Risk of behavioral disturbances in pediatric patients with epilepsy and mild to moderate cognitive impairment: A cross-sectional study.

OBJECTIVE: The aim of the study was to assess whether children and adolescents with epilepsy are at higher risk of behavioral disturbances when they have concomitant cognitive disturbances. METHODS: Behavioral scores were generated using the Child Behavior Checklist (CBCL). Cognitive evaluation was applied by using different age appropriate versions of the Wechsler Intelligence Scale. CBCL scores (total, externalizing, internalizing) were compared between patients with and without intellectual disability (IQ score < 70 and ≥70, respectively). RESULTS: 144 (10.2 mean age, 6.0-17.9 range) patients were recruited for the study. Patients with mild to moderate intellectual disability (full-scale intelligence quotient (FSIQ) < 70) were not at higher risk of behavioral disturbances (total CBCL score ≥ 63) than patients without cognitive impairment. The mean total CBCL score was 62.0 ± 10.6 (range 42.0-83.5, 95% CI 57.9-62.0) and 59.3 ± 10.3 (range 38.0-80.0, CI 57.4-61.2) for patients with FSIQ < 70 and ≥70, respectively. There was no correlation between FSIQ and total CBCL scores. These findings were true for all IQ subcategories. SIGNIFICANCE: Behavioral disturbances among children and adolescents with epilepsy occur despite the presence or absence of intellectual dysfunction with respect to full-scale IQ.

IQ changes after pediatric epilepsy surgery: a systematic review and meta-analysis.

OBJECTIVE: This systematic review aimed to assess the intellectual outcome of children who underwent surgery for epilepsy. METHODS: A systematic review of electronic databases was conducted on December 3, 2021, for PubMed and January 11, 2022, for Web of Science. The review was conducted according to the PRISMA guidelines. The included studies reported on intelligence quotient (IQ) or developmental quotient (DQ) before and after epilepsy surgery in children. Studies were included, if the patients had medically intractable epilepsy and if the study reported mainly on curative surgical procedures. We conducted a random-effects meta-analysis to determine the mean change of IQ/DQ. RESULTS: Fifty-seven studies reporting on a total of 2593 patients met the inclusion criteria. The mean age at surgery was 9.2 years (± 3.44; range 2.4 months-19.81 years). Thirty-eight studies showed IQ/DQ improvement on a group level, 8 yielded stable IQ/DQ, and 19 showed deterioration. Pooled analysis revealed a significant mean gain in FSIQ of + 2.52 FSIQ points (95% CI 1.12-3.91). The pooled mean difference in DQ was + 1.47 (95% CI - 6.5 to 9.5). The pooled mean difference in IQ/DQ was 0.73 (95% CI - 4.8 to 6.2). Mean FSIQ gain was significantly higher in patients who reached seizure freedom (+ 5.58 ± 8.27) than in patients who did not (+ 0.23 ± 5.65). It was also significantly higher in patients who stopped ASM after surgery (+ 6.37 ± 3.80) than in patients who did not (+ 2.01 ± 2.41). Controlled studies showed a better outcome in the surgery group compared to the non-surgery group. There was no correlation between FSIQ change and age at surgery, epilepsy duration to surgery, and preoperative FSIQ. SIGNIFICANCE: The present review indicates that there is a mean gain in FSIQ and DQ in children with medically intractable epilepsy after surgery. The mean gain of 2.52 FSIQ points reflects more likely sustainability of intellectual function rather than improvement after surgery. Seizure-free and ASM-free patients reach higher FSIQ gains. More research is needed to evaluate individual changes after specific surgery types and their effect on long-term follow-up.

Cognitive profiles in pediatric unilobar vs. multilobar epilepsy.

OBJECTIVES: We aimed to determine how cognitive impairment relates to the extent of the presumed epileptogenic zone in pediatric focal epilepsies. We analyzed the cognitive functions in unilobar compared to multilobar focal epilepsy patients that underwent neuropsychological testing at a tertiary epilepsy center. METHODS: We assessed cognitive functions of pediatric focal epilepsy patients with the German version of the Wechsler Intelligence Scales that measures full-scale IQ and subcategories. We assessed differences in IQ and epilepsy-related variables between unilobar and multilobar epilepsy patients. RESULTS: We included 62 patients (37 unilobar, 25 multilobar), aged 10.6 ± 3.7 years. Full-scale IQ values were significantly higher in unilobar (93.6 ± 17.7, 95% CI 87.7-99.6) than in multilobar epilepsy patients (77.3 ± 17.2, 95% CI 69.3-85.0; p = 0.001). In all but one IQ subcategory (working memory), significantly higher values were measured in unilobar than in multilobar epilepsy patients. The proportion of unilobar epilepsy patients with severe cognitive impairment (8.3%) and below-average intelligence (30.5%) was lower compared to multilobar epilepsy patients (47.6% and 61.9%; p = 0.002 and p = 0.021, respectively). Epilepsy onset occurred earlier in multilobar (4.0 years, 95% CI 2.6-5.5, SD ± 3.4 years) than in unilobar epilepsy patients (7.0 years, 95% CI 5.5-8.5, SD ± 4.4 years, p = 0.008). CONCLUSIONS: Pediatric multilobar epilepsy patients face more cognitive issues than unilobar epilepsy patients on average. Our findings should help to identify children and adolescents who are most at risk for impaired cognitive development. A limitation of our study is the simple division into unilobar and multilobar epilepsies, with no specific account being taken of etiology/epilepsy syndrome, which can have a profound effect on cognition.

Cognitive performance and behavior across idiopathic/genetic epilepsies in children and adolescents.

We investigated the cognitive and behavioral profile of three distinct groups of epilepsies with a genetic background for intergroup differences: (1) idiopathic/genetic generalized epilepsies (IGE/GGE group); (2) idiopathic focal epilepsies (IFE group); and (3) epilepsies with proven or strongly suggested monogenic or structural/numeric chromosomal etiology (genetic epilepsies, GE group). Cognitive (total IQ and subcategories) and behavioral parameters (CBCL) were assessed at the tertiary epilepsy center of the University of Munich (Germany). We used ANOVA with post-hoc Bonferroni-correction to explore significant mean differences and Fisher's exact test for significant proportional differences of intelligence impairment and behavioral problems. 126 (56 IGE/GGE, 26 IFE, 44 GE) patients were available. Total IQ was 89.0 ± 15.9 (95% CI 84.5-93.4) for IGE/GGE, 94.8 ± 18.1 (95% CI 87.3-102.3) for IFE and 76.4 ± 22.4 (95% CI 67.6-85.3) for GE (p = 0.001). The same trend was significant for all but one IQ subcategory. The rate of patients with an intelligence impairment (total IQ < 70) was higher for GE (40%) than for IGE/GGE (14%) and for IFE (7%) patients (p = 0.033). There were no significant differences between groups for behavior scores and behavioral problems. This study shows that the current ILAE classification of epilepsies with genetic etiology creates a heterogeneous group of patients with respect to cognitive performance but not behavior. These findings may help in further delineating epilepsies as regards cognitive performance, notwithstanding their closely related etiological classification.

Neural mechanisms for coping with acoustically reduced speech.

In spoken language, reductions of word forms occur regularly and need to be accommodated by the listener. Intriguingly, this accommodation is usually achieved without any apparent effort. The neural bases of this cognitive skill are not yet fully understood. We here presented participants with reduced words that were either preceded by a related or an unrelated visual prime and compared electric brain responses to reduced words with those to their full counterparts. In time-domain, we found a positivity between 400 and 600 ms differing between reduced and full forms. A later positivity distinguished primed and unprimed words and was modulated by reduction. In frequency-domain, alpha suppression was stronger for reduced than for full words. The time- and frequency-domain reduction effects converge towards the view that reduced words draw on attention and memory mechanisms. Our data demonstrate the importance of interactive processing of bottom-up and top-down information for the comprehension of reduced words.

Effect of anticonvulsive treatment on neuropsychological performance in children with BECTS.

INTRODUCTION: Benign epilepsy with centrotemporal spikes (BECTS) is a common epilepsy syndrome in childhood. Besides the occurrence of seizures, mild cognitive impairments and behavioral problems affecting language skills, spatial perception, memory, executive function, and academic achievement might be present. There is no international consensus about the decision whether or not to treat affected children. The influence of treatment on cognitive functions is debated. METHODS: Patients diagnosed with BECTS were assessed in short term auditory memory, long-term verbal memory, intelligence and behavior using the "number recall" test from the Kaufman assessment battery for children, the "verbal learning memory test", the "culture free intelligence test" and the "child behavior checklist" prior to a randomized controlled antiepileptic therapy and after a treatment period of 6 months with either sulthiame or levetiracetam. RESULTS: 43 of 44 randomized patients were analyzed. One patient had to be excluded due to protocol violation. Patients who completed the study showed a non-significant improvement in parent-reported behavioral problems under therapy. Cognitive skills were not affected. CONCLUSION: The present data suggest that antiepileptic drug treatment of children with BECTS with either sulthiame or levetiracetam does not affect cognitive performance. Behavior improved in a subset of patients though not reaching statistical significance.

Mathematical abilities in dyslexic children: a diffusion tensor imaging study.

Dyslexia is characterized by a deficit in language processing which mainly affects word decoding and spelling skills. In addition, children with dyslexia also show problems in mathematics. However, for the latter, the underlying structural correlates have not been investigated. Sixteen children with dyslexia (mean age 9.8 years [0.39]) and 24 typically developing children (mean age 9.9 years [0.29]) group matched for age, gender, IQ, and handedness underwent 3 T MR diffusion tensor imaging as well as cognitive testing. Tract-Based Spatial Statistics were performed to correlate behavioral data with diffusion data. Children with dyslexia performed worse than controls in standardized verbal number tasks, such as arithmetic efficiency tests (addition, subtraction, multiplication, division). In contrast, the two groups did not differ in the nonverbal number line task. Arithmetic efficiency, representing the total score of the four arithmetic tasks, multiplication, and division, correlated with diffusion measures in widespread areas of the white matter, including bilateral superior and inferior longitudinal fasciculi in children with dyslexia compared to controls. Children with dyslexia demonstrated lower performance in verbal number tasks but performed similarly to controls in a nonverbal number task. Further, an association between verbal arithmetic efficiency and diffusion measures was demonstrated in widespread areas of the white matter suggesting compensatory mechanisms in children with dyslexia compared to controls. Taken together, poor fact retrieval in children with dyslexia is likely a consequence of deficits in the language system, which not only affects literacy skills but also impacts on arithmetic skills.

Inequality across consonantal contrasts in speech perception: evidence from mismatch negativity.

The precise structure of speech sound representations is still a matter of debate. In the present neurobiological study, we compared predictions about differential sensitivity to speech contrasts between models that assume full specification of all phonological information in the mental lexicon with those assuming sparse representations (only contrastive or otherwise not predictable information is stored). In a passive oddball paradigm, we studied the contrast sensitivity as reflected in the mismatch negativity (MMN) response to changes in the manner of articulation, as well as place of articulation of consonants in intervocalic positions of nonwords (manner of articulation: [edi ~ eni], [ezi ~ eni]; place of articulation: [edi ~ egi]). Models that assume full specification of all phonological information in the mental lexicon posit equal MMNs within each contrast (symmetric MMNs), that is, changes from standard [edi] to deviant [eni] elicit a similar MMN response as changes from standard [eni] to deviant [edi]. In contrast, models that assume sparse representations predict that only the [ezi] ~ [eni] reversals will evoke symmetric MMNs because of their conflicting fully specified manner features. Asymmetric MMNs are predicted, however, for the reversals of [edi] ~ [eni] and [edi] ~ [egi] because either a manner or place property in each pair is not fully specified in the mental lexicon. Our results show a pattern of symmetric and asymmetric MMNs that is in line with predictions of the featurally underspecified lexicon model that assumes sparse phonological representations. We conclude that the brain refers to underspecified phonological representations during speech perception.

"What you encode is not necessarily what you store": evidence for sparse feature representations from mismatch negativity.

The present study examines whether vowels embedded in complex stimuli may possess underspecified representations in the mental lexicon. The second goal was to assess the possible interference of the lexical status of stimuli under study. Minimal pairs of German nouns differing only in the stressed vowels [e], [ø], and [o], and derived pseudowords, were used to measure the Mismatch Negativity (MMN) in a passive oddball-paradigm. The differing vowels were chosen such that the place of articulation information was conflicting vs. non-conflicting in the framework of models assuming underspecified representations in the mental lexicon (i.e. minimizing featural information by omitting redundant information in order to ensure efficient speech processing), whereas models assuming fully specified phonological representations would predict equal levels of conflict in all possible contrasts. The observed pattern of MMN amplitude differences was in accordance to predictions of models assuming underspecified phonological representations. As the possible interferences by other levels of linguistic processing was demonstrated, it seems favorable to use pseudowords for investigating phonological effects by means of MMN.

Contribution of familiarity and recollection to associative recognition memory: insights from event-related potentials.

Within the dual-process perspective of recognition memory, it has been claimed that familiarity is sufficient to support recognition of single items, but recollection is necessary for associative recognition of item pairs. However, there are some reports suggesting that familiarity might support associative recognition judgments when the items form an easy to access bound representation. In contrast, recollection seems to be required for the recognition of bindings that might be flexibly rearranged in novel situations. We investigated whether both forms of binding are mediated by different mechanisms as reflected by a qualitatively different spatiotemporal eventrelated potential (ERP) pattern. In a recognition memory experiment, subjects gave old/new judgments to words learned by focusing either on interitem associations or on size relation of word triplets. Results revealed higher hit rates in the relational condition as compared to the associative condition. In addition, the proportion of triplets from which all three items were remembered was significantly larger in the relational condition suggesting that memory retrieval in this condition relies primarily on bound representations of word triplets. The ERP revealed a late parietal old/new effect for both conditions, with relational processing resulting in a greater effect. In contrast, an early frontal old/new effect was solely present in the associative condition. Taken together, these data provide evidence that familiarity might support associative recognition if the associated components are coherently encoded into a bound representation. Recollection might foster the recognition of relational bindings among items. This indicates that the contribution of familiarity and recollection to associative recognition depends on the kind of binding operations performed on the items rather than on the single versus multiple item distinction.

Laryngeal elevation achieved by neuromuscular stimulation at rest.

During swallowing, airway protection is achieved in part by laryngeal elevation. Although multiple muscles are normally active during laryngeal elevation, neuromuscular stimulation of select muscles was evaluated to determine which single muscle or muscle pair best elevates the larynx and should be considered during future studies of neuromuscular stimulation in dysphagic patients. Hooked-wire monopolar electrodes were inserted into mylohyoid, thyrohyoid, and geniohyoid muscle regions in 15 healthy men selected for having a highly visible thyroid prominence for videotaping. During trials of single, bilateral, and combined muscle stimulations, thyroid prominence movements were video recorded, digitized, and normalized relative to elevation during a 2-ml water swallow. Individual muscle stimulation induced approximately 30% of the elevation observed during a swallow and approximately 50% of swallow velocity, whereas paired muscle stimulation resulted in approximately 50% of the elevation and approximately 80% of the velocity produced during a swallow. Paired muscle stimulation produced significantly greater elevation than single muscle stimulation and could assist with laryngeal elevation in dysphagic patients with reduced or delayed laryngeal elevation.

The effect of neuromuscular stimulation of the genioglossus on the hypopharyngeal airway.

OBJECTIVES: To determine the effects of neuromuscular stimulation (NS) of the genioglossus muscle on hypopharyngeal airway size. STUDY DESIGN: Fourteen consecutively recruited healthy volunteers underwent percutaneous electrical NS of the genioglossus muscle. METHODS: Bipolar hooked wires were inserted percutaneously into the genioglossus muscle and used for NS. The anterior--posterior diameter of the hypopharynx was measured at the level of the superior edge of the epiglottis at baseline and during NS from recorded video endoscopic examinations. RESULTS: NS of the genioglossus muscle resulted in a significant increase in the diameter of the hypopharyngeal airway (P =.002) compared with baseline, ranging from a 33% to 284% increase in airway diameter. Three of the 14 patients demonstrated modest decreases in airway diameter, likely the result of faulty electrode placement in surrounding tongue retrusive muscles. CONCLUSIONS: NS of the genioglossus muscle was effective in increasing the hypopharyngeal airway and may provide a useful alternative to direct stimulation of the hypoglossal nerve with a nerve cuff electrode in the development of neuroprosthetic treatments for obstructive sleep apnea.