A 9-year-old boy was outborn at term without complications as the first child of non-consanguineous and healthy parents after a complicated course of pregnancy (vaginal bleeding on gestational week 12, gestational diabetes). Postpartum weakness of the left arm was noted. He was first presented to our Center for Chronically Sick Children at 2.6 years of age. He had spastic hemiparesis affecting particularly the left arm, hemineglect, and intermittent spontaneous nystagmus. A cranial MRI revealed a cystic parenchyma defect of the right parietotemporal side due to an ischemic stroke of his middle cerebral artery (Figure 1A). At this point, he had no reported seizures.
At the age of 9 years, the patient presented again because of global developmental delay, hemiparesis, and drug-refractory epilepsy with persistent seizures. ASM treatment with VPA (18.75 mg/kg/day) and lamotrigine (LTG) (0.95 mg/kg/day) failed to control the seizures. First focal-onset seizures had occurred at 4 years of age. Over time, these gradually shifted to focal-onset seizures with increasingly impaired awareness. At presentation, he had focal to tonic-clonic seizures every 8 weeks. He showed appropriate engagement during social contact with a slight decrease in proximity-distance regulation. In neuropsychological examination, difficulties in attentional control, impulse control, and inhibition, as well as slightly increased motor agitation could be observed. Furthermore, he showed reduced stress resilience and frustration tolerance in the presence of excessive emotions. Because of highly increased emotional stress of the parents, it was not possible to examine neuropsychological data via questionnaires.
We classified the patient as drug-resistant and included him in our epilepsy surgery program. Further investigations with congruent findings in MRI and EEG led to the indication for hemispherotomy. A vertical parasagittal hemispherotomy on the right side was performed without complications. Since then, the patient has remained seizure-free (Figure 1B).
Two weeks after surgery, he showed an acute increase in psychological problems. He showed an acute aggravation of neuropsychological issues: hyperactivity, inhibition, and attentional control. The patient was restless and hardly controllable during medical examinations. Furthermore, the parents and teachers reported an increased tendency to aggressive behavior, which led to an exclusion from school. Overall, the symptoms had a high impact on the well-being of the family and the patient. An EEG showed no evidence of leftward transition with no evidence of clinical seizure signs (Figure 2A).
We considered these behavioral problems to be related to the postoperatively changed neuronal networks of the brain. This working hypothesis was based on clinical experience by one of the senior authors (CE) on VPA-induced behavioral disturbances after epilepsy surgery that has not been reported previously. Already after VPA reduction from 18.75 to 14 mg/kg/day, the behavioral problems decreased. Once VPA was tapered-off, the behavioral problems were back at the preoperative level. Serum levels of the ASM of the patient were not measured. An EEG performed 6 months post-operatively showed no evidence of seizures (Figure 2B). A standardized neuropsychological follow-up assessment 6, 12, and 24 months postoperatively revealed a significant improvement in attention span, inhibitory skills, and frustration tolerance. Aggressive behavior was not detected during the medical examinations. The parents reported them to be absent during everyday life.