Multilobar unilateral hypoplasia with emphasis on the posterior quadrant and severe epilepsy in children with FCD ILAE Type 1A.

OBJECTIVE: Focal cortical dysplasia (FCD) Type 1 and its three subtypes have yet not been fully characterized at the clinical, anatomopathological, and molecular level (International League Against Epilepsy [ILAE] FCD classification from 2011). We aimed to describe the clinical phenotype of patients with histopathologically confirmed FCD1A obtained from a single epilepsy center between 2002 and 2016. METHODS: Medical records were retrieved from the hospital's archive. Results from electroencephalography (EEG) video recordings, neuroimaging, and histopathology were reevaluated. Magnetic resonance imaging (MRI) post-processing was retrospectively performed in nine patients. DNA methylation studies were carried out from archival surgical brain tissue in 11 patients. RESULTS: Nineteen children with a histopathological diagnosis of FCD1A were included. The average onset of epilepsy was 0.9 years (range 0.2-10 years). All children had severe cognitive impairment and one third had mild motor deficits, yet fine finger movements were preserved in all patients. All patients had daily seizures, being drug resistant from disease onset. Interictal electroencephalography revealed bilateral multi-regional epileptiform discharges. Interictal status epilepticus was observed in 8 and countless subclinical seizures in 11 patients. Regional continuous irregular slow waves were of higher lateralizing and localizing yield than spikes. Posterior background rhythms were normal in 16 of 19 children. Neuroimaging showed unilateral multilobar hypoplasia and increased T2-FLAIR signals of the white matter in 18 of 19 patients. All children underwent tailored multilobar resections, with seizure freedom achieved in 47% (Engel class I). There was no case with frontal involvement without involvement of the posterior quadrant by MRI and histopathology. DNA methylation profiling distinguished FCD1A samples from all other epilepsy specimens and controls. SIGNIFICANCE: We identified a cohort of young children with drug resistance from seizure onset, bad EEG with posterior emphasis, lack of any focal neurological deficits but severe cognitive impairment, subtle hypoplasia of the epileptogenic area on MRI, and histopathologically defined and molecularly confirmed by DNA methylation analysis as FCD ILAE Type 1A.

Sacrificing one visual hemifield during pediatric epilepsy surgery: Effects on visual search.

OBJECTIVES: To investigate early and late effects of planned surgically acquired homonymous hemianopias on visual search in children and adolescents. METHODS: This prospective study included five patients (5y 5 m-18y 0 m; 2 girls) with pharmaco-refractory epilepsies in whom one visual hemifield was sacrificed as part of the surgical strategy, and, as controls, seven patients (5y 11 m-18y 0 m; 6 girls) undergoing epilepsy surgeries not affecting the visual fields. Visual search was studied using the "Table Test", which is an everyday life-like visual search test. General processing speed was studied using a standard IQ subtest. RESULTS: All five patients with newly acquired homonymous hemianopias showed a relative disadvantage of visual search times for objects in their newly blind hemifields immediately after the surgery. Six months later, this relative disadvantage had recovered completely in all patients. Nevertheless, compared with the preoperative situation, overall search times were still prolonged in the hemianopic patients, but this effect could be mitigated or even overcompensated by improvements in processing speed. CONCLUSIONS: Children with homonymous hemianopias inflicted by epilepsy surgery develop effective compensation strategies to minimize the relative disadvantage of visual search in their blind hemifields. For changes in overall visual search times between the preoperative and the six-month follow-up examination, we could demonstrate overlapping effects of (a) deterioration by hemianopia and (b) amelioration by improved processing speed as part of the cognitive improvements achieved by amelioration of the epilepsy.

Correlates of intellectual development before and after hemispherotomy: an analysis of 75 children and adolescents.

This study describes the intellectual development of 75 children and adolescents who underwent hemispherotomy. Furthermore, we aimed to reveal predicting factors on pre- and postsurgical development with a focus on the role of aetiology. We analysed presurgical and six-month postsurgical developmental and intellectual data of 75 patients (age range: 0.87-19.78 years) and divided them into two groups: a not severely impaired group in which outcome of intellectual functioning was reported based on FSIQ score, and a severely impaired group (not testable by IQ tests) in which intellectual developmental outcome was described based on developmental quotients instead. In the not severely impaired group (n = 31), the preoperative level of intellectual functioning was a strong predictor of postoperative intellectual outcome; for 22/31 (71%) patients, postoperative FSIQ and its subscales were similar to preoperative levels. Improvements were observed for FSIQ in five patients, only for Verbal IQ in one patient and only for Performance IQ in one further patient; significant losses occurred in two patients, only for Performance IQ in both. In the severely impaired group, 30/40 (75%) patients showed further development after surgery, nine (23%) patients had the same results as before surgery, and one (2%) patient showed regression. Longer duration of presurgical epilepsy was related to a marginally lower presurgical developmental level, and good seizure outcome was a predictor of better postoperative development. For all patients, early age at seizure onset and early lesion origin correlated with poorer presurgical intellectual development. Although an entire hemisphere was disconnected, most patients exhibited ongoing development after hemispherotomy or had at least the same preoperative intellectual status; deterioration was rare.

Presurgical Language fMRI in Children, Adolescents and Young Adults : A Validation Study.

PURPOSE: To validate four established, child-friendly functional magnetic resonance imaging (fMRI) language tasks (word chain task [WCT], vowel identification task [VIT], synonym task [SYT] and beep story task [BST]) in a predominantly pediatric cohort. METHODS: Intracarotid amobarbital procedures (IAP) (n = 17) and unchanged language after hemispherotomy (n = 6) were used as gold standards. The fMRI activations of nine regions of interest (ROI) in the frontal, temporal and parietal lobes as well as in the cerebellum were visually assessed in 23 fMRI examinations (in total 117 fMRI task sessions) of 23 patients (age range 10.0-23.0 years) with drug-refractory epilepsies. RESULTS: The ROIs were considered valid when they showed activation in more than 25% of all sessions for the respective task and never showed false lateralization (in comparison to gold standards). Thus, 13 valid, task-specific ROIs were identified: 5 ROIs for the WCT (frontal operculum, inferior frontal gyrus, middle frontal gyrus, intraparietal sulcus, cerebellum), 3 ROIs for the VIT (frontal operculum, inferior frontal gyrus, middle frontal gyrus), 3 ROIs for the SYT (frontal operculum, inferior frontal gyrus, temporal language area) and 2 ROIs for the BST (inferior frontal gyrus, middle frontal gyrus). CONCLUSION: Clinical fMRI using the battery of four tasks is a valid tool for lateralizing language in children, adolescents and young adults. Each task proved to be specifically useful, which confirms that applying different tasks increases the probability of diagnosing language dominance in presurgical candidates.

Age Differences in Decoding Pain from the Facial Expression of Healthy Individuals and Patients with Dementia.

OBJECTIVE: Patients with dementia, whose ability to provide self-report of pain is often impaired, are in crucial need of observers who can detect the patients' pain-indicative behaviors appropriately, to initiate treatment. The facial display of pain promises to be especially informative for that purpose. The age of the observer has been shown to have a critical influence on observational emotion recognition (with age-related decrements in facial emotion recognition) but has not yet been studied as such for pain recognition. METHODS: For that purpose, 24 young (mean age: 24 years) and 22 older (mean age: 70 years) observers watched 120 video clips, showing facial expressions of young and old individuals with and without dementia during slight and moderate noxious stimulation. After each clip, observers were asked to rate how much pain the observed individual might have experienced. RESULTS: Young observers were superior in grading different levels of pain in the observed individuals; furthermore, their ratings corresponded better with the self-ratings of the observed individuals. However, the performance of the older observers was still sufficient as regards the differentiation of different pain levels and prediction of self-report in others. CONCLUSIONS: Age does not only lead to a decline in recognition of facial expressions of emotions but age also affects the quality of observational pain recognition in others. However, given that older observers' performance was only slightly reduced, clearly suggests that older caregivers are surely not at risk of becoming visual agnostic for the pain in others.