Search tips
Search criteria

Results 1-25 (37)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
1.  Epilepsy and Parent Stress: The Chicken and the Egg Dilemma 
Epilepsy Currents  2015;15(1):13-14.
PMCID: PMC4320948
2.  Neurobehavioral comorbidities of pediatric epilepsies are linked to thalamic structural abnormalities 
Epilepsia  2013;54(12):2116-2124.
Neurobehavioral comorbidities are common in pediatric epilepsy with enduring adverse effects on functioning, but their neuroanatomical underpinning is unclear. Striatal and thalamic abnormalities have been associated with childhood-onset epilepsies, suggesting that epilepsy-related changes in the subcortical circuit might be associated with the combordities of children with epilepsy. We aimed to compare subcortical volumes and their relationship with age in children with complex partial seizures (CPS), childhood absence epilepsy (CAE), and healthy controls (HC). We examined the shared versus unique structural-functional relationships of these volumes with behavior problems, intelligence, language, peer interaction, and epilepsy variables in these two epilepsy syndromes.
We investigated volumetric differences of caudate, putamen, pallidum, and thalamus in children with CPS (N= 21), CAE (N=20), and HC (N=27). Study subjects underwent structural MRI, intelligence, and language testing. Parent-completed Child Behavior Checklists provided behavior problem and peer interaction scores. We examined the association of age, IQ, language, behavioral problems, and epilepsy variables with subcortical volumes that were significantly different between the children with epilepsy and HC.
Both children with CPS and CAE exhibited significantly smaller left thalamic volume compared to HC. In terms of developmental trajectory, greater thalamic volume was significantly correlated with increasing age in children with CPS and CAE but not in HC. With regard to the comorbidities, reduced left thalamic volumes were related to more social problems in children with CPS and CAE. Smaller left thalamic volumes in children with CPS were also associated with poor attention, lower IQ and language scores, and impaired peer interaction.
Our study is the first to directly compare and detect shared thalamic structural abnormalities in children with CPS and CAE. These findings highlight the vulnerability of the thalamus and provide important new insights on its possible role in the neurobehavioral comorbidities of childhood-onset epilepsy.
PMCID: PMC4259153  PMID: 24304435
3.  Screening for Suicidal Ideation in Children with Epilepsy 
Epilepsy & behavior : E&B  2013;29(3):521-526.
Given the FDA’s warning regarding the potential connection between suicidal behavior and antiepileptic drugs, this study examined methods by which to detect suicidal ideation in children with epilepsy. It compared the sensitivity, specificity, and area under the curve for identifying children with suicidal behavior using the Child Behavior Checklist (CBCL) and a structured psychiatric interview. Parent completed CBCLs provided behavior problem scores on 177 children with epilepsy, aged 5–16 years. Psychiatric diagnoses were made based on separate child and parent structured psychiatric interviews about the child. Children answered questions on suicidal behaviors during the interview. The clinically elevated CBCL Total Problems scale and having more than one psychiatric diagnosis, irrespective of type of diagnosis, were significant predictors and correctly classified children with suicidal ideation in 79% of the cases based on the CBCL and 80% of the cases with more than one psychiatric diagnosis. These findings indicate that elevated CBCL Total Problems scores, a commonly used instrument, can screen and identify risk for suicidal behavior in children with epilepsy. Additionally, irrespective of diagnosis, if a child with epilepsy has more than one psychiatric diagnosis, further assessment of suicidal behavior is warranted. Importantly, the results underscore the utility of having parents complete a questionnaire in the waiting room in order to identify children with epilepsy at risk for suicidal behavior.
PMCID: PMC4079123  PMID: 24128934
pediatric epilepsy; suicide; psychiatric disorders; behavior problems
4.  Brain Growth Rate Abnormalities Visualized in Adolescents with Autism 
Human brain mapping  2011;34(2):425-436.
Autism spectrum disorder (ASD) is a heterogeneous disorder of brain development with wide-ranging cognitive deficits. Typically diagnosed before age 3, ASD is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared to those of typically developing children and adolescents. Using tensor-based morphometry (TBM), we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and 7 typically developing boys (mean age/inter-scan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole-brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (p = 0.03, corrected), especially in the parietal (p = 0.008), temporal (p = 0.03) and occipital lobes (p =0.02). We also visualized abnormal overgrowth in autism in some gray matter structures, such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. TBM revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects.
PMCID: PMC4144412  PMID: 22021093
Autism spectrum disorder; longitudinal; MRI; tensor-based morphometry; development; white matter
5.  Adaptive behavior and later school achievement in children with early-onset epilepsy 
To determine whether early measures of adaptive behavior are predictive of later school difficulties and achievement in otherwise neurotypical (unimpaired) children with onset of epilepsy during the pre-school years.
In a prospective cohort study, parents completed the Vineland Adaptive Behavior Scales (VABS) for children who were aged 5 years or less at epilepsy diagnosis. Eight to nine years later, the children were assessed using the Wechsler Intelligence Scales for Children (WISC), the Wide Range Achievement Test (WRAT), and the Child Behavior Checklist (CBCL). Associations of VABS scores with later WRAT and CBCL scores were tested.
A total of 108 neurotypical children (64 males, 44 females; mean age at testing 11y 11mo, SD 2y) were studied. After adjustment for IQ and other factors, there was an increase of 0.15 points (95% confidence interval [CI] 0.03–0.27 points; p=0.03) and 0.14 points (95% CI 0.0–0.28 points; p=0.05) in WRAT reading and spelling scores for each 1-point increment in the VABS communication score. Corresponding numbers for the VABS socialization score were 0.20 (95% CI 0.08–0.32; p=0. 005) and 0.17 (95% CI 0.05–0.29; p=0.005).
In neurotypical preschool children with epilepsy, early social and communication scores predict later school performance. These findings raise questions about opportunities for early identification and intervention for children at greatest risk.
PMCID: PMC3676436  PMID: 23534842
6.  How to Advance the Debate on Nonspecific vs Specific Seizure Type and Comorbidity Profile 
Epilepsy Currents  2014;14(4):191-193.
PMCID: PMC4120386  PMID: 25170314
7.  Antiepileptic Drugs and Suicide: The Light at the End of the Tunnel 
Epilepsy Currents  2014;14(3):125-126.
PMCID: PMC4038273  PMID: 24940152
8.  Why Hemispheric Lateralization of Language is Only Part of the Story in Epilepsy Surgery Candidates 
Epilepsy Currents  2014;14(3):134-135.
PMCID: PMC4038277  PMID: 24940156
9.  Childhood Absence Epilepsy: What Is All the Distraction About? 
Epilepsy Currents  2014;14(2):71-72.
PMCID: PMC4010879  PMID: 24872781
10.  Imaging and Genetics of Language and Cognition in Pediatric Epilepsy 
Epilepsy & behavior : E&B  2012;26(3):303-312.
This paper presents translational aspects of imaging and genetic studies of language and cognition in children with epilepsy of average intelligence. It also discusses current unanswered translational questions in each of these research areas. A brief review of multimodal imaging and language study findings shows that abnormal structure and function, as well as plasticity and reorganization in language-related cortical regions are found both in children with epilepsy with normal language skills and in those with linguistic deficits. The review on cognition highlights that multiple domains of impaired cognition and abnormalities in brain structure and/or connectivity are evident early on in childhood epilepsy and might be specific for epilepsy syndrome. The description of state of the art genetic analyses that can be used to explain the convergence of language impairment and Rolandic epilepsy includes a discussion of the methodological difficulties involved in these analyses. Two junior researchers describe how their current and planned studies address some of the unanswered translational questions regarding cognition and imaging and the genetic analysis of speech sound disorder, reading, and centrotemporal spikes in Rolandic epilepsy.
PMCID: PMC3732317  PMID: 23116771
language; cognition; imaging; genetics; pediatric epilepsy
11.  White matter integrity, language, and childhood onset schizophrenia 
Schizophrenia Research  2012;138(2-3):150-156.
The heterogeneity of symptoms and cognitive deficits in schizophrenia can be explained by abnormal connectivity between brain regions. Childhood-onset schizophrenia (COS) is a particularly severe form of schizophrenia, with an onset during a key time period for both cerebral pruning and myelination.
Diffusion tensor images were acquired from 18 children and adolescents with COS and 25 controls. The COS group was divided into two sub-groups--one with linguistic impairment (LI) and the other without (NLI). The fractional anisotropy (FA), axial (AD), and radial diffusivity (RD) data from the two COS sub-groups were compared to each other and to the controls using tract-based spatial statistics (TBSS) analyses, which is a voxel-based method used to identify regions of white matter abnormalities.
TBSS identified several regions in the left hemisphere where the LI group had increased AD and RD relative to the NLI and the control groups. These areas primarily localized to linguistic tracts: left superior longitudinal fasciculus and left inferior longitudinal fasciculus/inferior fronto-occipital fasciculus. Regions of increased RD overlapped regions of increased AD, with the former showing more pronounced effects.
Studies of adult-onset schizophrenia typically identify areas of higher RD but unchanged AD; however, normal development studies have shown that while RD decreases are pronounced over this age range, smaller decreases in AD can also be detected. The observed increases in both RD and AD suggest that developmental disturbances affecting the structural connectivity of these pathways are more severe in COS accompanied by severe linguistic impairments.
PMCID: PMC3372669  PMID: 22405729
Diffusion tensor imaging; Axial diffusivity; Radial diffusivity; Linguistic impairments; Neurodevelopment
12.  Stress and Seizure Control in Children: Where to Now? 
Epilepsy Currents  2013;13(4):158-159.
PMCID: PMC3763596  PMID: 24009475
13.  Psychopathology and Seizure Threshold 
Epilepsy Currents  2013;13(3):141-142.
PMCID: PMC3697884  PMID: 23840176
14.  Familial clustering of epilepsy and behavioral disorders: Evidence for a shared genetic basis 
Epilepsia  2011;53(2):301-307.
To examine whether family history of unprovoked seizures is associated with behavioral disorders in epilepsy probands, thereby supporting the hypothesis of shared underlying genetic susceptibility to these disorders.
We conducted an analysis of the 308 probands with childhood onset epilepsy from the Connecticut Study of Epilepsy with information on first degree family history of unprovoked seizures and of febrile seizures whose parents completed the Child Behavior Checklist (CBCL) at the 9-year follow-up. Clinical cut-offs for CBCL problem and DSM-Oriented scales were examined. The association between first degree family history of unprovoked seizure and behavioral disorders was assessed separately in uncomplicated and complicated epilepsy and separately for first degree family history of febrile seizures. A subanalysis, accounting for the tendency for behavioral disorders to run in families, adjusted for siblings with the same disorder as the proband. Prevalence ratios were used to describe the associations.
Key findings
In probands with uncomplicated epilepsy, first degree family history of unprovoked seizure was significantly associated with clinical cut-offs for Total Problems and Internalizing Disorders. Among Internalizing Disorders, clinical cut-offs for Withdrawn/Depressed, and DSM-Oriented scales for Affective Disorder and Anxiety Disorder were significantly associated with family history of unprovoked seizures. Clinical cut-offs for Aggressive Behavior and Delinquent Behavior, and DSM-Oriented scales for Conduct Disorder and Oppositional Defiant Disorder were significantly associated with family history of unprovoked seizure. Adjustment for siblings with the same disorder revealed significant associations for the relationship between first degree family history of unprovoked seizure and Total Problems and Agressive Behavior in probands with uncomplicated epilepsy; marginally significant results were seen for Internalizing Disorder, Withdrawn/Depressed and Anxiety Disorder.
There was no association between family history of unprovoked seizure and behavioral problems in probands with complicated epilepsy. First degree family history of febrile seizure was not associated with behavioral problems in probands with uncomplicated or in those with complicated epilepsy.
Increased occurrence of behavioral disorders in probands with uncomplicated epilepsy and first degree family history of unprovoked seizure suggests familial clustering of these disorders. This supports the idea that behavioral disorders may be another manifestation of the underlying pathophysiology involved in epilepsy or closely related to it.
PMCID: PMC3267857  PMID: 22191626
epilepsy; psychiatric disorders; family history; epidemiology
15.  Psychopathology in Pediatric Epilepsy: Role of Antiepileptic Drugs 
Children with epilepsy are usually treated with antiepileptic drugs (AEDS). Some AEDs adversely affect behavior in susceptible children. Since psychiatric comorbidity is prevalent in pediatric epilepsy, this paper attempts to disentangle these AED side effects from the psychopathology associated with this illness. It first outlines the clinical and methodological problems involved in determining if AEDs contribute to the behavior and emotional problems of children with epilepsy. It then presents research evidence for and against the role AEDs play in the psychopathology of children with epilepsy, and outlines how future studies might investigate this problem. A brief description of how to clinically separate out AED effects from the complex illness-related and psychosocial factors that contribute to the behavior difficulties of children with epilepsy concludes the paper.
PMCID: PMC3516700  PMID: 23233847
antiepileptic drugs; epilepsy; psychopathology; children
16.  Proton Magnetic Resonance Spectroscopy and Thought Disorder in Childhood Schizophrenia 
Schizophrenia research  2011;133(1-3):82-90.
Although magnetic resonance spectroscopy has identified metabolic abnormalities in adult and childhood schizophrenia, no prior studies have investigated the relationship between neurometabolites and thought disorder. This study examined this association in language-related brain regions using proton magnetic resonance spectroscopic imaging (1H MRSI).
MRSI was acquired bilaterally from 28 youth with childhood-onset schizophrenia and 34 healthy control subjects in inferior frontal, middle frontal, and superior temporal gyri at 1.5 T and short echo time (TR/TE=1500/30 ms). CSF-corrected “total NAA” (tNAA; N-acetyl-aspartate+N-acetyl-aspartyl-glutamate), glutamate+glutamine (Glx), creatine+phosphocreatine (Cr+PCr), choline compounds (Cho), and myo-inositol (mI) were assayed in manually drawn regions-of-interest partitioned into gray matter, white matter, and CSF and then coregistered with MRSI. Speech samples of all subjects were coded for thought disorder.
In the schizophrenia group, the severity of formal thought disorder correlated significantly with tNAA in the left inferior frontal and superior temporal gyri and with Cr+PCr in left superior temporal gyrus.
Neurometabolite concentrations in language-related brain regions are associated with thought disorder in childhood-onset schizophrenia.
PMCID: PMC3229835  PMID: 21872444
Childhood-onset schizophrenia; Thought Disorder; Magnetic Resonance Spectroscopy; N-acetyl aspartate; Choline compounds
17.  Psychiatric and Medical Comorbidity and Quality of Life Outcomes in Childhood-Onset Epilepsy 
Pediatrics  2011;128(6):e1532-e1543.
We compared associations of epilepsy remission status and severity as well as psychiatric and other comorbidities with child and parent-proxy reports of health-related quality of life (HRQoL) in adolescents previously diagnosed with epilepsy.
In a prospective, community-based study of newly diagnosed childhood epilepsy, HRQoL of 277 children was assessed 8 to 9 years after diagnosis by using child and parent-proxy versions of the Child Health Questionnaire (CHQ). Multiple linear regression models adjusted for age and gender were used to compare associations of epilepsy remission and “complicated” epilepsy (secondary to an underlying neurologic insult or epileptic encephalopathy) status and psychiatric and other comorbidities with HRQoL.
Mean age of epilepsy onset was 4.4 years (SD: 2.6). At the 9-year reassessment, children were, on average, 13.0 years old (SD: 2.6); 64% were seizure-free for 5 years, 31% were taking antiepileptic drugs, and 19% had a complicated epilepsy. Prevalence of comorbidities at follow-up were 26% psychiatric diagnosis; 39% neurodevelopmental spectrum disorder (NDSD); 24% chronic medical illness; and 15% migraine. In multivariable analysis, having a psychiatric disorder was broadly associated with child (6 of 11 scales) and parent-proxy (7 of 12 scales) HRQoL (P ≤ .0125). Five-year remission and complicated epilepsy status had few or no associations with HRQoL. Although parent-proxy HRQoL was strongly associated with NDSD (6 of 11 scales), child-reported HRQoL was not (2 of 11 scales).
Psychiatric comorbidities are strongly associated with long-term HRQoL in childhood-onset epilepsy, which suggests that comprehensive epilepsy care must include screening and treatment for these conditions, even if seizures remit.
PMCID: PMC3387901  PMID: 22123895
epilepsy; psychiatric comorbidity; quality of life; Child Health Questionnaire; child and adolescent health
18.  Baseline Psychiatric Evaluations Are Needed to Treat Seizures 
Epilepsy Currents  2012;12(6):236-237.
PMCID: PMC3577131  PMID: 23447722
19.  Psychopathology and Epilepsy: A Two-Way Relationship 
Epilepsy Currents  2012;12(5):201-202.
PMCID: PMC3482720  PMID: 23118609
20.  Diminished grey matter within the hypothalamus in autism disorder: a potential link to hormonal effects? 
Biological psychiatry  2011;70(3):278-282.
Subjects with autism suffer from impairments of social interaction, deviations in language usage, as well as restricted and stereotyped patterns of behavior. These characteristics are found irrespective of age, IQ and gender of affected subjects. However, brain changes due to age, IQ and gender may pose potential confounds in autism neuroimaging analyses.
To investigate grey matter differences in autism that are not related to these potential confounds, we performed a VBM analysis in 52 affected children and adolescents and 52 matched control subjects.
We observed diminished grey matter in a region of the hypothalamus, which synthesizes the behaviorally relevant hormones oxytocin and arginine vasopressin.
This finding provides support for further investigations of the theory of abnormal functioning of this hormonal system in autism and potentially for experimental therapeutic approaches using oxytocin and related neuropeptides.
PMCID: PMC3134572  PMID: 21531390
ASD; VBM; children; adolescents; oxytocin; morphometry
21.  Intelligence and Cortical Thickness in Children with Complex Partial Seizures 
NeuroImage  2011;57(2):337-345.
Prior studies on healthy children have demonstrated regional variations and a complex and dynamic relationship between intelligence and cerebral tissue. Yet, there is little information regarding the neuroanatomical correlates of general intelligence in children with epilepsy compared to healthy controls. In vivo imaging techniques, combined with methods for advanced image processing and analysis, offer the potential to examine quantitative mapping of brain development and its abnormalities in childhood epilepsy. A surface-based, computational high resolution 3-D magnetic resonance image analytic technique was used to compare the relationship of cortical thickness with age and intelligence quotient (IQ) in 65 children and adolescents with complex partial seizures (CPS) and 58 healthy controls, aged 6 -18 years. Children were grouped according to health status (epilepsy; controls) and IQ level (average and above; below average) and compared on age-related patterns of cortical thickness. Our cross-sectional findings suggest that disruption in normal age-related cortical thickness expression is associated with intelligence in pediatric CPS patients both with average and below average IQ scores.
PMCID: PMC3117889  PMID: 21586333
Cortical morphometry; IQ; complex partial seizures; cortical thickness; development; childhood
22.  Thought Disorder and Communication Deviance as Predictors of Outcome in Youth at Clinical High Risk for Psychosis 
Given the fundamental role of thought disorder in schizophrenia, subtle communication disturbance may be a valuable predictor of subsequent development of psychosis. Here we examined the contribution of thought and communication disturbance to the prediction of outcome in adolescents identified as putatively prodromal for psychosis.
Transcribed speech samples were elicited from 105 adolescents (54 identified as being at clinical high risk for a first episode of psychosis (CHR) and 51 demographically comparable comparison subjects) and coded for formal thought disorder (FTD) and linguistic cohesion. We then examined the association of baseline FTD/cohesion with conversion to psychosis and social and role outcome at follow-up, approximately one year later.
At baseline, CHR patients who subsequently converted to psychosis (CHR+) showed an elevated rate of illogical thinking and poverty of content (POC) in their speech, relative to both typically developing controls and non-converters (CHR−). CHR+ youth also used significantly less referential cohesion at baseline, indicating that they provide fewer references to people, objects, or events mentioned in preceding utterances. Multiple regression models indicated that, among measures of FTD/cohesion, illogical thinking was uniquely predictive of subsequent conversion to psychosis, whereas POC and referential cohesion were significant predictors of social and role functioning, respectively.
Despite the absence of fully psychotic symptoms, putatively prodromal individuals evidence signs of communication disturbance that are qualitatively similar to those seen in schizophrenia, and are predictive of both conversion to psychosis and psychosocial outcome. These findings suggest that FTD measures have prognostic significance for at-risk youth.
PMCID: PMC3124656  PMID: 21703494
thought disorder; psychosis prodrome; schizophrenia; language; psychosocial outcome
23.  Not All Seizures Are Epilepsy Also Applies to the Military 
Epilepsy Currents  2012;12(4):138-139.
PMCID: PMC3423206  PMID: 22936884
24.  Deformation-based morphometry of prospective neurodevelopmental changes in new onset paediatric epilepsy 
Brain  2011;134(4):1003-1014.
Epilepsy is a prevalent childhood neurological disorder, but there are few prospective quantitative magnetic resonance imaging studies examining patterns of brain development compared to healthy controls. Controlled prospective investigations initiated at or near epilepsy onset would best characterize the nature, timing and course of neuroimaging abnormalities in paediatric epilepsy. In this study, we report the results of a deformation-based morphometry technique to examine baseline and 2-year prospective neurodevelopmental brain changes in children with new and recent onset localization-related epilepsies (n = 24) and idiopathic generalized epilepsies (n = 20) compared to healthy controls (n = 36). Children with epilepsy demonstrated differences from controls in baseline grey and white matter volumes suggesting antecedent anomalies in brain development, as well as abnormal patterns of prospective brain development that involved not only slowed white matter expansion, but also abnormalities of cortical grey matter development involving both greater and lesser volume changes compared to controls. Furthermore, abnormal neurodevelopmental changes extended outside the cortex affecting several subcortical structures including thalamus, cerebellum, brainstem and pons. Finally, there were significant differences between the epilepsy syndromes (localization-related epilepsies and idiopathic generalized epilepsies) with the idiopathic generalized epilepsies group showing a more disrupted pattern of brain structure both at baseline and over the 2-year interval.
PMCID: PMC3069702  PMID: 21398377
MRI; prospective neurodevelopment changes; deformation-based morphometry; new and recent onset epilepsy; localization-related epilepsy; idiopathic generalized epilepsy
25.  Psychiatric and neurodevelopmental disorders in childhood-onset epilepsy 
Epilepsy & behavior : E&B  2011;20(3):550-555.
Childhood-onset epilepsy is associated with psychiatric and cognitive difficulties and with poor social outcomes in adulthood. In a prospective cohort of young people with epilepsy, we studied psychiatric and neurodevelopmental disorders (PD and ND) and epilepsy-related characteristics, all factors which may influence long-term social outcomes. 501 subjects, 159 with complicated (IQ<80 or brain lesion) and 342 with uncomplicated epilepsy were included. PD and ND were more common in complicated epilepsy (p<0.005). In uncomplicated epilepsy, externalizing but not internalizing disorders were strongly associated with ND. Internalizing disorders and ND were associated with lack of 5-year remission. Type of epilepsy was not associated with NDs or PDs. Various comorbid conditions in epilepsy cluster together and are modestly associated with imperfect seizure control. These need to be considered together in evaluating and managing young people with epilepsy and may help explain long-term social outcomes above and beyond poor seizure control.
PMCID: PMC3062749  PMID: 21315660
Co-morbidity; neurodevelopmental disorders; psychiatric disorders; epilepsy; childhood

Results 1-25 (37)