Features of the broader autism phenotype in people with epilepsy support shared mechanisms between epilepsy and autism spectrum disorder

Richard, A.E., I.E. Scheffer and S.J. Wilson. Features of the broader autism phenotype in people with epilepsy support shared mechanisms between epilepsy and autism spectrum disorder. NEUROSCI BIOBEHAV REV 21(1) XXX–XXX, 2016. To inform on mechanisms underlying the comorbidity of epilepsy and autism spectrum disorder (ASD), we conducted meta-analyses to test whether impaired facial emotion recognition (FER) and theory of mind (ToM), key phenotypic traits of ASD, are more common in people with epilepsy (PWE) than controls. We contrasted these findings with those of relatives of individuals with ASD (ASD-relatives) compared to controls. Furthermore, we examined the relationship of demographic (age, IQ, sex) and epilepsy-related factors (epilepsy onset age, duration, seizure laterality and origin) to FER and ToM. Thirty-one eligible studies of PWE (including 1449 individuals: 77% with temporal lobe epilepsy), and 22 of ASD-relatives (N = 1295) were identified by a systematic database search. Analyses revealed reduced FER and ToM in PWE compared to controls (p < 0.001), but only reduced ToM in ASD-relatives (p < 0.001). ToM was poorer in PWE than ASD-relatives. Only weak associations were found between FER and ToM and epilepsy-related factors. These findings suggest shared mechanisms between epilepsy and ASD, independent of intellectual disability.     

Understanding relationships between autism,intelligence, and epilepsy: a cross‐disorder approach

Aim As relationships between autistic traits, epilepsy, and cognitive functioning remain poorly understood, these associations were explored in the biologically related disorders tuberous sclerosis complex (TSC), neurofibromatosis type 1 (NF1), and epilepsy. Method The Social Responsiveness Scale (SRS), a quantitative measure of autistic traits, was distributed to caregivers or companions of patients with TSC, NF1, and childhood‐onset epilepsy of unknown cause (EUC), and these results were compared with SRS data from individuals with idiopathic autism spectrum disorders (ASDs) and their unaffected siblings. Scores and trait profiles of autistic features were compared with cognitive outcomes, epilepsy variables, and genotype. Results A total of 180 SRS questionnaires were completed in the TSC, NF1, and EUC outpatient clinics at the Massachusetts General Hospital (90 females, 90 males; mean age 21y, range 4–63y), and SRS data from 210 patients with ASD recruited from an autism research collaboration (167 males, 43 females; mean age 9y, range 4–22y) and 130 unaffected siblings were available. Regression models showed a significant association between SRS scores and intelligence outcomes (p<0.001) and various seizure variables (p<0.02), but not with a specific underlying disorder or genotype. The level of autistic features was strongly associated with intelligence outcomes in patients with TSC and epilepsy (p<0.01); in patients with NF1 these relationships were weaker (p=0.25). For all study groups, autistic trait subdomains covaried with neurocognitive comorbidity, with endophenotypes similar to that of idiopathic autism. Interpretation Our data show that in TSC and childhood‐onset epilepsy, the severity and phenotype of autistic features are inextricably linked with intelligence and epilepsy outcomes. Such relationships were weaker for individuals with NF1. Findings suggest that ASDs are not specific in these conditions.     

Medically refractory epilepsy in autism

Purpose: Epilepsy and electroencephalographic abnormalities are frequent in idiopathic autism, but there is little information regarding treatment‐resistant epilepsy (TRE) in this group. We sought to define the clinical and electrophysiologic characteristics and treatment outcomes in these patients. Methods: We retrospectively reviewed clinical and laboratory data of patients with idiopathic autism evaluated at NYU Epilepsy Center during a 20‐year period. Key Findings: One hundred twenty‐seven patients had idiopathic autism and at least one epileptic seizure; 33.9% had TRE and 27.5% were seizure free. The remaining 38.6% of patients had infrequent seizures or insufficient data to categorize. Patients with TRE had a significantly earlier onset of seizures than seizure‐free patients, and a trend for more developmental regression and motor and language delays. Three patients had surgical resection (two had limited improvement and one had no improvement) and one had an anterior callosotomy (no improvement). Vagus nerve stimulator (VNS) implantation provided limited improvement (2 patients) and no improvement (7). Significance: This study found that TRE is common in idiopathic autism and more common with early age of seizure onset. Relatively few patients underwent surgical resection due to multifocal partial epilepsy, comorbid generalized epilepsy, or limited impact of ongoing partial seizures given other problems related to autism. Our small sample suggests that surgical and VNS outcomes in this group are less favorable than in other TRE populations.     

Study of the relationships between self-injurious behavior and pain reactivity in infantile autism]

Autism can be considered as an early general developmental disorder, characterized by problems of social interaction, problems of verbal and non verbal communication, and behavioral or ideational stereotypes. However, within autism we observe a clinical heterogeneity of autistic disorders which suggests the possibility of autistic subtypes. Several authors hypothesize an analgesia among autistic children; this analgesia may be related to self-mutilation found among autistics. The current research had two objectives: 1) to develop and validate evaluation tools for measuring aggression directed towards the self (Yale-Paris Self-Injurious Behavior Scale: YAPA SIB) and pain reactivity (Pre-Linguistic Behavioral Pain Reactivity Scale: PLBPRS); instruments appropriate for autistics and capable of showing different behavioral sub-types; 2) to study in 80 autistic children pain reactivity, self-injurious behavior, and their relation in different observational situations. The results show that the scales of self-injurious behavior and pain reactivity have good discriminative capacity, good test-retest reliability, and good validity. The results suggest additionally that the apparent decreased pain reactivity observed in autistics does not derive from a real analgesia but from a different mode of pain expression related to difficulties with verbal communication, body representation and certain cognitive disorders (learning disorders, problems representing sensations and emotions, problems establishing cause-effect relationships). Additionally, there is a significant relationship between certain self-injurious behaviors and the apparent reduced pain reactivity. Interpretations of this result are presented and the possible role of stress in autism is discussed.     

Perceived epilepsy stigma mediates relationships between personality and social well-being in a diverse epilepsy population

IntroductionPerceived epilepsy stigma and reduced social well-being are prevalent sources of distress in people with epilepsy (PWE). Yet, research on patient-level correlates of these difficulties is lacking, especially among underserved groups.Materials and methodsRacially/ethnically diverse adults with intractable seizures (N = 60, 62% female; 79% Black, 20% Hispanic/Latino, 8% White) completed validated measures of personality (NEO Five Factor Inventory, NEO-FFI-3), perceived epilepsy stigma (Epilepsy Stigma Scale, ESS), and quality of life (Quality of Life Inventory in Epilepsy, QOLIE-89). Controlling for covariates, ordinary least-squares (OLS) regression evaluated the total, direct, and indirect effects of NEO-FFI-3 neuroticism and extraversion scores on epilepsy-related social well-being (i.e., combination of QOLIE-89 social isolation and work/driving/social function subscales, α = 0.87), mediated through perceived stigma.ResultsIn separate models, higher levels of neuroticism (N) and lower levels of extraversion (E) were significantly and independently associated with greater perceived stigma (N path a = 0.71, p = 0.005; E path a = − 1.10, p < 0.005). Stigma, in turn, was significantly and independently associated with poorer social well-being (N path b = 0.23, p < 0.001; E path b = − 0.23, p < 0.001). Bias-corrected bootstrap confidence intervals (CIs) showed that neuroticism and extraversion were indirectly associated with social well-being through their respective associations with perceived stigma (N path ab = − 0.16, 95% CIs [− 0.347, − 0.044]; E path ab = 0.25, 95% CIs [0.076, 0.493]).ConclusionHigher neuroticism and lower extraversion covaried with stigma beliefs, and these may be markers of poor social outcomes in PWE. Mediation models suggest that targeting epilepsy stigma beliefs may be a particularly useful component to incorporate when developing interventions aimed at promoting social well-being in diverse PWE.     

Current concepts and controversies in prion immunopathology

Scrapie in sheep and new variant Creutzfeldt-Jakob disease in humans are typically initiated by extracerebral exposure to prions. Both exhibit early prion accumulation in sites of the peripheral lymphoreticular system, such as splenic or lymph nodal germinal centers. In germinal centers, follicular dendritic cells (FDCs), whose development and maintenance depend on lymphotoxin and tumor necrosis factor signaling, are believed to be the main cell type for efficient prion replication in the periphery. Here, we discuss the molecular requirements for prion replication competence in stromal and lymphoid compartments of lymphoid organs. In addition, we examine the preconditions of transepithelial passage of prions in the mucosal-associated lymphoid system. Our results suggest that under specific conditions, efficient prion replication in mesenteric and inguinal lymph nodes is possible in the absence of mature FDCs. M cells are a plausible candidate for the mucosal portal of prion infection.     

Pervasive developmental disorders: controversies concerning the classification of autism

Autistic Disorder was described by Leo Kanner in 1943. Since that time not only the name of this disorder (initially early infantile autism) has changed but also it's relation to other disorders. DSM-IV includes autism together with Rett's Disorder, Childhood Disintegrative Disorder, Asperger's Disorder and Pervasive Developmental Disorder Not Otherwise Specified into one category: Pervasive Developmental Disorders. The definition and contents of Pervasive Developmental Disorders raise many controversies. Differentiation between particular disorders within this category is also difficult. This paper discusses some of these problems.     

儿童孤独症出生季节与不良因素的关系分析

目的　了解儿童孤独症出生高的季节与相关因素的关系。方法　 1986～ 1996年间对南京儿童心理卫生研究中心的儿童孤独症患儿 ( 12 4例 )与年龄、性别相近的正常儿童 ( 12 0例 )进行对照分析。结果　孤独症患儿的出生季节以春季 ( 3～ 5月 )和秋季 ( 9～ 11月 )为高。妊娠期和围产期有不良因素者明显高于对照组。结论　在春季出生的婴儿尤其要避免妊娠早期和围产期不良因素的影响     

The treatment of epilepsy in autism

Autism is associated with epilepsy. One third of the population of people with autism have developed seizures in early adult life. In spite of this well-known association, little is known about the treatment of epilepsy in autism. This paper reviews the sparse literature and reports a systematic case-record study of the treatment of epilepsy in autism. Some practical guidelines for clinicians are provided. Research in the field of epilepsy in autism is highly warranted.This study has been supported by a grant from The Commission for Social Research, Sweden, No. E 88/170:2.     

Sleep,epilepsy, and autism

The purpose of this review article is to explore the links between sleep and epilepsy and the treatment of sleep problems in children with autism spectrum disorder (ASD). Epilepsy and sleep have bidirectional relationships, and problems with both are highly prevalent in children with ASD. Literature is reviewed to support the view that sleep is particularly important to address in the context of ASD. Identification and management of sleep disorders may improve seizure control and challenging behaviors. In closing, special considerations for evaluating and treating sleep disorders in children with ASD and epilepsy are reviewed.This article is part of a Special Issue entitled “Autism and Epilepsy”.     

孤独症伴发癫痫的相关性研究

目的探讨癫痫与孤独症间的相关性,分析两者间的关系。方法选取2011-04—2014-04在海淀区培智学校就读的146例孤独症患者为研究对象,根据是否发生癫痫,将其分为观察组和对照组,对照组21例,观察组125例,对比2组的临床表现和体征等资料,分析癫痫并孤独症患者的主要临床表现,及其与癫痫发作可能相关的独立因素。结果结果显示观察组发生孤独症的临床表现以社会交往障碍和交流障碍为主,分别占42.86%、23.81%;单因素分析结果显示在合并其他神经系统疾病、脑电图异常情况、母亲孕期异常及癫痫家族病史等方面,2组比较差异有统计学意义(P均0.05);Logistic回归分析显示合并其他神经系统疾病、脑电图异常、母亲孕期异常是孤独症患者发生癫痫的独立危险因素(P均0.05)。结论癫痫与孤独症间存在相关性,应针对其独立相关因素对患孤独症的青少年进行干预,从而预防癫痫的发生。     

成年癫痫患者的自杀风险及相关危险因素研究

目的：研究成人癫痫患者自杀风险及相关危险因素。方法采用简明国际神经精神访谈（MINI）自杀风险模块和抑郁障碍模块对211例我院门诊的成年癫痫患者进行心理评估,并详细记录患者的年龄、性别、就业状况、婚姻、教育年限、发病年龄、病程、发作类型、发作频率、头颅M RI结果以及使用抗癫痫药种数,比较上述因素与自杀风险的关系。结果本组病例中有自杀风险的患者占21.3％（45/211）,伴抑郁障碍的患者占17.1％（36/211）;而伴抑郁障碍患者的自杀风险高达75.0％（27/36）,非抑郁障碍患者的自杀风险达10.3％（18/175）,差异有统计学意义（χ2＝74.525,P＜0.01）。结论伴抑郁障碍的癫痫患者自杀风险更高。     

Cholesterol and statins in Alzheimer's disease: Current controversies

Alzheimer's disease (AD) is the principal cause of dementia in older people, and accumulation of amyloid-beta (Aβ) peptide is a crucial event in AD pathogenesis. Despite opposite results found in literature, increased evidence posits that high cholesterol levels enhance the risk to develop AD. In fact, cholesterol metabolism and catabolism are affected in this neurodegenerative disorder. Since amyloid precursor protein (APP) processing and subsequent Aβ production are dependent on membrane cholesterol content and on levels of isoprenoid intermediates in the cholesterol biosynthesis pathway, changes in cholesterol might have different consequences on Aβ formation. These pieces of evidence support that inhibitors of cholesterol synthesis, like statins, could have a therapeutic role in AD. Many studies about the effect of statins use in AD show conflicting results; however, some authors explain it by the differences in administrated doses. Recent studies demonstrate that statins can efficiently decrease Aβ formation from APP and be neuroprotective against the peptide toxicity. Because of the high number of pleiotropic effects of statins, novel molecular mechanisms that account for the beneficial effect of these drugs on AD might be discovered in a near future.     

Siblings relationships of children with autism

This study investigated sibling relationships of children with autism compared to children with Down syndrome and siblings of normally developing children. Ninety siblings (30 per group) between the ages of 8 and 18 participated in this study. Results indicated that sibling relationships in families of children with autism were characterized by less intimacy, prosocial behavior, and nurturance than those of the two comparison groups. Both siblings of children with autism and siblings of children with Down syndrome reported greater admiration of their sibling and less quarreling and competition in their relationships relative to normally developing comparison children.     

Neuropeptide Y and epilepsy: recent progress, prospects and controversies

Neuropeptide Y (NPY), a 36 amino-acid member of the pancreatic polypeptide family, has received considerable attention in recent years as an endogenous modulator of epileptic activity. Prominently expressed in brain regions involved in seizure generation and propagation, NPY can exert powerful effects on synaptic transmission. Here, we discuss the anti-epileptic actions of NPY and receptor subtypes responsible.     

Current controversies in pathophysiology of cervical spondylotic myelopathy

Cervical spondylotic myelopathy is the most severe consequence of degenerative disease of cervical spine. In this article we perform a bibliographic review, addressing current controversies in its pathophysiology. Present work lines of most groups dedicated to the study of this condition are focused on improving surgical techniques designed for the treatment of this disease. Pathophysiological studies are scarce, and most of our pathophysiological knowledge of cervical spondylotic myelopathy is based in works done in 60s and 70s. Literature of the last decade lacks neurochemichal studies parallel to those existing for acute spinal injury. In the same way, only three prospective clinical trials comparing conservative and surgical treatment have been done, and none of them has demonstrated clear superiority of surgery. Given the high prevalence of this disease, the need for deep knowledge of its pathophysiologic, neurochemichal and molecular basis, and the optimization of surgical treatment is justified. This probably implies the need for prospective randomized trials to determine which patients are going to benefit from surgery.     

Routine developmental and autism screening in an epilepsy care setting

Developmental delay (delay) and co-morbidities like autism are common in children with epilepsy. We assessed the yield of routine screening for delay and autism in a hospital-based program. Parents completed developmental and autism screeners for 65 children (average age=2.5y; 38(58%) boys). Forty-nine (75%) were established epilepsy patients, and 16 (25%) were new patients. For development, 47 (72%) children screened positive and 8 (12%) had borderline results. Twenty-four (37%) scored positive for autism, all of whom also screened positive for developmental delay. Delays and neurologic deficits accounted for the positive autism results in 20 of the 24. Developmental findings were confirmatory (already receiving services) in 32/55 (58%) children and actionable in 17 (31%) (requiring further evaluation). Referrals for further evaluations were made for most with actionable findings. The yield of routine screening of children in a tertiary center is sufficiently high to support its use and to consider screening of all children seen with epilepsy.