Encephalopathy with continuous spike‐waves during slow‐wave sleep: evolution and prognosis

Encephalopathy with continuous spike‐waves during slow‐wave sleep (CSWS) evolves over time, and three stages can be recognized: before the onset of CSWS, during CSWS, and after the CSWS period. Clinical seizures tend to remit spontaneously around puberty. This pattern is independent of the etiological lesion. The CSWS also disappears in all cases. Focal abnormalities instead, may persist for some time after the disappearance of CSWS. The disappearance of the clinical seizures and CSWS may be simultaneous or seizures may disappear before or after disappearance of the CSWS pattern on the EEG. Electroclinical parameters in the pre‐CSWS period that have been proposed to predict a poor outcome are early‐onset seizures, appearance of new seizures, and a significant increase in seizure frequency. From the electrical point of view, an increase in the frequency of the interictal EEG paroxysms while awake and during sleep and bilateral spike‐and‐wave paroxysms may also be predictive of a poor evolution in CSWS. When CSWS disappears, neurocognitive and behavioral status improve, but in most patients, residual moderate to severe neurocognitive impairments remain. In non‐lesional epilepsy, cognitive recovery after cessation of the CSWS depends on the severity and duration of the initial regression. The duration of the CSWS seems to be the most important predictor of cognitive outcome. Early recognition and effective therapy to reduce the seizures and resolve the CSWS may be crucial to improve long‐term prognosis. Cognitive recovery is observed in patients who respond well to AED treatment and outcome depends on the etiology.     

Cognitive functioning over 3 years in community dwelling older adults with chronic partial epilepsy

Little is known about cognitive functioning of older adults with chronic partial epilepsy. We examined cognitive performance of this epilepsy patient group over 2-3 years. Seventeen older adults with epilepsy and 17 healthy older adults were administered measures of overall cognition and verbal memory at baseline and 2-3 years later. At baseline, older adults with epilepsy performed below controls on overall cognition and verbal memory (p's<0.001). These deficits generally remained stable at follow-up, although executive control appeared to decline (p<0.05). Older adults with epilepsy showed a failure to benefit from practice on a verbal memory measure (p=0.017). Older adults with epilepsy demonstrated cognitive deficits that generally are not progressive. A failure to benefit from repeat exposure to a Delayed Recall task could indicate learning deficits. These patients may also progressively lose executive control, possibly as a result of accelerated aging.     

Executive functions in children with frontal and temporal lobe epilepsy.

Even though frontal lobe epilepsy (FLE) is a relatively common seizure type, no formal psychometric studies of children with FLE have been reported. We compared 12 children with FLE and 15 children with temporal lobe epilepsy (TLE) on neuropsychological tests of attention, memory, executive functioning, and adaptive functioning. The results of these tests indicated that the children with FLE had deficits in planning and executive functions, whereas their verbal and nonverbal memory was intact. The opposite pattern was observed in children with TLE. Measures of executive functioning and impulse control were the best predictors of adaptive functioning. The findings suggest that children with FLE have a pattern of cognitive deficits that differs markedly from the pattern seen in children with TLE. Children with FLE have prominent deficits in executive functioning that appear to be related to poor behavioral adaptation.     

Neuropsychologic effects of frontal lobe epilepsy in children

Most published neuropsychologic studies on frontal lobe epilepsy have been performed on mixed groups of adults and adolescents with epilepsies of varying etiology. The cognitive profile of frontal lobe epilepsy in children has not been defined. The purpose of this study was to assess neuropsychologic performance in children with frontal lobe epilepsy. Intelligence and executive functions were examined in eight children (age 6 7/12 years to 13 11/12 years) with frontal lobe epilepsy. Performance was related to the focus side, seizure frequency, and age of epilepsy onset. Frontal lobe epilepsy was associated with a range of frontal dysfunctions, but IQ was generally spared. Left focus was associated with deficits in categorization, verbal long-term memory, and detailed visuospatial analysis. Frequent seizures correlated with attention difficulties and inability to inhibit impulsive responses. Children whose epilepsy appeared before age 6 years had reduced ability to change behavioral strategies. Frontal epileptic activity alone can cause selective frontal deficits, the severity and nature of which are related to side, seizure frequency, and age of epilepsy onset. These findings require confirmation on larger series of selected children.     

Investigating the ‘latent’ deficit hypothesis: Age at time of head injury, implicit and executive functions and behavioral insight

This study investigated the ‘latent deficit’ hypothesis in two groups of head-injured patients with predominantly frontal lesions, those injured prior to steep morphological and corresponding functional maturational periods for frontal networks (≤age 25), and those injured >28 years. The latent deficit hypothesis proposes that early injuries produce enduring cognitive deficits manifest later in the lifespan with graver consequences for behavior than adult injuries, particularly after frontal pathology (Eslinger, Grattan, Damasio & Damasio, 1992). Implicit and executive deficits both contribute to behavioral insight after frontal head injury (Barker, Andrade, Romanowski, Morton, & Wasti, 2006). On the basis of morphological and behavioral data, we hypothesized that early injury would confer greater vulnerability to impairment on tasks associated with frontal regions than later injury. Patients completed experimental tasks of implicit cognition, executive function measures and the DEX measure of behavioral insight (Behavioral Assessment of the Dysexecutive Syndrome: Wilson, Alderman, Burgess, Emslie, & Evans, 1996). The Early Injury group were more impaired on implicit cognition tasks compared to controls that Late Injury patients. There were no marked group differences on most executive function measures. Executive ability only contributed to behavioral awareness in the Early Injury Group. Findings showed that age at injury moderates the relationship between executive and implicit cognition and behavioral insight and that early injuries result in long-standing deficits to functions associated with frontal regions partially supporting the latent deficit hypothesis.     

The Aspects and Mechanisms of Cognitive Alterations in Epilepsy: The Role of Antiepileptic Medications

Epilepsy is a major health problem. Several studies suggest a significant influence of epilepsy and its treatment on dynamic and functional properties of brain activity. Epilepsy can adversely affect mental development, cognition, and behavior. Epileptic patients may experience reduced intelligence, attention, and problems in memory, language, and frontal executive functions. Neuropsychological, functional, and quantitative neuroimaging studies revealed that epilepsy affect the brain as a whole. Mechanisms of epilepsy‐related cognitive dysfunction are poorly delineated. Cognitive deficits with epilepsy may be transient, persistent, or progressive. Transient disruption of cognitive encoding processes may occur with paroxysmal focal or generalized epileptic discharges, whereas epileptogenesis‐related neuronal plasticity, reorganization, sprouting, and impairment of cellular metabolism are fundamental determinants for progressive cognitive deterioration. Also antiepileptic drugs (AEDs) have differential, reversible, and sometimes cumulative cognitive adverse consequences. AEDs not only reduce neuronal irritability but also may impair neuronal excitability, neurotransmitter release, enzymes, and factors critical for information processing and memory. The present article serves as an overview of recent studies in adult and childhood epilepsy literatures present in PubMed that highlighted cognitive evaluation in epilepsy field (publications till 2008 were checked). We also checked the reference lists of the retrieved studies for additional reports of relevant studies, in addition to our experience in this field. Our search revealed that although the aspects of cognitive dysfunction, risk factors, and consequences have been explored in many studies; however, the mechanisms of contribution of epilepsy‐related variables, including AEDs, to patients' cognition are largely unexplored. In this review, we discussed the differential effect of AEDs in mature and immature brains and the known mechanisms underlying epilepsy and AEDs adverse effects on cognition. The nature, timing, course, and mechanisms of cognitive alteration with epilepsy and its medications are of considerable clinical and research implications.     

Anatomy of executive deficit following ruptured anterior communicating artery aneurysm

Background and purpose: To evaluate behavioral and cognitive deficits following anterior communicating artery aneurysm rupture and determine critical lesion locations. Methods: We investigated 74 patients with standardized cognitive tests and behavioral inventory. Two examiners rated MRI signal abnormalities in 51 predetermined regions of interest. Classification tree analysis was used to select regions associated with each cognitive deficit. Results: Eleven patients presented behavioral executive deficits and 10 had cognitive executive deficit. Their presence depended on left hemisphere lesions only: (i) ventral striatum lesion was associated with behavioral executive deficit (P = 0.04), reduction of activities (P = 0.01), and hyperactivity (P = 0.02); (ii) superior frontal gyrus lesion, with cognitive executive deficit (P = 0.01), action initiation deficit (P = 0.02), and rule deduction deficit (P = 0.02); (iii) anterior half of centrum semiovale lesion, with Stroop inhibition deficit (P = 0.02); (iv) medial superior and middle frontal gyri lesions, with task coordination deficit (P = 0.01); and (v) middle frontal gyrus lesion, with words generation deficit (P = 0.02). Conclusion: This study supports that (i) cognitive executive deficits depend mostly on lateral prefrontal lesions, (ii) with locations varying according to executive process, and (iii) behavioral executive deficits are mainly due to left ventral striatum lesion in post‐aneurysmal damage.     

Impact of severe epilepsy on development: Recovery potential after successful early epilepsy surgery

Purpose: Epilepsy surgery in young children with focal lesions offers a unique opportunity to study the impact of severe seizures on cognitive development during a period of maximal brain plasticity, if immediate control can be obtained. We studied 11 children with early refractory epilepsy (median onset, 7.5 months) due to focal lesion who were rendered seizure‐free after surgery performed before the age of 6 years. Methods: The children were followed prospectively for a median of 5 years with serial neuropsychological assessments correlated with electroencephalography (EEG) and surgery‐related variables. Results: Short‐term follow‐up revealed rapid cognitive gains corresponding to cessation of intense and propagated epileptic activity [two with early catastrophic epilepsy; two with regression and continuous spike‐waves during sleep (CSWS) or frontal seizures]; unchanged or slowed velocity of progress in six children (five with complex partial seizures and frontal or temporal cortical malformations). Longer‐term follow‐up showed stabilization of cognitive levels in the impaired range in most children and slow progress up to borderline level in two with initial gains. Discussion: Cessation of epileptic activity after early surgery can be followed by substantial cognitive gains, but not in all children. In the short term, lack of catch‐up may be explained by loss of retained function in the removed epileptogenic area; in the longer term, by decreased intellectual potential of genetic origin, irreversible epileptic damage to neural networks supporting cognitive functions, or reorganization plasticity after early focal lesions. Cognitive recovery has to be considered as a “bonus,” which can be predicted in some specific circumstances.     

Mesial temporal lobe epilepsy impairs advanced social cognition

PURPOSE: Although memory, language, and executive functions have been extensively studied in patients with mesial temporal lobe epilepsy (MTLE), investigations into advanced social cognitive abilities have been neglected. In the present study, we investigated the ability to detect social faux pas and studied possible mediating clinical and demographic variables in patients with MTLE compared with patients with an epilepsy not originating within the MTLE and healthy controls. METHODS: The 27 MTLE patients (16 were investigated pre- and 11 postoperatively), 27 patients with an extramesiotemporal epilepsy (except frontal lobe epilepsy), and 12 healthy controls performed a shortened version of the faux-pas test. Additionally, we used standardized tests to measure intelligence. Only patients with intact reading-comprehension abilities were included in the study. RESULTS: MTLE patients, both pre- and postoperative, performed the faux-pas test significantly worse than patients with extramesiotemporal lobe epilepsy and healthy controls. The latter two groups showed comparable performance. No statistical association was found between the MTLE patients' deficit in recognizing a faux pas and the variables IQ, age, age at seizure onset, and duration of epilepsy. CONCLUSIONS: We report for the first time that patients with MTLE are specifically impaired in recognizing faux pas, suggesting that MTLE as such is a specific etiology of deficits in higher-order social cognition.     

Emotion recognition, 'theory of mind,' and social behavior in schizophrenia

Several studies have demonstrated that patients with schizophrenia are impaired in recognizing emotions from facial expressions and in appreciating other people's mental states--the latter commonly referred to as 'theory of mind.' The question as to how social cognitive skills relate to patients' actual social behavior is, however, largely unanswered. This study examined emotion recognition, 'theory of mind,' and social behavior in schizophrenia. Emotion recognition, 'theory of mind,' executive functioning, 'crystallized' verbal intelligence, psychopathology, and social behavior were assessed in patients with schizophrenia compared with a healthy control group. Patients were significantly impaired on all tasks involving executive functioning, emotion recognition, and 'theory of mind.' Impaired executive functioning did, however, only partially account for the deficits in social perception and social cognition. Social perception and cognition in schizophrenia predicted the odds of being a patient significantly better than nonsocial cognition. Severe social behavioral abnormalities were linked to the duration of the illness, and even more so to 'theory of mind' deficits. Considering impaired social perception and social cognition significantly contributes to the understanding of social behavioral problems in schizophrenia.     

Cognitive outcome of parietooccipital resection in children with epilepsy

Purpose: We followed the neuropsychological development of five children who underwent unilateral neurosurgery of the occipitoparietal lobes as a treatment for epilepsy caused by a developmental lesion (cortical dysplasia). Methods: The follow‐up period ranged from 3–7 years postsurgery. Results: Two participants had a verbal intelligence quotient (IQ) >100 and three had a verbal IQ between 65 and 80. All five children had abnormal nonverbal IQ and exhibited deficits related to visual attention, object recognition, and praxis. Nevertheless, our results suggest that brain plasticity after parietooccipital epilepsy surgery in young children allows for a schooling level of cognitive skills such as reading and arithmetic. Discussion: Although recovery for visual perceptual cognition was more limited than for verbal functions, long‐term neuropsychological outcomes showed that early surgery for epilepsy offers the possibility of optimizing cognitive outcomes in children with posterior intractable epilepsies.     

Unilateral frontal lobe epilepsy affects executive functions in children

Abstract Very few studies to date have investigated the neuropsychological changes detectable in children suffering from frontal lobe epilepsy (FLE). The aim of the present study was to assess the effects of FLE on cognitive and executive functions in childhood. The sample includes 17 children with a frontal epileptogenic focus (10 right and 7 left), with no evidence of anatomical brain damage. These subjects were assessed by means of a battery of tests to investigate executive functioning. The results emphasised the presence of selective impairments of frontal lobe functions without evidence of deficits in global intellectual functioning. No side-specific deficits were detected, while an earlier onset of epilepsy and the duration of the disorder, but not the seizures frequency, were found to correspond with more severe deficits in some specific frontal lobe functions.     

Postsurgical outcome in pediatric patients with epilepsy: a comparison of patients with intellectual disabilities, subaverage intelligence, and average-range intelligence

PURPOSE: Intellectual disabilities are often associated with bilateral or diffuse morphologic brain damage. The chances of becoming seizure free after focal surgery are therefore considered to be worse in patients with intellectual disabilities. The risk of postoperative cognitive deficits could increase because diffuse brain damage lowers the patient's ability to compensate for surgically induced deficits. Several studies in adult patients have indicated that IQ alone is not a good predictor of postoperative cognitive and seizure outcome. Our study evaluated this subject in children and adolescents. METHODS: Pediatric patients with intellectual disabilities (IQ < or = 70), subaverage intelligence (IQ between 71 and 85), or average-range intelligence (IQ > 85) were matched according to several clinical and etiologic criteria to determine the influence of IQ (N = 66). RESULTS: No dependency of seizure outcome, postoperative cognitive development, and behavioral outcome on the IQ level was found. All groups slightly improved in attention while memory functions tended to decrease and executive functions were stable. School placement remained unchanged for the majority of patients. Between 67 and 78% were seizure free 1 year after surgery (Engel outcome class I). CONCLUSIONS: IQ alone is not a good predictor of postoperative outcome in pediatric patients with epilepsy. As with patients of average-range intelligence, the decision to operate on patients with a low level of intelligence should depend on the results of the presurgical diagnostics. If the results of the neuropsychological examination indicate diffuse functional impairment, this should not hinder further steps, if all other findings are consistent.     

Elucidating the contributions of processing speed, executive ability, and frontal lobe volume to normal age-related differences in fluid intelligence.

One theory of normal cognitive aging asserts that decreases in simple processing speed mediate the age-related decline of fluid intelligence. Another possibility is that age-related atrophic changes in frontal brain structures undermine the functioning of executive abilities, thereby producing the same decline. In this study, we used principal components analysis to derive a measure of fluid-spatial intelligence in 197 normal adults between 20 and 92 years of age. Measures of perceptual comparison speed, working memory, and executive ability, as well as regional brain volumes based on high resolution magnetic resonance imaging were obtained from a subsample of 112 participants. We then conducted a series of hierarchical multiple regression analyses to test whether (1) the processing speed theory, (2) frontal-executive theory, or (3) some combination of these best accounted for age-related variation in fluid intelligence. The results showed that perceptual comparison speed, executive ability, and frontal lobe volume each made significant contributions to a regression equation that explained 57% of the variance in fluid intelligence. These findings suggest that both the processing speed and frontal-executive theory of cognitive aging are partially correct and complement one another.     

Neuropsychological Findings in Rolandic Epilepsy and Landau-Kleffner Syndrome

Summary:  In an attempt to correlate neuropsychological deficits and various neurophysiological aspects of focal epileptic activity in benign childhood epilepsy, we have reviewed the findings of a longitudinal group study of benign childhood epilepsy with centrotemporal spikes (BCECTS) and several case studies of continuous spike-waves during slow sleep syndrome (CSWS). We first distinguish the temporary neuropsychological impairments often observed in the natural history of BCECTS from the more long-lasting and more specific neuropsychological deficits associated with CSWS, of which the Landau-Kleffner syndrome (LKS) is the most studied clinical form. A series of metabolic findings from ¹⁸FDG-PET studies in BCECTS and CSWS children have shown that specific cognitive impairment is related to increased glucose uptake in cortical areas restricted to the associative cortex coincident with the focus of spike-wave discharges. From recent functional neuroimaging data of three patients recovered from LKS, we address the issue of the pathophysiology of cognitive impairment persisting after complete recovery of epilepsy. Finally, we discuss the reliability of the study of mismatch negativity to address the issue of the early effect of interictal discharges in typical and atypical BCECTS on the auditory cortex and the development of speech processing essential to verbal learning.     

Levetiracetam efficacy in epileptic syndromes with continuous spikes and waves during slow sleep: experience in 12 cases

PURPOSE: To assess the add-on efficacy of levetiracetam on the EEG, behavior, and cognition of children with continuous spikes and waves during slow sleep (CSWS). METHODS: Charts of children with behavioral and/or cognitive deterioration associated with CSWS who received levetiracetam at 50 mg/kg/day as add-on treatment were retrospectively reviewed. Awake and sleep EEG recordings and detailed neuropsychological and behavioral assessments were available at baseline and 2 months after levetiracetam initiation. In children showing clinical and/or electrophysiological improvement after 2 months, levetiracetam was continued with a new evaluation at 1 year. RESULTS: Twelve patients were included (9 cryptogenic and 3 symptomatic cases). Seven patients (58.3%) showed improvement of EEG record. Among these seven patients, neuropsychological evaluation was improved in three, and in the other four patients, not testable because of severe cognitive impairment, behavior was improved. Two patients improved in neuropsychological evaluation despite the lack of EEG improvement. Eight patients (66.6%) continued levetiracetam treatment after 2 months. After 1 year, four patients were still on levetiracetam, two because sustained effect on EEG and behavior and the two others because improvement in neuropsychological testing despite unchanged EEG. Levetiracetam was discontinued in the other four patients because of neuropsychological or behavioral deterioration associated with CSWS pattern, between 9 and 11 months after treatment initiation. CONCLUSIONS: This retrospective study suggests that levetiracetam has a positive effect on the EEG, the behavior, and the cognition of patients with epilepsy and CSWS. Additional studies are warranted in order to assess the place of this drug in these epileptic conditions.     

Growing up with epilepsy: a two-year investigation of cognitive development in children with new onset epilepsy

Purpose: To characterize patterns and determinants of normal and abnormal cognitive development in children with new onset epilepsy compared to healthy controls. Methods: Longitudinal (2‐year) cognitive growth was examined in 100 children, age 8–18 years, including healthy controls (n = 48) and children with new onset epilepsy (n = 52). Cognitive maturation was examined as a function of the presence/absence of two neurobehavioral comorbitiies (attention deficit hyperactivity disorder and/or academic problems) identified at the time of epilepsy diagnosis. Groups were compared across a comprehensive neuropsychological battery assessing intelligence, academic achievement, language, memory, executive function, and psychomotor speed. Results: Children with new onset epilepsy without neurobehavioral comorbidities were comparable to healthy controls at baseline, rate of cognitive development, and follow‐up assessment across all neuropsychological domains. In contrast, the presence of neurobehavioral comorbidities was associated with significantly worse baseline and prospective cognitive trajectories across all cognitive  domains, especially executive functions. Conclusion: The presence of neurobehavioral comorbidities at the time of epilepsy onset is a major marker of abnormal cognitive development both prior to and after the onset of epilepsy.     

Cognitive decline in severe intractable epilepsy

PURPOSE: To explore the relation between seizure-related variables and cognitive change in patients with severe intractable epilepsy. METHODS: A retrospective analysis of data from 136 patients who had undergone a cognitive assessment on two occasions at an interval of > or =10 years. Cognitive measures included tests of memory and executive skills in addition to intelligence quotients (IQ). Details were available regarding seizure type and frequency in the intertest interval. RESULTS: Cognitive decline was severe and occurred across a wide range of cognitive functions. The frequency of generalised tonic-clonic seizures was the strongest predictor of decline. Complex partial seizure frequency was associated with a decline in memory and executive skills but not in IQ. Seizure-related head injuries and advancing age carried a poor cognitive prognosis, whereas periods of remission were associated with a better cognitive outcome. Early age at onset was not implicated, and duration of epilepsy was a much less potent predictor of cognitive decline than has been reported in cross-sectional studies. No evidence indicated that a higher level of cognitive function protected against cognitive decline. CONCLUSIONS: Our findings, together with those from animal studies and surgically treated patients, suggest that seizures can have a direct adverse effect on cognition and that good seizure control even after years of intractability can have a beneficial impact on cognitive prognosis. This study was based on individuals who merited two cognitive assessments > or =10 years apart and hence is biased in favor of those with the most severe forms of refractory epilepsy and those with decline.     

Long‐term cognitive follow‐up of Parkinson's disease patients with impulse control disorders

This study investigated cognitive functions in Parkinson's disease (PD) patients with impulse control disorders (ICDs) and aimed to identify possible predictors of behavioral outcome. In this longitudinal cohort study, 40 PD outpatients with ICDs and 40 without, were matched for sex, age at PD onset, age and disease duration at cognitive assessment. All patients had two neuropsychological assessments at least 2 years apart (mean, 3.5 years). Multivariate logistic regression analysis was performed to identify predictors of ICDs remission at follow‐up. The PD patients with and without ICDs had overall comparable cognitive performance at baseline. When evaluating changes between baseline and follow‐up, we found significant group × time interactions in several frontal lobe–related tests, with the ICDs group showing a less pronounced worsening over time. ICDs remission was associated with better performance at baseline in working memory–related tasks, such as digit span (odds ratio [OR] = 2.69 [95% confidence interval (CI), 1.09‐6.66]) and attentive matrices (OR=1.19 [95%CI, 1.03‐1.37]). ICDs remitters and non‐remitters had no remarkable differences in baseline PD‐related features and therapy management strategies (including the extent of dopamine agonist dose reduction). In conclusion, ICDs in PD patients are not related to greater cognitive impairment or executive dysfunction, but rather show relatively lower cognitive decline over time. The impaired top‐down inhibitory control characterizing ICDs is likely attributable to a drug‐induced overstimulation of relatively preserved prefrontal cognitive functions. Full behavioral remission in the long term was predicted by better working memory abilities. © 2015 International Parkinson and Movement Disorder Society     

Cognitive and behavioral complications of frontal lobe epilepsy in children: a review of the literature

Frontal lobe epilepsy (FLE) is considered the second most common type of the localization-related epilepsies of childhood. Still, the etiology of FLE in children, its impact on cognitive functioning and behavior, as well as the response to antiepileptic drug treatment in children has not been sufficiently studied. This review focuses on these aspects of FLE in childhood, and reveals that FLE in childhood is most often cryptogenic, and impacts on a broad range of cognitive functions. The nature and severity of cognitive deficits are highly variable, although impaired attention and executive functions are most frequent. Young age at seizure onset is the only potential risk factor for poor cognitive outcome that has been consistently reported. The behavioral disturbances associated with FLE are also highly variable, although attention deficit/hyperactivity disorder seems most frequent. In 40% of children with FLE satisfactory seizure control could not be achieved. This is a higher percentage than reported for the general population of children with epilepsy. Therefore, pediatric FLE, even if cryptogenic in nature, is frequently complicated by impairment of cognitive function, behavioral disturbances, and therapy-resistance. Given the impact of these complications, there is a need for studies of the etiology of frontal lobe epilepsy-associated cognitive and behavioral disturbances, as well as pharmacotherapy-resistance.