissed after multidisciplinary evaluation, medical ethical consultation, and multiple discussions with the parents. Care was redirected due to worsening clinical and neurologic conditions, increasing respiratory insufficiency, and ongoing therapy-resistant seizures. Postmortem evaluation of the brain revealed hamartomatous brain changes and irregular gyration of the enlarged hemisphere. in addition, these changes were also present in the previously considered unaffected side, raising thoughts about the potential effectiveness of functional hemispherectomy.This case report illustrates that in cases with TSC abnormalities might not be confined solely to the initially considered affected side. This can have important therapeutic implications.

Fig. 1

aEEG and EEG tracings of the infant with HME. The aEEG ( A, B ) of this infant showed a continuous, high-voltage pattern on the left hemisphere with a cut-off of the seizures. There was asymmetry in bandwidth between both hemispheres, the left is slightly narrower (F3-P3). Ictal discharges (arrow) were seen in both hemispheres. No seizure reduction was observed on aEEG after the administration of levetiracetam (lev) and midazolam (mida). Temporary effects of 4 hours and 20 minutes without epileptic activity were observed after the loading dose of lidocaine (lido). EEG ( C, D ) showed an interictal asymmetric background activity, with higher amplitudes and slower activity on the left hemisphere as compared with the right ( C ). The ictal activity consisted of high-voltage rhythmic discharges, most pronounced in the left occipital region, showing evolution in frequency and amplitude ( D ). aEEG, amplitude-integrated electroencephalography; EEG, electroencephalography; HME, hemimegaloencephaly.

Fig. 2

CUS and MRI images of the brain illustrating HME. Cranial ultrasound ( A, B ) showed an enlarged left hemisphere and cortical blurring of the left parieto-occipital structures. Increased echo density in the white matter on both the coronal and sagittal views was seen. T2-weighted MRI images showing a deviant hypointense thickened left temporal ( C ), and parieto-occipital cortex ( D ) (pachygyria) with decreased gyration in the left hemisphere. Subependymal noduli were present on the left side. CUS, cranial ultrasound; HME, hemimegaloencephaly.