Sue Harrison

Cognitive outcome after extratemporal epilepsy surgery in childhood

Purpose:  The present study aims to describe the cognitive profile of children with medically refractory extratemporal epilepsies who undergo focal surgery and to identify determinants for preoperative and postoperative cognitive level.

Pyridoxine-dependent seizures: a family phenotype that leads to severe cognitive deficits, regardless of treatment regime.

The neuropsychological and clinical histories of three male siblings affected by pyridoxine‐dependent seizures with known homozygous antiquitin mutations are presented. Neuropsychological evaluation is reported from when the siblings were 11, 9, and 7 years of age. Two of the siblings had received early pyridoxine treatment (antenatal, 2–4wks into pregnancy) and one had received late treatment (2mo postnatal). However, there was no differential effect on cognitive outcome, with all three siblings having moderate to severe learning disability. Unlike previously reported cases that received early postnatal treatment, none of the siblings had relatively preserved non‐verbal cognitive skills. Equally, their intellectual performance over time did not increase above the 1st centile despite high maintenance doses of vitamin B6 (range 16–26mg/kg/d), and mild sensory neuropathy was reported on nerve conduction studies. The findings in these siblings challenge assumptions that early and high dose pyridoxine treatment can benefit cognition in this population and suggest routine electromyography monitoring may be beneficial.

Temporal lobe surgery in childhood and neuroanatomical predictors of long-term declarative memory outcome

See Berg (doi:10.1093/brain/awu320) for a scientific commentary on this article. In a long-term follow-up study of children who underwent temporal lobe surgery for treatment of epilepsy, Skirrow et al. identify no significant pre-to-post-surgery memory losses, but instead robust improvements in memory functions supported by the unoperated temporal lobe. The integrity of remaining temporal lobe structures places constraints on long-term memory outcomes.

Intelligence quotient improves after antiepileptic drug withdrawal following pediatric epilepsy surgery.

Antiepileptic drugs (AEDs) have cognitive side effects that, particularly in children, may affect intellectual functioning. With the TimeToStop (TTS) study, we showed that timing of AED withdrawal does not majorly influence long‐term seizure outcomes. We now aimed to evaluate the effect of AED withdrawal on postoperative intelligence quotient (IQ), and change in IQ (delta IQ) following pediatric epilepsy surgery.

Seizure outcome after extratemporal epilepsy surgery in childhood

Aim  The aim of the study was to describe seizure outcome following surgery for focal extratemporal epilepsy and identify factors associated with prolonged postsurgical freedom from seizures.

Impact of interictal epileptic activity on normal brain function in epileptic encephalopathy: An electroencephalography–functional magnetic resonance imaging study

Using electroencephalography (EEG) in combination with functional magnetic resonance imaging (fMRI), we studied a 9.5-year-old girl who developed cognitive and behavioral regression in association with intense interictal bilaterally synchronous epileptic discharges (IBSEDs) both during the awake state and during sleep. During runs of IBSEDs, EEG-fMRI demonstrated deactivations in the lateral and medial frontoparietal cortices, posterior cingulate gyrus, and cerebellum together with focal relative activations in the right frontal, parietal, and temporal cortices. The deactivations probably reflect the repercussion of the interictal epileptic activity on normal brain function which might cause the neuropsychological regression by inducing repetitive interruptions of neurophysiological function resulting in a chronic state of specific psychomotor impairment. The relative activations could possibly indicate the source of epileptic activity rapidly spreading to other brain regions.

Interictal epileptiform discharges have an independent association with cognitive impairment in children with lesional epilepsy

The relative contribution of interictal epileptiform discharges (IEDs) to cognitive dysfunction in comparison with the underlying brain pathology is not yet understood in children with lesional focal epilepsy.

Asymmetry of planum temporale constrains interhemispheric language plasticity in children with focal epilepsy

Reorganization of eloquent cortex enables rescue of language functions in patients who sustain brain injury. Individuals with left-sided, early-onset focal epilepsy often show atypical (i.e. bilateral or right-sided) language dominance. Surprisingly, many patients fail to show such interhemispheric shift of language despite having major epileptogenic lesions in close proximity to eloquent cortex. Although a number of epilepsy-related factors may promote interhemispheric plasticity, it has remained unexplored if neuroanatomical asymmetries linked to human language dominance modify the likelihood of atypical lateralization. Here we examined the asymmetry of the planum temporale, one of the most striking asymmetries in the human brain, in relation to language lateralization in children with left-sided focal epilepsy. Language functional magnetic resonance imaging was performed in 51 children with focal epilepsy and left-sided lesions and 36 healthy control subjects. We examined the association of language laterality with a range of potential clinical predictors and the asymmetry of the length of the planum temporale. Using voxel-based methods, we sought to determine the effect of lesion location (in the affected left hemisphere) and grey matter density (in the unaffected right hemisphere) on language laterality. Atypical language lateralization was observed in 19 patients (38%) and in four controls (11%). Language laterality was increasingly right-sided in patients who showed atypical handedness, a left perisylvian ictal electroencephalographic focus, and a lesion in left anterior superior temporal or inferior frontal regions. Most striking was the relationship between rightward asymmetry of the planum temporale and atypical language (R = 0.70, P < 0.0001); patients with a longer planum temporale in the right (unaffected) hemisphere were more likely to have atypical language dominance. Voxel-based regression analysis confirmed that increased grey matter density in the right temporo-parietal junction was correlated with right hemisphere lateralization of language. The length of the planum temporale in the right hemisphere was the main predictor of language lateralization in the epilepsy group, accounting for 48% of variance, with handedness accounting for only a further 5%. There was no correlation between language lateralization and planum temporale asymmetry in the control group. We conclude that asymmetry of the planum temporale may be unrelated to language lateralization in healthy individuals, but the size of the right, contra-lesional planum temporale region may reflect a ‘reserve capacity’ for interhemispheric language reorganization in the presence of a seizure focus and lesions within left perisylvian regions.

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty‐six epilepsy centers and members of “E‐PILEPSY” (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co‐normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.

Seizure and cognitive outcomes after resection of glioneuronal tumors in children

Glioneuronal tumors (GNTs) are well‐recognized causes of chronic drug‐resistant focal epilepsy in children. Our practice involves an initial period of radiological surveillance and antiepileptic medications, with surgery being reserved for those with radiological progression or refractory seizures. We planned to analyze the group of patients with low‐grade GNTs, aiming to identify factors affecting seizure and cognitive outcomes.