Cognitive Impairment in Juvenile Myoclonic Epilepsy

Background and purpose

Cognitive impairments are frequent consequences of epilepsy, with intellectual ability reportedly being lower in patients with idiopathic generalized epilepsies than in the general population. However, neuropsychological investigations have been rarely performed in patients with juvenile myoclonic epilepsy (JME). We aimed to quantify the cognitive function in JME patients using various neuropsychological tests.

Methods

We compared cognitive function in 27 JME patients with that in 27 healthy volunteers using tests examining cognitive performance, such as the verbal and visual memory, frontal function, attention, IQ score, and mood. In the JME group, we examined risk factors for cognitive function such as age, sex, family history, education level, age at seizure onset, seizure frequency, EEG abnormality, disease duration, and previous intake of antiepileptic drugs.

Results

Verbal learning was significantly lower in JME patients than in controls, and attention and verbal fluency were impaired in JME patients compared with controls. However, general intellectual ability and mood did not differ between the groups. Early onset of seizure and long duration of disease were closely related to impaired cognitive function.

Conclusions

JME patients may exhibit impaired cognitive function, in terms of memory and execution, despite having normal intelligence and mood.     

Neuropsychiatric profiles of patients with juvenile myoclonic epilepsy treated with valproate or topiramate

In this cross-sectional study, the neuropsychiatric profiles of 42 patients with juvenile myoclonic epilepsy (JME) who were treated with valproate (VPA) or topiramate (TPM) in monotherapy were compared with the aim of verifying the relationship between cognitive dysfunction, psychiatric disorders, and factors related to epilepsy. Patients with JME taking VPA 500-1750 mg/day or TPM 50-175 mg/day were selected. For all patients, psychiatric profiles were evaluated with the Scheduled Clinical Interview, axes I and II (SCID I and SCID II), or the Brazilian version of the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS-PL). Neuropsychological measures included intellectual functions, attention, memory, executive functions, and language. Patients taking TPM exhibited worse neuropsychological performance on attention, short-term memory, processing speed, and verbal fluency functions related to frontal lobes, which may be dysfunctional in JME. Anxiety disorders were associated with lack of seizure control and having had more than 20 lifetime generalized tonic-clonic seizures.     

Cognitive changes in people with temporal lobe epilepsy over a 13-year period

ObjectivesThe aims of our study were to evaluate cognitive decline in people with temporal lobe epilepsy over a period of 13 years and to determine what clinical and treatment characteristics may have been associated with these.Materials and methodsThirty-three individuals with temporal lobe epilepsy underwent the same neuropsychological assessment of verbal and nonverbal memory, attention, and executive functions using the same cognitive test battery as one used 13 years ago. Long-term verbal and nonverbal memory was tested four weeks later. Results were compared with those carried out 13 years earlier.ResultsThere was no significant change in verbal and verbal–logical memory tests; however, nonverbal memory worsened significantly. Long-term verbal memory declined for 21.9% of participants, long-term verbal–logical memory for 34.4%, and long-term nonverbal memory for 56.3%. Worsening of working verbal and verbal–logical memory was associated with longer epilepsy duration and lower levels of patients' education; worsening of verbal delayed recall and long-term verbal–logical memory was associated with higher seizure frequency. Decline in long-term nonverbal memory had significant association with a longer duration of epilepsy. The worsening of reaction and attention inversely correlated with the symptoms of depression.ConclusionOver a 13-year period, cognitive functions did not change significantly. Good seizure control and reduced symptoms of depression in this sample of people with temporal lobe epilepsy were associated with better cognitive functioning. The predictors of change of cognitive functions could be complex and require further study.     

Cognitive phenotype of juvenile absence epilepsy: An investigation of patients and unaffected siblings

Objective

The cognitive profile of juvenile absence epilepsy (JAE) remains largely uncharacterized. This study aimed to: (1) elucidate the neuropsychological profile of JAE; (2) identify familial cognitive traits by investigating unaffected JAE siblings; (3) establish the clinical meaningfulness of JAE-associated cognitive traits; (4) determine whether cognitive traits across the idiopathic generalized epilepsy (IGE) spectrum are shared or syndrome-specific, by comparing JAE to juvenile myoclonic epilepsy (JME); and (5) identify relationships between cognitive abilities and clinical characteristics.

Methods

We investigated 123 participants—23 patients with JAE, 16 unaffected siblings of JAE patients, 45 healthy controls, and 39 patients with JME—who underwent a comprehensive neuropsychological test battery including measures within four cognitive domains: attention/psychomotor speed, language, memory, and executive function. We correlated clinical measures with cognitive performance data to decode effects of age at onset and duration of epilepsy.

Results

Cognitive performance in individuals with JAE was reduced compared to controls across attention/psychomotor speed, language, and executive function domains; those with ongoing seizures additionally showed lower memory scores. Patients with JAE and their unaffected siblings had similar language impairment compared to controls. Individuals with JME had worse response inhibition than those with JAE. Across all patients, those with older age at onset had better attention/psychomotor speed performance.

Significance

JAE is associated with wide-ranging cognitive difficulties that encompass domains reliant on frontal lobe processing, including language, attention, and executive function. JAE siblings share impairment with patients on linguistic measures, indicative of a familial trait. Executive function subdomains may be differentially affected across the IGE spectrum. Cognitive abilities are detrimentally modulated by an early age at seizure onset.     

Cognitive function in juvenile myoclonic epilepsy

In this study, we examined 35 patients with juvenile myoclonic epilepsy (JME) and 35 healthy volunteers. We used tests of cognitive performance (mini mental state examination, verbal and visual memory, visuospatial, frontal function, attention). In the JME group, we examined age, sex, family history, education level, age of seizure onset, seizure types, characteristics of EEG, duration of the therapy, drug dose and level, and verbal IQ level. Additionally, patients initially diagnosed as JME and patients who were initially under inappropriate drug therapy because of misdiagnosis were compared. As a result, we found statistically significant differences between JME patients and the control group with respect to verbal and visual memory. Furthermore, JME patients had impaired frontal and visuospatial function compared with the control group. We detected negative effects of younger age, family history, and absence seizures on cognitive function in JME patients.     

Delineating behavioral and cognitive phenotypes in juvenile myoclonic epilepsy: Are we missing the forest for the trees?

IntroductionPatients with juvenile myoclonic epilepsy (JME) have executive dysfunction and impulsive traits. There are lines of evidence that JME is a heterogeneous epilepsy syndrome considering outcome. In this study, we aimed to analyze this heterogeneity beyond seizure control. The objective was to identify whether the pattern of cognitive dysfunction and impulse control is also heterogeneous, in an attempt to establish possible differences in patients with easy- and hard-to-control epilepsies.MethodsEssentially, 57 patients with JME were compared with 44 controls. Patients and controls were assessed with a neuropsychological battery for executive, attention, and memory functions. The expression of impulsive traits was evaluated with the Temperament and Character Inventory — novelty seeking domain. Then, patients were categorized according to seizure control as having easy- and hard-to-control JME.ResultsPatients with hard-to-control JME showed worse performance in 12 out of 25 neuropsychological tests than those with easy-to-control JME. Patients with hard-to-control JME also demonstrated significantly higher scores in novelty seeking — subfactor impulsiveness (p = 0.002).SignificanceOur study demonstrated the existence of distinct or more severe cognitive and psychiatric profiles in a subset of patients with JME. Patients with treatment-refractory seizures seem to present a broader impairment related to both cognitive deficits and impulsive traits. These findings suggest that patients with JME are not equally compromised by executive and memory deficits or dysfunction, neither by their impulsive traits. Thus, there is a need for a better characterization of patients with JME to include diverse phenotypes since our results suggest a possible existence of distinct groups of patients with JME.     

Evaluation of cognitive functions of juvenile myoclonic epileptic patients by magnetic resonance spectroscopy and neuropsychiatric cognitive tests concurrently

Our aim in this research is investigating the hypothesis of biochemical changes in frontal cortex and thalamocortical pathways in juvenile myoclonic epilepsy (JME) and the interaction between the biochemical changes and cortical functions. Magnetic resonance spectroscopy (MRS) was applied to 20 JME patients and 20 controls for measuring N-acetyl aspartate (NAA), N-acetyl aspartate to creatine ratio (NAA/Cr), Glutamine and Glutamate (GLX), Glutamine–Glutamate to creatine (GLX/Cr), Choline containing compounds (Cho) and Choline to creatine (Cho/Cr) levels. Neuropsychological cognitive tests for linguistic and visual attention, linguistic and visual memory, visuospatial and executive functions were applied to all participants. NAA and NAA/Cr concentrations were found lower in bilateral frontal and thalamic regions in JME group as compared with the control group (p < 0.05). There was no difference in frontal and thalamic GLX, GLX/Cr, Cho, Cho/Cr levels in between JME patients and controls (p > 0.05). JME patients were found more unsuccessful than the controls in attention, memory, visuospatial function, verbal fluency, Trail B test and executive functions, stroop test, clock drawing test and Trail A test (p < 0.05). Prefrontal NAA/Cr level was positively related to visual attention, memory, stroop test and thalamic NAA/Cr level was positively related to linguistic memory and Wisconsin card sorting test in JME patients. This research highlights regional brain changes and cognitive decline in JME patients and suggests that MRS may be a sensitive technique for showing subclinical cognitive changes.     

Juvenile myoclonic epilepsy: The impact of clinical variables and psychiatric disorders on executive profile assessed with a comprehensive neuropsychological battery

Executive dysfunction is reported in juvenile myoclonic epilepsy (JME). However, batteries employed in previous studies included no more than three tests of executive function. In this study, we aimed to assess executive and attentional functions in JME using a comprehensive battery of eight tests (encompassing fifteen subtests). We also evaluated neuropsychological profiles using a clinical criterion of severity and correlated these findings with epilepsy clinical variables and the presence of psychiatric disorders. We prospectively evaluated 42 patients with JME and a matched control group with Digit Span tests (forward and backward), Stroop Color-Word Test, Trail Making Test, Wisconsin Card-Sorting Test, Matching Familiar Figures Test and Word Fluency Test. We estimated IQ with the Matrix Reasoning and Vocabulary subtests of the Wechsler Abbreviated Intelligence Scale. The patients with JME showed specific deficits in working memory, inhibitory control, concept formation, goal maintenance, mental flexibility, and verbal fluency. We observed attentional deficits in processes such as alertness and attention span and those requiring sustained and divided attention. We found that 83.33% of the patients had moderate or severe executive dysfunction. In addition, attentional and executive impairment was correlated with higher frequency of seizures and the presence of psychiatric disorders. Furthermore, executive dysfunction correlated with a longer duration of epilepsy. Our findings indicate the need for comprehensive neuropsychological batteries in patients with JME, in order to provide a more extensive evaluation of attentional and executive functions and to show that some relevant deficits have been overlooked.     

Cognitive decline in temporal lobe epilepsy due to unilateral hippocampal sclerosis

ObjectiveWe assessed the cognitive performance of patients with temporal lobe epilepsy (TLE) caused by unilateral hippocampal sclerosis (HS), in comparison with that of matched, healthy controls. We report the relationship between cognitive measures and duration of epilepsy, correlating with hippocampal volumes, and the impact of educational level on cognitive decline.MethodsThis study involved 61 outpatients (40 with ⩽8 years and 21 with >8 years of formal education) with unilateral HS and 61 controls. Volumetric MRI was performed on all patients and 10 controls. The results (mean, SD) of the neuropsychological tests of healthy subjects and patients were compared using the Student t and Mann–Whitney tests.ResultsPatients performed worse than controls in the neuropsychological evaluation. When adjusted z scores were used to calculate the impairment index, patients had a greater percentage of abnormal tests compared with controls. The cognitive decline, assessed through the impairment index, correlated with duration of epilepsy. Higher level of education did not protect against this decline, thus not supporting the hypothesis of cerebral reserve in this population. A significant correlation between hippocampal volumetric measures and duration of epilepsy was observed only in patients with left HS.ConclusionPatients with TLE caused by HS present with cognitive morbidity that extends beyond memory deficits. Cognitive decline is associated with duration of epilepsy, and in patients with left-sided HS, duration may correlate with volumetric hippocampal loss.     

Motor and cognitive functions in newly diagnosed adult seizure patients before antiepileptic medication

OBJECTIVE: Motor and cognitive functions in patients with partial or generalized onset of seizures were evaluated prior to the administration of antiepileptic medication. MATERIAL AND METHODS: Motor function, attention and memory of 52 consecutive newly diagnosed adult patients with partial or generalized seizures were assessed with neuropsychological tests. RESULTS: Patients with partial onset of seizures did not differ from patients with generalized seizures in tests of motor function or attention, nor in tests of learning and memory. Compared to controls patients with epilepsy performed significantly worse on visual motor tasks, mental flexibility and in delayed visual memory. Within the patient group as a whole lower education, higher age and symptomatic epilepsy with more abnormal CT scan findings tended to associate with worse performance in tests of concentration and mental flexibility and tests of memory. CONCLUSION: These findings indicate that newly diagnosed adult patients with partial or generalized onset of seizures prior to treatment with antiepileptic medication experience some problems in visual motor tasks, mental flexibility and memory even without the numerous risk factors for cognitive deficits in epilepsy. In newly diagnosed patients with epilepsy as a whole symptomatic etiology was associated with somewhat more pronounced cognitive problems.     

癫(癎)患者认知功能特点的研究

目的:研究癫(EP)患者认知功能的特点及其影响因素。方法:采用听觉词语测验、逻辑记忆测验、数字符号转换测验、Stoop字色干扰测验、连线测验、言语流畅性测验、Rey-Osterrieth复杂图片测验及Boston命名测验对166例EP患者进行认知评定。结果:EP患者存在广泛的认知损害,包括言语记忆、情景记忆、视觉空间结构记忆、词语学习能力、注意力、抗干扰能力、精神运动速度及言语命名功能等方面,以词语延迟回忆、注意力及精神运动速度损害最为明显。而未经药物干预的新诊断EP患者已存在除视觉空间记忆、注意力及抗干扰能力外的上述认知功能的损害,以词语延迟回忆最为明显。随访病例与新诊断病例的区别在于,前者在抗干扰能力及精神运动速度方面损害更明显。结论:新诊断EP组以及随访EP组病例在多项神经心理学测验中得分均低于正常对照组,两组之间差异有统计学意义。     

Neuropsychological study of patients with obsessive-compulsive disorder and their parents in China: searching for potential endophenotypes

Objective The existence of neuropsychological deficits has been implicated in obsessive-compulsive disorder (OCD), particularly memory, attention, and executive functions. However, few studies have focused on neuropsychological deficits in the relatives of OCD patients. The aim of this study was to investigate cognitive deficits in OCD patients and their parents. Methods Forty patients with OCD, 48 parents of these patients, and 87 healthy controls completed a neuropsychological testing battery. Results Both OCD patients and their parents showed impairments in delayed verbal memory and delayed visual memory. Furthermore, they performed worse than healthy controls in problem-solving ability. Conclusion Our study demonstrated familial aggregation of delayed memory deficits and impaired problem-solving ability, which may be the potential neuropsychological endophenotypes of hereditary susceptibility to OCD.     

Executive dysfunction in spinocerebellar ataxia type 1.

Fourteen patients with spinocerebellar ataxia 1 (SCA1) and 11 controls with similar mean age and IQ estimates were submitted to a neuropsychological test battery comprising tests for IQ, attention, verbal and visuospatial memory as well as executive functions. Neuropsychological assessment yielded verbal memory and executive dysfunction while tests of visuospatial memory and attention were not significantly impaired in SCA1 as compared to controls. Test performance was neither related to the repeat length, the age of onset nor the disease duration. The profile of cognitive impairment in SCA1 with prominent executive dysfunction corresponds to the concept of "frontal-subcortical" dementia that is likely to be contingent upon disruption of a cerebrocerebellar circuitry that consists of afferent and efferent connections between the prefrontal cortex and the cerebellum.     

The perception of memory failures in patients with epilepsy

The aim of the study is to evaluate the correlation between subjective memory complaints and neuropsychological tests in the epilepsy population. We administered a Self Report Memory Questionnaire, based on possible everyday memory failures, two questionnaires on anxiety and depression and a battery of cognitive tests to 150 patients with epilepsy (n=100 with partial epilepsy, n=50 with idiopathic generalized epilepsy) and a control group (n=50). A discrepancy between the results of the memory questionnaire and the cognitive tests was found in the epilepsy patients: the Self Report Memory Questionnaire did not show any correlation with the psychological tests. The same discrepancy was not seen in the controls, where the memory questionnaire was related to two verbal memory tests. Furthermore, patients with epilepsy reported greater difficulties on the Self Report Memory Questionnaire than the controls (P < 0.05). It appeared that the tendency to overstate memory problems was mainly related to anxiety and depression, but was not connected with the type of epilepsy, nor with its duration (in years). Seizure frequency, on the other hand, seemed to greatly influence mood, which in turn is probably affect subjective memory perception.     

癫(癎)患者认知功能损害及其影响因素分析

目的采用神经心理学方法研究癫患者认知功能受损情况及其影响因素。方法对67例癫患者和63例年龄、性别、学历、文化背景与癫患者相匹配的健康志愿者进行韦氏成人智力量表(WAIS)检测。结果癫患者的FIQ较对照组显著减低,有40%的癫患者智商低于正常,存在认知功能损害。颞叶癫、部分性发作、发作频率和文化程度对FIQ值有显著性意义。结论癫患者确实存在认知功能障碍,且颞叶癫痫间患者认知功能受损更为明显。     

Intellectual Disability and Psychotic Disorders of Adult Epilepsy

Summary:  Purpose: To investigate the prevalence, psychopathology, and cognitive functions associated with psychotic disorders among adult epilepsy patients with intellectual disability (ID) based on a multicenter study in Japan.
Methods: The study was divided into three phases; a prevalence study of psychotic disorders among new referrals of epilepsy, a polydiagnostic comparative study of patients with psychotic epilepsy and those with schizophrenia, and a neuropsychological study of patients with psychotic epilepsy and education level–matched controls.
Results: Among 336 new referrals of epilepsy, a higher prevalence of psychotic disorders was found among patients with ID (24%) than among those with normal intelligence (6%). The psychotic symptoms and operational diagnoses of psychotic epilepsy patients with ID were similar to those of patients with normal intelligence. A wide range (7–86%) of psychotic epilepsy patients was diagnosed as having schizophrenia, depending on the operational criteria used. Patients with psychotic epilepsy had more disturbances in verbal memory and attention functions than did the controls.
Conclusions: Epilepsy patients with ID show a predisposition to develop psychotic disorders. Distinguishing their psychotic symptoms from those of schizophrenia is difficult. Subtle cognitive disturbances predispose to psychotic disorders in epilepsy.     

Familial association of neuropsychological traits in patients with generalized and partial seizure disorders

To investigate familial effects of neuropsychological deficits associated with seizure disorders, we studied 65 families, in which 1 member had epilepsy. The disorders included childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME) and temporal lobe epilepsy (TLE). Age-appropriate tests were administered to assess sustained attention, encoding and verbal memory, executive and focused attention and attentional flexibility/impulsivity. CAE probands attained lower scores than other probands in visual sustained attention and the ability to focus on and execute a visual-motor task. Scores of the unaffected relatives tended to fall between those of the probands and the controls. JME relatives had lower scores than other relatives in tests of visual and auditory sustained attention and attentional flexibility, and showed greater variability in response time. Behavioral information of this type may aid in the specification and differentiation of genetic linkages in affected families.     

Attention and memory evaluation across the life span: heterogeneous effects of age and education

The developmental sequences of attention and memory were studied by utilizing normative data derived from the neuropsychological battery named NEUROPSI ATTENTION AND MEMORY. A sample of 521 Spanish-speaking individuals, aged 6 to 85 years, participated in this study. In the adult sample, educational level ranged from 0 to 22 years of education. Data from subtests measuring orientation, attention and concentration, executive functions, working memory, immediate and delayed verbal memory, and immediate and delayed visual memory were included. The factor structure of the analyzed battery is presented. The effects of age and education on this structure were analyzed. Results suggested that although attention and memory are related, their developmental sequences are separated from one another. During childhood, the development of selective and sustained attention, attentional-working memory, and executive functions showed a fast improvement in performance. Development of verbal memory and place and person orientation showed a slower increment in scores. In the adult sample it was found that factors related to memory are sensitive to age, whereas those related to attention and executive functions are sensitive to education. The consideration of both the developmental sequence, as well as differential effects of education, can improve the sensitivity and specificity of neuropsychological measures, allowing early diagnosis of cognitive dysfunction and implementation of adequate rehabilitation programs.     

Neurocognitive development of children with congenital unilateral brain lesion and epilepsy

The aim of this study was to specify the neuropsychological deficits characteristic of children with unilateral non-progressive brain lesion. In order to assess these specific functions, we used a comprehensive model of congenital hemiparesis with partial epilepsy and newly diagnosed partial epilepsy without hemiparesis. The neuropsychological examination was performed using the NEPSY test battery on 44 children aged from 4 to 9 years. The children were divided into three groups: 18 children suffering from congenital hemiparesis with chronic partial epilepsy, 12 children with newly diagnosed partial epilepsy prior to anti-epileptic treatment, and 14 healthy controls matched by sex, age, and socioeconomic status. Children with congenital hemiparesis and epilepsy had a more clearly expressed cognitive dysfunction, especially in language, visuo-perceptual and memory tasks, than children with newly diagnosed partial epilepsy. The profile of cognitive weakness appears to be diffuse and quite similar in both groups, and it did not demonstrate a clear effect of lateralization, according to the side of epileptic electroencephalogram discharges. Children within both groups are likely to have a high risk of developing attention, phonological, visuo-perceptual, and memory deficits in their life. Especially interesting and surprising was the fact that the newly diagnosed epilepsy group demonstrated impairment not only in attention, visuo-perceptual and short-term memory skills, but also in auditory perception, lexical function, and the comprehension of speech. Therefore, it is recommended that children with epilepsy would undergo neuropsychological examination in order to assess their cognitive abilities.     

Evaluation of cognition, structural, and functional MRI in juvenile myoclonic epilepsy

Purpose:  Previous studies using advanced imaging techniques have suggested subtle structural and functional changes in patients with juvenile myoclonic epilepsy (JME), mainly associated with the frontal lobes. In addition, it has been reported that these patients show neuropsychological deficits, often summarized as frontal lobe dysfunction. The aim of this study was a comprehensive analysis of neuropsychological parameters, and functional and structural magnetic resonance imaging (MRI) in an independent cohort of patients with JME.
Methods:  We studied 19 JME patients and 20 age-, sex-, and education-matched controls using a battery of standardized neuropsychological tests, optimized voxel-based morphometry (VBM), and two domain-specific working-memory paradigms combined with functional MRI (fMRI).
Results:  Our investigations did not reveal statistically significant differences between the groups of JME patients and normal controls in either the VBM or the fMRI study of working memory. The neuropsychological examination showed a slightly worse performance for the JME patients across most tests used, reaching statistical significance for semantic and verbal fluency.
Conclusions:  In our cohort of JME patients, we could not reproduce the findings of frontal gray matter changes from previous studies, and we could not detect an fMRI correlate of previously reported differences in working memory in JME. The neuropsychological deficits may be attributed partially to antiepileptic medication. We conclude that structural and functional frontal lobe deficits in JME patients have to be interpreted with care. One reason for a variation between different cohorts may be the genetic heterogeneity of the disease.