Fetal Brain Magnetic Resonance Imaging Findings Predict Neurodevelopment in Children with Tuberous Sclerosis Complex

Abstract

on behalf of the EPISTOP consortium †Objective To correlate fetal brain magnetic resonance imaging (MRI) findings with epilepsy characteristics and neurodevelopment at 2 years of age in children with tuberous sclerosis complex (TSC) to improve prenatal counseling.Study design This retrospective cohort study was performed in a collaboration between centers of the EPISTOP consortium. We included children with definite TSC, fetal MRIs, and available follow-up data at 2 years of age. A pediatric neuroradiologist masked to the patient's clinical characteristics evaluated all fetal MRIs. MRIs were categorized for each of the 10 brain lobes as score 0: no (sub)cortical lesions or doubt; score 1: a single small lesion; score 2: more than one small lesion or at least one large lesion (>5 mm). Neurologic manifestations were correlated to lesion sum scores.Results Forty-one children were included. Median gestational age at MRI was 33.3 weeks; (sub)cortical lesions were detected in 97.6%. Mean lesion sum score was 4.5. At 2 years, 58.5% of patients had epilepsy and 22% had drug-resistant epilepsy. Cognitive, language, and motor development were delayed in 38%, 81%, and 50% of patients, respectively. Autism spectrum disorder (ASD) was diagnosed in 20.5%. Fetal MRI lesion sum scores were significantly associated with cognitive and motor development, and with ASD diagnosis, but not with epilepsy characteristics.Conclusions Fetal cerebral lesion scores correlate with neurodevelopment and ASD at 2 years in children with TSC.

Effects of Mutations in TSC Genes on Neurodevelopment and Synaptic Transmission

“…Age of seizures onset can have an effect on ASD symptoms, but seizures do not seem to be necessary for their appearance. In fact, 21% of the children at risk of ASD and 11% of the ones with developmental delay at 24 months have no previous epilepsy history [ 30 ], and fetal lesions revealed by MRI imaging correlate with cognitive developmental deficits, but not with epilepsy [ 31 ]. Nevertheless, alterations in EEG appear to precede the onset of epileptic events, thus further pointing to the high importance of the early postnatal neuronal network functioning for subsequent development [ 32 ].…”

Risk Factors Associated with Refractory Epilepsy in Patients with Tuberous Sclerosis Complex: A Systematic Review

“…During full text analysis, additional thirty-one reports were excluded as they either did not meet inclusion or met exclusion criteria ( Figure 1 ). Overall, 19 reports were included in the systematic review [ 2 , 10 , 12 , 14 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The inclusion and exclusion criteria available for each article are included in Table 1 .…”

“…Ten studies (52.6%) used the exact ILAE 2010 definition of drug-resistant epilepsy: “a failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom” [ 3 ]. Of those, Hulshof et al specified the threshold age for control as two years [ 14 ]. Other studies applied other various definitions of DRE.…”

“…Four of those defined FCD as cortical tubers and ascertained the threshold number of tubers: seven and more cortical tubers [ 21 ], four and more [ 26 ], “at least one cyst-like cortical tuber” [ 2 ]. The last one compared the number of tubers 4.89 vs. 4.41 in DRE and non-refractory epilepsy, respectively, though the difference was not statistically significant [ 14 ].…”

“…Current diagnostic methods such as prenatal echocardiography, brain magnetic resonance imaging (MRI), and EEG monitoring allow an early diagnosis before the onset of clinical seizures enabling early disease-modifying treatment [ 14 ]. As a consequence, preventive treatment is becoming more approved and often introduced in clinical centers [ 15 ].…”