Study of the Relationship Between Ultrasound Strain Indices and Cognitive Decline for Vulnerable Carotid Plaque.

A relationship between ultrasound strain indices in carotid plaque to cognitive domains of executive and language function are studied in 42 symptomatic and 34 asymptomatic patients. The mean and standard deviation of the percentage stenosis were 72.10 ± 15.19 and 77.41 ± 11.20 for symptomatic and asymptomatic patients respectively. Pearson's correlation between axial, lateral and shear strain indices versus executive and language composite scores was performed.. A significant inverse correlation for both executive and language function for symptomatic patients to strain indices was found. On the other hand, for asymptomatic patients only executive function was inversely correlated with the corresponding strain indices. Our hypothesis that microemboli from vulnerable plaque and possible 'silent strokes' may be responsible for decline in executive function for both symptomatic and asymptomatic patients'. Strokes and transient ischemic attacks may be responsible for further cognitive decline in language function for symptomatic patients.

Contribution of Family Relatedness to Neurobehavioral Comorbidities in Idiopathic Childhood Epilepsies.

OBJECTIVES: Rates of cognitive, academic and behavioral comorbidities are elevated in children with epilepsy. The contribution of environmental and genetic influences to comorbidity risk is not fully understood. This study investigated children with epilepsy, their unaffected siblings, and controls to determine the presence and extent of risk associated with family relatedness across a range of epilepsy comorbidities. METHODS: Participants were 346 children (8-18 years), n=180 with recent-onset epilepsy, their unaffected siblings (n=67), and healthy first-degree cousin controls (n=99). Assessments included: (1) Child Behavior Checklist/6-18 (CBCL), (2) Behavior Rating Inventory of Executive Function (BRIEF), (3) history of education and academic services, and (4) lifetime attention deficit hyperactivity disorder (ADHD) diagnosis. Analyses consisted of linear mixed effect models for continuous variables, and logistic mixed models for binary variables. RESULTS: Differences were detected between the three groups of children across all measures (p<.001). For ADHD, academic problems, and executive dysfunction, children with epilepsy exhibited significantly more problems than unaffected siblings and controls; siblings and controls did not differ statistically significantly from each other. For social competence, children with epilepsy and their unaffected siblings displayed more abnormality compared with controls, with no statistically significant difference between children with epilepsy and unaffected siblings. For behavioral problems, children with epilepsy had more abnormality than siblings and controls, but unaffected siblings also exhibited more abnormalities than controls. CONCLUSIONS: The contribution of epilepsy and family relatedness varies across specific neurobehavioral comorbidities. Family relatedness was not significantly associated with rates of ADHD, academic problems and executive dysfunction, but was associated with competence and behavioral problems. (JINS, 2018, 24, 653-661).

The Preservation of Cognition 1 Year After Carotid Endarterectomy in Patients With Prior Cognitive Decline.

BACKGROUND: Vascular cognitive decline is critically important in the course of atherosclerosis and stroke. OBJECTIVE: To explore the hypothesis that carotid endarterectomy (CEA) by removing an unstable plaque may slow the course of vascular cognitive decline in both symptomatic and asymptomatic patients. METHODS: Patients with clinically significant (>60%) carotid stenosis were studied preop and 1 yr post-CEA for clinical symptoms, vascular cognitive decline, instability of carotid plaque-presence of microemboli, brain white matter changes, and medical risk factors. RESULTS: Forty-six percent were classically symptomatic. All patients showed vascular cognitive decline at presentation which correlated with degree of plaque instability. Significant white matter hyperintensity changes (48.7%) and cerebral emboli (25%) were also seen at baseline in both classically symptomatic and asymptomatic. One year after CEA, both groups showed no decline in cognitive function and significant improvement in 2 tests (P = .028 and P = .013). Brain white matter hyperintensities were unchanged. Microemboli were reduced but remained present (17.86%). Improvement was predicted by the presence of hypertension (P = .001), or less advanced cognitive decline preoperatively (P = .009). CONCLUSION: This study demonstrates the importance of vascular cognitive decline in atherosclerotic disease. This is a function of the degree of instability of the atherosclerotic plaque more than the presence of stroke symptoms. It further suggests that atherosclerotic vascular cognitive decline need not be inevitable, and may be modified by treating hypertension and removal of the unstable plaque. This highlights the need for continued research on the cognitive effects of cerebrovascular disease and the synergistic benefits of intensive medical and surgical therapy.

Carotid atherosclerotic plaque instability and cognition determined by ultrasound-measured plaque strain in asymptomatic patients with significant stenosis.

OBJECTIVE This article describes the use of ultrasound measurements of physical strain within carotid atherosclerotic plaques as a measure of instability and the potential for vascular cognitive decline, microemboli, and white matter changes. METHODS Asymptomatic patients with significant (> 60%) carotid artery stenosis were studied for dynamic measures of plaque instability, presence of microemboli, white matter changes, and vascular cognitive decline in comparison with normative controls and premorbid state. RESULTS Although classically asymptomatic, these patients showed vascular cognitive decline. The degree of strain instability measured within the atherosclerotic plaque directly predicted vascular cognitive decline in these patients thought previously to be asymptomatic according to classic criteria. Furthermore, 26% of patients showed microemboli, and patients had twice as much white matter hyperintensity as controls. CONCLUSIONS These data show that physical measures of plaque instability are possible through interpretation of ultrasound strain data during pulsation, which may be more clinically relevant than solely measuring degree of stenosis. The data also highlight the importance of understanding that the definition of symptoms should not be limited to motor, speech, and vision function but underscore the role of vascular cognitive decline in the pathophysiology of carotid atherosclerotic disease. Clinical trial registration no.: NCT02476396 (clinicaltrials.gov).

Student use and perceptions of mobile technology in clinical clerkships - Guidance for curriculum design.

BACKGROUND: We examined the types of technology used by medical students in clinical clerkships, and the perception of technology implementation into the curriculum. METHODS: An online survey about technology use was completed prior to general surgery clinical clerkship. Types of devices and frequency/comfort of use were recorded. Perceptions of the benefits and barriers to technology use in clerkship learning were elicited. RESULTS: 125/131 (95.4%) students responded. Most students owned a smart phone (95.2%), tablet (52.8%), or both (50%); 61.6% spent > 11 h/week learning on a device at the Johns Hopkins School of Medicine for educational purposes. Technology use was seen as beneficial by 97.6% of students. Classes that used technology extensively were preferred by 54% of students, although 47.2% perceived decreased faculty/classmate interaction. CONCLUSIONS: Students use mobile technology to improve how they learn new material, and prefer taking classes that incorporate information technology. However, in-person/blended curricula are preferable to completely online courses.

Control groups in paediatric epilepsy research: do first-degree cousins show familial effects?

To determine whether first-degree cousins of children with idiopathic focal and genetic generalized epilepsies show any association across measures of cognition, behaviour, and brain structure. The presence/absence of associations addresses the question of whether and to what extent first-degree cousins may serve as unbiased controls in research addressing the cognitive, psychiatric, and neuroimaging features of paediatric epilepsies. Participants were children (aged 8-18) with epilepsy who had at least one first-degree cousin control enrolled in the study (n=37) and all enrolled cousin controls (n=100). Participants underwent neuropsychological assessment and brain imaging (cortical, subcortical, and cerebellar volumes), and parents completed the Child Behaviour Checklist (CBCL). Data (based on 42 outcome measures) from cousin controls were regressed on the corresponding epilepsy cognitive, behavioural, and imaging measures in a linear mixed model and case/control correlations were examined. Of the 42 uncorrected correlations involving cognitive, behavioural, and neuroimaging measures, only two were significant (p<0.05). The median correlation was 0.06. A test for whether the distribution of p values deviated from the null distribution under no association was not significant (p>0.25). Similar results held for the cognition/behaviour and brain imaging measures separately. Given the lack of association between cases and first-degree cousin performances on measures of cognition, behaviour, and neuroimaging, the results suggest a non-significant genetic influence on control group performance. First-degree cousins appear to be unbiased controls for cognitive, behavioural, and neuroimaging research in paediatric epilepsy.

Histopathologic Validation of Grayscale Carotid Plaque Characteristics Related to Plaque Vulnerability.

Inflammation and angiogenesis play major roles in carotid plaque vulnerability. The purpose of this study was to determine whether gray-scale features of carotid plaques are associated with histologic markers for inflammation. Thirty-eight individuals completed a dedicated research carotid ultrasound exam before carotid endarterectomy. Gray-scale analysis was performed on plaque images to measure plaque echogenicity (gray-scale median [GSM] pixel brightness), plaque area, presence of discrete white areas (DWAs) and the percent of black area near the lumen on any one component of the plaque. Plaques with higher ultrasound GSM had greater percent calcification (p = 0.013) on histopathology. Presence of an ultrasound DWA was associated with more plaque hemosiderin (p = 0.0005) and inflammation (p = 0.019) on histopathology examination. The percent of plaque black area in any one component was associated with a higher score for macroscopic ulceration (p = 0.028). Ultrasound plaque characteristics (GSM, DWAs and black areas) represent histopathologic markers associated with plaque vulnerability. ClinicalTrials.gov identifier: NCT02476396.

Disruptions in cortico-subcortical covariance networks associated with anxiety in new-onset childhood epilepsy.

Anxiety disorders represent a prevalent psychiatric comorbidity in both adults and children with epilepsy for which the etiology remains controversial. Neurobiological contributions have been suggested, but only limited evidence suggests abnormal brain volumes particularly in children with epilepsy and anxiety. Since the brain develops in an organized fashion, covariance analyses between different brain regions can be investigated as a network and analyzed using graph theory methods. We examined 46 healthy children (HC) and youth with recent onset idiopathic epilepsies with (n = 24) and without (n = 62) anxiety disorders. Graph theory (GT) analyses based on the covariance between the volumes of 85 cortical/subcortical regions were investigated. Both groups with epilepsy demonstrated less inter-modular relationships in the synchronization of cortical/subcortical volumes compared to controls, with the epilepsy and anxiety group presenting the strongest modular organization. Frontal and occipital regions in non-anxious epilepsy, and areas throughout the brain in children with epilepsy and anxiety, showed the highest centrality compared to controls. Furthermore, most of the nodes correlating to amygdala volumes were subcortical structures, with the exception of the left insula and the right frontal pole, which presented high betweenness centrality (BC); therefore, their influence in the network is not necessarily local but potentially influencing other more distant regions. In conclusion, children with recent onset epilepsy and anxiety demonstrate large scale disruptions in cortical and subcortical brain regions. Network science may not only provide insight into the possible neurobiological correlates of important comorbidities of epilepsy, but also the ways that cortical and subcortical disruption occurs.

Cognitive phenotypes in childhood idiopathic epilepsies.

OBJECTIVE: The objective of this study was to identify cognitive phenotypes in children with new-onset focal and generalized idiopathic epilepsies and determine their relationship with epilepsy syndrome, brain structure, neurodevelopmental history, and family characteristics. METHODS: One hundred thirty-eight children with new-onset epilepsy and 95 controls (age: 8-18) underwent neuropsychological, clinical, and quantitative MR evaluations. Control participants' neuropsychological data were subjected to confirmatory factor analysis and then resultant factor scores were applied to participants with epilepsy and subjected to latent class analysis. Identified cognitive phenotypes were examined in relation to epilepsy syndrome, quantitative neuroimaging, and familial and neurodevelopmental variables. RESULTS: Confirmatory factor analysis identified five cognitive factors (verbal, perceptual, speed, attention, executive), and latent class analysis identified three clusters of participants with epilepsy: 1) average and similar to controls, 2) mild impairment across multiple cognitive domains, and 3) impairment across all domains with severe attentional impairment, representing 44%, 44%, and 12% of the epilepsy sample, respectively. Cognitive phenotype membership was not associated with epilepsy syndrome but was associated with increasing abnormalities in brain structure, parental IQ, and features of early developmental history. SIGNIFICANCE: Cognitive phenotypes are present in idiopathic childhood epilepsies that are unassociated with traditional epilepsy syndromes but are associated with measures of brain structure, family history, and neurodevelopmental features.

Classification of Symptomatic and Asymptomatic Patients with and without Cognitive Decline Using Non-invasive Carotid Plaque Strain Indices as Biomarkers.

Vascular cognitive decline may be caused by micro-emboli generated by carotid plaque instability. We previously found that maximum strain indices in carotid plaque were significantly correlated with cognitive function. In the work described here, we examined these associations with a larger sample size, as well as evaluated the performance of these maximum strain indices in predicting cognitive impairment. Ultrasound-based strain imaging and cognition assessment were conducted on 75 human patients. Patients underwent one of two standardized cognitive test batteries, either the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) or the National Institute of Neurologic Disorder and Stroke-Canadian Stroke Network (NINDS-CSN) Vascular Cognitive Impairment Harmonization Standards (60 min). Scores were standardized within each battery to allow these data to be combined across all participants. Radiofrequency signals for ultrasound strain imaging were acquired on the carotid arteries using either a Siemens Antares with a VFX 13-5 linear array transducer or a Siemens S2000 with an 18 L6 linear array transducer. The same hierarchical block-matching motion tracking algorithm developed in our laboratory was used to estimate accumulated axial, lateral, and shear strain indices in carotid plaque, with inclusion of adventitia regardless of the ultrasound system and transducer used. Associations between cognitive z-scores and maximum strain indices were examined using Pearson's correlation coefficients. Maximum strain indices were also employed to predict cognitive impairment using receiver operating characteristic analysis. All correlations between maximum strain indices and total cognition were statistically significant (p < 0.05), indicating that these indices have good utility in predicting cognitive impairment. Maximum lateral strain indices provided an area under the curve of 0.85 for symptomatic patients and 0.68 for asymptomatic patients. Our results indicate the important relationship of maximum strain indices to cognitive function and the feasibility of using maximum strain indices to predict cognitive decline with inclusion of the adventitia layer into the segmentation of plaque.

Correlation of EEG with neuropsychological status in children with epilepsy.

OBJECTIVE: To determine correlations of the EEG frequency spectrum with neuropsychological status in children with idiopathic epilepsy. METHODS: Forty-six children ages 8-18 years old with idiopathic epilepsy were retrospectively identified and analyzed for correlations between EEG spectra and neuropsychological status using multivariate linear regression. In addition, the theta/beta ratio, which has been suggested as a clinically useful EEG marker of attention-deficit hyperactivity disorder (ADHD), and an EEG spike count were calculated for each subject. RESULTS: Neuropsychological status was highly correlated with posterior alpha (8-15 Hz) EEG activity in a complex way, with both positive and negative correlations at lower and higher alpha frequency sub-bands for each cognitive task in a pattern that depends on the specific cognitive task. In addition, the theta/beta ratio was a specific but insensitive indicator of ADHD status in children with epilepsy; most children both with and without epilepsy have normal theta/beta ratios. The spike count showed no correlations with neuropsychological status. CONCLUSIONS: (1) The alpha rhythm may have at least two sub-bands which serve different purposes. (2) The theta/beta ratio is not a sensitive indicator of ADHD status in children with epilepsy. (3) The EEG frequency spectrum correlates more robustly with neuropsychological status than spike count analysis in children with idiopathic epilepsy. SIGNIFICANCE: (1) The role of posterior alpha rhythms in cognition is complex and can be overlooked if EEG spectral resolution is too coarse or if neuropsychological status is assessed too narrowly. (2) ADHD in children with idiopathic epilepsy may involve different mechanisms from those in children without epilepsy. (3) Reliable correlations with neuropsychological status require longer EEG samples when using spike count analysis than when using frequency spectra.

Cognitive Deficits in Symptomatic and Asymptomatic Carotid Endarterectomy Surgical Candidates.

The role played by vessel disease in stroke-related cognition dysfunction is unclear. We assessed the impact of significant atherosclerotic disease on cognition-even in patients asymptomatic for stroke. We hypothesized that patients would perform poorly relative to controls, but that symptomatic/asymptomatic status (history of stroke/transient ischemic attack) would have no effect. Fifty-two carotid endarterectomy candidates with >60% carotid stenosis and 17 controls underwent a 60-min neuropsychological test protocol. Symptomatic and asymptomatic patients showed deficits in executive function, delayed verbal recall, and general knowledge. Patients symptomatic for stroke also performed worse on tests of language and motor/visuomotor ability. Symptomatic and asymptomatic patients differed in working memory and language task performance. Although all patients showed deficits in executive function and memory, only symptomatic patients showed additional deficits in language and motor function. Cognitive abnormalities in patients viewed as "asymptomatic" for stroke underscore the need for early identification and treatment.

The relationship between carotid artery plaque stability and white matter ischemic injury.

Higher local carotid artery strain has previously been shown to be a characteristic of unstable carotid plaques. These plaques may be characterized by microvascular changes that predispose to intraplaque hemorrhage, increasing the likelihood of embolization. Little is known however, about how these strain indices correspond with imaging markers of brain health and metrics of brain structure. White matter hyperintensities (WMHs), which are bright regions seen on T2-weighted brain MRI imaging, are postulated to result from cumulative ischemic vascular injury. Consequently, we hypothesized that plaques that are more prone to microvascular changes and embolization, represented by higher strain indices on ultrasound, would be associated with an increased amount of WMH lesion volume. This relationship would suggest not only emboli as a cause for the brain degenerative changes, but more importantly, a common microvascular etiology for large and small vessel contributions to this process. Subjects scheduled to undergo a carotid endarterectomy were recruited from a neurosurgery clinic. Prior to surgery, participating subjects underwent both ultrasound strain imaging and brain MRI scans as part of a larger clinical study on vascular health and cognition. A linear regression found that maximum absolute strain and peak to peak strain in the surgical side carotid artery were predictive of WMH burden. Furthermore, the occurrence of microembolic signals monitored using transcranial Doppler (TCD) ultrasound examinations also correlated with increasing lesion burden. It is becoming increasingly recognized that cognitive decline is often multifactorial in nature. One contributing extra-brain factor may be changes in the microvasculature that produce unstable carotid artery plaques. In this study, we have shown that higher strain indices in carotid artery plaques are significantly associated with an increased WMH burden, a marker of vascular mediated brain damage.

Cognition and brain development in children with benign epilepsy with centrotemporal spikes.

OBJECTIVE: Benign epilepsy with centrotemporal spikes (BECTS), the most common focal childhood epilepsy, is associated with subtle abnormalities in cognition and possible developmental alterations in brain structure when compared to healthy participants, as indicated by previous cross-sectional studies. To examine the natural history of BECTS, we investigated cognition, cortical thickness, and subcortical volumes in children with new/recent onset BECTS and healthy controls (HC). METHODS: Participants were 8-15 years of age, including 24 children with new-onset BECTS and 41 age- and gender-matched HC. At baseline and 2 years later, all participants completed a cognitive assessment, and a subset (13 BECTS, 24 HC) underwent T1 volumetric magnetic resonance imaging (MRI) scans focusing on cortical thickness and subcortical volumes. RESULTS: Baseline cognitive abnormalities associated with BECTS (object naming, verbal learning, arithmetic computation, and psychomotor speed/dexterity) persisted over 2 years, with the rate of cognitive development paralleling that of HC. Baseline neuroimaging revealed thinner cortex in BECTS compared to controls in frontal, temporal, and occipital regions. Longitudinally, HC showed widespread cortical thinning in both hemispheres, whereas BECTS participants showed sparse regions of both cortical thinning and thickening. Analyses of subcortical volumes showed larger left and right putamens persisting over 2 years in BECTS compared to HC. SIGNIFICANCE: Cognitive and structural brain abnormalities associated with BECTS are present at onset and persist (cognition) and/or evolve (brain structure) over time. Atypical maturation of cortical thickness antecedent to BECTS onset results in early identified abnormalities that continue to develop abnormally over time. However, compared to anatomic development, cognition appears more resistant to further change over time.

Brief clinical screening for academic underachievement in new-onset childhood epilepsy: utility and longitudinal results.

OBJECTIVE: This study was conducted to determine the lifetime rate and distribution of supportive academic and educational services provided to children with new- or recent-onset epilepsy and typically developing controls, the relationship of this history to objective academic test performance, and the course of performance over serial evaluations (baseline and 2 and 5years later). METHODS: Research participants were 91 children aged 8-18 at study entry, including 50 youth with recent-onset epilepsy (28 focal [FE] and 22 generalized [GE] epilepsy) and healthy first-degree cousin controls (n=41). The sample with epilepsy included children with uncomplicated epilepsy and normal imaging and development. Lifetime history of a diversity of supportive educational services was determined via a structured interview with parents at the baseline study visit. Associations were examined between these support services and participants' academic performance in reading, spelling, and arithmetic (Wide Range Achievement Test-Revision 3 [WRAT3] [12]) during three serial study visits including baseline and 2 and 5years later. RESULTS: Children with epilepsy had a higher lifetime rate of provision of diverse academic supportive services compared to controls at the baseline visit (52% vs. 18%). These services antedated epilepsy diagnosis in the majority (80.8%) of the children with epilepsy. Among children with epilepsy, children who presented with academic services had significantly lower WRAT3 reading, spelling, and arithmetic performance at baseline and at 2- and 5-year follow-ups. CONCLUSION: A brief structured clinical interview conducted with parents identifies children with epilepsy who are at academic risk at the time of diagnosis, with that risk persisting up to 5years later.

Children with epilepsy and anxiety: Subcortical and cortical differences.

OBJECTIVE: Using a hypothesis-driven approach, subcortical and cortical regions implicated in anxiety disorders in the general population were examined in children with recent-onset epilepsy with versus without anxiety compared to controls. This study reports frequency of anxiety disorders while examining familial, clinical, and demographic variables associated with anxiety in children with epilepsy. METHOD: Participants included 88 children with epilepsy aged 8-18 years: 25 with a current anxiety disorder and 63 children with epilepsy and no current anxiety disorder. Forty-nine controls without anxiety disorders were included. T1 volumetric magnetic resonance imaging (MRI) scans were collected; subcortical volumes and cortical thickness were computed using the FreeSurfer image analysis suite. Analyses focused on adjusted measures of subcortical volumes and cortical thickness. RESULTS: Relative to controls, larger left amygdala volumes were found in the Epilepsy with Anxiety group compared to the Epilepsy without Anxiety group (p = 0.027). In the hippocampus, there were no significant differences between groups. Examination of cortical thickness demonstrated that the Epilepsy with Anxiety group showed thinning in left medial orbitofrontal (p = 0.001), right lateral orbitofrontal (p = 0.017), and right frontal pole (p = 0.009). There were no differences between groups in age, sex, IQ, age of onset, medications, or duration of epilepsy. There were more family members with a history of anxiety disorders in the Epilepsy with Anxiety group compared to the Epilepsy without Anxiety group (p = 0.005). SIGNIFICANCE: Anxiety is a common psychiatric comorbidity in children with recent-onset epilepsy with volumetric enlargement of the amygdala and thinner cortex in orbital and other regions of prefrontal cortex, suggesting structural abnormalities in brain regions that are part of the dysfunctional networks reported in individuals with anxiety disorders in the general population. These findings are evident early in the course of epilepsy, are not related to chronicity of seizures, and may be linked to a family history of anxiety and depressive disorders.

Longitudinal trajectories of behavior problems and social competence in children with new onset epilepsy.

AIM: To characterize the prospective trajectory of parent-reported behavior and social competence problems in children with new or recent onset epilepsy from diagnosis to 5 to 6 years after diagnosis compared to healthy control participants. METHOD: Thirty-five children (21 males, 14 females; mean age 14y 1mo [SD 3y 4mo] range 8-18y) with new/recent onset idiopathic generalized (IGE) and 34 children with localization-related epilepsies (LRE; 19 males, 15 females; mean age 10y 8mo [SD 2y 2mo] range 8-18y) underwent behavioral assessment (Child Behavior Checklist) at baseline, 2 years, and 5 to 6 years after diagnosis. The assessment comprised the summary scales Total Behavior Problems Internalizing Problems, Externalizing Problems, and Total Competence. Sixty-two children with normal development served as comparison participants. Analyses were based on random effects regression modeling comparing trajectories with respect to time since epilepsy diagnosis among groups. RESULTS: Differences in parent-reported behavioral problems between LRE and IGE syndrome groups and healthy comparison participants were detectable at or near the time of diagnosis and remained either stable (competence) or tended to abate (behavior problems) over the ensuing 5 to 6 years without evidence of progressive worsening. These trends were evident for both LRE and IGE groups, with no differences between them. INTERPRETATION: Behavior and competence problems in children with LRE and IGE are not characterized by progressive worsening over a 5- to 6-year period. Behavioral problems are present near the time of diagnosis and tend to abate over time, with competence problems being more persistent across serial assessments, and present in both LRE and IGE groups.

Neurodevelopment in new-onset juvenile myoclonic epilepsy over the first 2 years.

OBJECTIVE: Adults with juvenile myoclonic epilepsy (JME) have subtle brain structural abnormalities in the frontothalamocortical network, poorer cognitive function, and worse long-term social outcomes, even when their seizures are controlled and/or remitted. The natural history of JME and development of abnormalities in brain structure and cognition from epilepsy onset has not been studied. METHODS: The maturational trajectories of cognitive and brain development were prospectively compared between 19 children with new-onset JME in the first 2 years after diagnosis and 57 healthy controls. RESULTS: Cognitive abilities of children with JME were similar to or worse than healthy controls at baseline but failed to reach the competence level of healthy controls at follow-up across most of the tested cognitive abilities. Abnormal patterns of brain development, as assessed by magnetic resonance imaging studies, were evident in children with JME and included attenuation of age-related decline in cortical volume, thickness, and surface area compared to typically developing children. The altered brain developmental trajectory in the JME group was evident in higher-association frontoparietotemporal brain regions (p < 0.05, corrected for multiple comparisons). INTERPRETATION: Children with JME have abnormal structural brain development and impaired cognitive development early in the course of their epilepsy.