Elevated phase amplitude coupling as a depression biomarker in epilepsy.

Depression is prevalent in epilepsy patients and their intracranial brain activity recordings can be used to determine the types of brain activity that are associated with comorbid depression. We performed case-control comparison of spectral power and phase amplitude coupling (PAC) in 34 invasively monitored drug resistant epilepsy patients' brain recordings. The values of spectral power and PAC for one-minute segments out of every hour in a patient's study were correlated with pre-operative assessment of depressive symptoms by Beck Depression Inventory-II (BDI). We identified an elevated PAC signal (theta-alpha-beta phase (5-25 Hz)/gamma frequency (80-100 Hz) band) that is present in high BDI scores but not low BDI scores adult epilepsy patients in brain regions implicated in primary depression, including anterior cingulate cortex, amygdala and orbitofrontal cortex. Our results showed the application of PAC as a network-specific, electrophysiologic biomarker candidate for comorbid depression and its potential as treatment target for neuromodulation.

Mental health mediators of subjective cognitive concerns among World Trade Center responders.

Decline in cognitive functioning among rescue and recovery workers who responded in the aftermath of the September 11, 2001, World Trade Center (WTC) attacks is of emerging interest. Responders are vulnerable to cognitive decline from exposure to airborne toxins present at the WTC site, as well as from WTC-related mental and physical health conditions. To better understand the relationship between occupational WTC exposure, mental health, physical health and subjective cognitive functioning, we examined the mediating role of health status in the association between exposure and subjective cognitive concerns in a multi-site, longitudinal investigation of the WTC General Responder cohort (n = 16,380 responders; n = 58,575 visits) for the period 2002-2015. Through latent class analyses, we identified a four-level marker of cognitive concerns based on information from a Self-Administered Mental Health Questionnaire. Using generalized linear mixed models with random intercepts, we observed that a higher intensity WTC exposure composite was associated with greater cognitive concerns, and that this association was operating almost entirely through mental health comorbidities, not physical health comorbidities. In fully adjusted models, the inclusion of probable depression, anxiety, PTSD and use of psychotropic medications attenuated the association between highest WTC exposure and greatest cognitive concerns. Physical health did not appear to be on the pathway between WTC exposure and cognitive concerns. Understanding the underlying sources of cognitive concerns may help identify vulnerable members of the General Responder cohort and potentially aid clinical decision-making, such as treatment choice and enhanced screening options. Earlier diagnosis and symptom treatment may help preserve functional independence.

Transforming pediatric neuropsychology through video-based teleneuropsychology: an innovative private practice model pre-COVID-19.

OBJECTIVE: In pediatric neuropsychology multiple barriers such as long wait times until an appointment, insurance coverage, and limited providers who are bilingual/bicultural or who sub-specialize in pediatric neuropsychology, often slow families from receiving diagnoses and interventions in a timely and affordable manner. This paper focuses on increasing accessibility through the development of a video-based, pediatric teleneuropsychology (TeleNP) practice model that was developed in a private practice 2 years before the COVID-19 pandemic. METHOD: 'Design thinking' methodology to problem-solving was utilized to innovate the traditional neuropsychology practice model in under-served areas who may have limited financial and healthcare resources. The practice model approach to include a virtual diagnostic clinic with increased patient and provider efficiency was created to enhance accessibility for patients and sustainability for providers. RESULTS: Video-based TeleNP screenings were conducted for 67 children with developmental (i.e., attention deficit hyperactivity disorder, autism spectrum disorder) and language disorders, as well as concussion and psychiatric diagnoses. Additional comorbidities were identified in 65.6% of children. Follow-up data approximately 2 months later revealed 98.5% of children were receiving new interventions as a result of the video-based TeleNP assessment. CONCLUSION: Video-based TeleNP benefits the consumer as it can reduce wait times, decrease family financial burden (i.e., travel and parent time off work), expedite referrals for interventions, and provide geographically under-served populations access to providers who are linguistically and culturally responsive. For providers, this model revealed improvements with direct implications for cost-saving, thereby facilitating long-term economic sustainability within a private practice healthcare marketplace.

Language mapping using electrocorticography versus stereoelectroencephalography: A case series.

Direct electrical stimulation (DES) is sometimes used in epilepsy surgery to identify areas that may result in language deficits if resected. Extraoperative language mapping is usually performed using electrocorticography (ECOG) - grids and strip electrodes; however, given the better safety profile of stereoelectroencephalogaphy (SEEG), it would be desirable to determine if mapping using SEEG is also effective. We report a case series of fifteen patients that underwent language mapping with either ECOG (5), SEEG (9), or both (1). Six patients in the SEEG group underwent resection or ablation with only mapping via SEEG. No patients in the SEEG group that underwent resective or ablative surgery experienced persistent language deficits. These results suggest that language mapping with SEEG may be considered as a clinically useful alternative to language mapping with ECOG.

Neurocognition and Cerebral Lesion Burden in High-Risk Patients Before Undergoing Transcatheter Aortic Valve Replacement: Insights From the SENTINEL Trial.

OBJECTIVES: The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging. BACKGROUND: TAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease. METHODS: SENTINEL (Cerebral Protection in Transcatheter Aortic Valve Replacement) trial patients had cognitive assessments of attention, processing speed, executive function, and verbal and visual memory. Z-scores were based on normative means and SDs, combined into a primary composite z-score. Brain magnetic resonance images were obtained pre-TAVR on 3-T scanners with a T2 fluid-attenuated inversion recovery (FLAIR) sequence. Scores ≤-1.5 SD below the normative mean (7th percentile) were considered impairment. Paired t tests compared within-subject scores, and chi-square goodness-of-fit compared the percentage of subjects below -1.5 SD. Correlation and regression analyses assessed the relationship between neurocognitive z-scores and T2 lesion volume. RESULTS: Among 234 patients tested, the mean composite z-score was -0.65 SD below the normative mean. Domain scores ranged from -0.15 SD for attention to -1.32 SD for executive function. On the basis of the ≥1.5 SD normative reference, there were significantly greater percentages of impaired scores in the composite z-score (13.2%; p = 0.019), executive function (41.9%; p < 0.001), verbal memory (p < 0.001), and visual memory (p < 0.001). The regression model between FLAIR lesion volume and baseline cognition showed statistically significant negative correlations. CONCLUSIONS: There was a significant proportion of aortic stenosis patients with impaired cognition before TAVR, with a relationship between baseline cognitive function and lesion burden likely attributable to longstanding cerebrovascular disease. These findings underscore the importance of pre-interventional testing and magnetic resonance imaging in any research investigating post-surgical cognitive outcomes in patients with cardiovascular disease.

Synchronization and variability imbalance underlie cognitive impairment in primary-progressive multiple sclerosis.

We aimed to investigate functional connectivity and variability across multiple frequency bands in brain networks underlying cognitive deficits in primary-progressive multiple sclerosis (PP-MS) and to explore how they are affected by the presence of cortical lesions (CLs). We analyzed functional connectivity and variability (measured as the standard deviation of BOLD signal amplitude) in resting state networks (RSNs) associated with cognitive deficits in different frequency bands in 25 PP-MS patients (12 M, mean age 50.9 ± 10.5 years) and 20 healthy subjects (9 M, mean age 51.0 ± 9.8 years). We confirmed the presence of a widespread cognitive deterioration in PP-MS patients, with main involvement of visuo-spatial and executive domains. Cognitively impaired patients showed increased variability, reduced synchronicity between networks involved in the control of cognitive macro-domains and hyper-synchronicity limited to the connections between networks functionally more segregated. CL volume was higher in patients with cognitive impairment and was correlated with functional connectivity and variability. We demonstrate, for the first time, that a functional reorganization characterized by hypo-synchronicity of functionally-related/hyper-synchronicity of functionally-segregated large scale networks and an abnormal pattern of neural activity underlie cognitive dysfunction in PP-MS, and that CLs possibly play a role in variability and functional connectivity abnormalities.

A consecutive case series experience with [18 F] florbetapir PET imaging in an urban dementia center: impact on quality of life, decision making, and disposition.

BACKGROUND: Identification and quantification of fibrillar amyloid in brain using positron emission tomography (PET) imaging and Amyvid™ ([18 F] Amyvid, [18 F] florbetapir, 18 F-AV-45) was recently approved by the US Food and Drug Administration as a clinical tool to estimate brain amyloid burden in patients being evaluated for cognitive impairment or dementia. Imaging with [18 F] florbetapir offers in vivo confirmation of the presence of cerebral amyloidosis and may increase the accuracy of the diagnosis and likely cause of cognitive impairment (CI) or dementia. Most importantly, amyloid imaging may improve certainty of etiology in situations where the differential diagnosis cannot be resolved on the basis of standard clinical and laboratory criteria. RESULTS: A consecutive case series of 30 patients (age 50-89; 16 M/14 F) were clinically evaluated at a cognitive evaluation center of urban dementia center and referred for [18 F] florbetapir PET imaging as part of a comprehensive dementia workup. Evaluation included neurological examination and neuropsychological assessment by dementia experts. [18 F] florbetapir PET scans were read by trained nuclear medicine physicians using the qualitative binary approach. Scans were rated as either positive or negative for the presence of cerebral amyloidosis. In addition to a comprehensive dementia evaluation, post [18 F] florbetapir PET imaging results caused diagnoses to be changed in 10 patients and clarified in 9 patients. Four patients presenting with SCI were negative for amyloidosis. These results show that [18 F] florbetapir PET imaging added diagnostic clarification and discrimination in over half of the patients evaluated. CONCLUSIONS: Amyloid imaging provided novel and essential data that: (1) caused diagnosis to be revised; and/or (2) prevented the initiation of incorrect or suboptimal treatment; and/or (3) avoided inappropriate referral to an anti-amyloid clinical trial.

Neuropsychological endophenotypes in ADHD with and without epilepsy.

Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity in children with epilepsy. Despite similarities in behavioral manifestations of inattention and hyperactivity, it is unclear whether the neuropsychological endophenotypes of children with developmental ADHD differ from those with ADHD in the context of epilepsy. The present study compared groups of clinically referred children with both ADHD-Inattentive subtype (ADHD-I) and ADHD-Combined subtype (ADHD-C) to children with ADHD-I and ADHD-C and epilepsy on neuropsychological measures of intellectual functioning, auditory attention, working memory, and sustained attention and response inhibition. Those with ADHD and epilepsy performed more poorly on measures of intellectual function (e.g., Full-Scale IQ, Verbal IQ, Performance IQ) as well as auditory attention and working memory. Differences across the groups were also seen on a continuous performance test. Follow-up correlational analyses showed that variables such as seizure frequency and number of antiepilepsy medications predicted cognitive dysfunction in the epilepsy groups. Overall results suggest that the neuropsychological endophenotypes in developmental ADHD versus ADHD in epilepsy differ with seizure-related variables predicting cognitive dysfunction.

The clinical utility of the Social Responsiveness Scale and Social Communication Questionnaire in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is often associated with epilepsy, mental retardation, and autism spectrum disorders (ASDs). Thus, screening for ASDs is important when evaluating these individuals. We examined the utility of the Social Responsiveness Scale (SRS) and Social Communication Questionnaire (SCQ), two measures for screening for ASDs, in a TSC population. Twenty-one children were evaluated, with 52.4% classified as having ASDs on the SRS and 42.9% classified as such on the SCQ. Number of antiepileptic drugs significantly correlated with SRS Total score, as did level of intellectual functioning. Evidence for convergent validity was obtained between the SRS and SCQ Total scores (r=0.605). Moreover, all SRS subscales correlated with SCQ Total score (r>0.400). All SCQ subscales except for Communication correlated with SRS total. Overall, the results demonstrate that these questionnaires appear to be effective screens for ASDs in a TSC population and are measuring similar constructs.

Fatigue and quality of life in pediatric multiple sclerosis.

Fatigue and quality of life are significant concerns in adult multiple sclerosis (MS) but little is known about these factors in pediatric MS. The present investigation evaluates fatigue and quality of life in 51 pediatric MS patients to determine the rate of fatigue and reduced quality of life and assesses the relations between these variables and clinical factors. Fatigue and quality of life were assessed by self- and parent-report via the PedsQL Multidimensional Fatigue Scale and the PedsQL Quality of Life Scale. One-sample t-tests determined if scores were below published data for healthy individuals. Moreover, scores falling one standard deviation from norms were considered mildly affected, with severe difficulties being defined as scores falling two or more standard deviations from norms. Associations between self- and parent-reported difficulties and clinical factors were examined via Pearson correlation analyses. In comparison with healthy samples, pediatric MS patients reported greater difficulties with respect to fatigue, sleep, cognition, physical limitations, and academics. In addition to significant difficulties on these factors, parents reported problems with respect to emotional functioning, and tended to report greater fatigue, sleep, and cognitive difficulties than were self-reported. Expanded Disability Status Scale score was the only neurologic variable significantly related to fatigue or quality of life scores. Fatigue was significantly correlated with reports of sleep difficulties, cognitive problems, and quality of life variables. These findings suggest that fatigue and poorer quality of life is a clear concern in pediatric MS, and is related to overall physical disability.

Diagnostic validity of a neuropsychological test battery for Hispanic patients with epilepsy.

The Neuropsychological Screening Battery for Hispanics (NeSBHIS) was developed to address the growing need for linguistically appropriate Spanish-language assessment measures. Despite the potential benefits to clinical practice, no prior study has assessed its diagnostic validity in populations with epilepsy. One hundred and fifteen patients with confirmed epilepsy were evaluated via the NeSBHIS; these data were standardized according to age- and education-based norms. Performance decrements were observed in more than 40% of participants on measures of processing speed and naming. Deficits in verbal and visual recall were also exhibited by 29 and 26% of the sample, respectively. No significant differences in test performance emerged between patients with VEEG evidence of left (N=48) versus right (N=24) temporal lobe epilepsy. Although the NeSBHIS is sensitive to the cognitive impairments commonly observed in populations with epilepsy, there are limitations to its ability to identify lateralized neuropsychological impairment in patients with temporal lobe epilepsy.

Assessing effort during neuropsychological evaluation with the TOMM in children and adolescents with epilepsy.

Effort assessment is of particular importance in pediatric epilepsy where neuropsychological findings may influence treatment decisions, especially if surgical interventions are being considered. The present investigation examines the Test of Memory Malingering (TOMM) in 60 children and adolescents with epilepsy. The overall pass rate for the sample was 90%. TOMM scores were unrelated to age, though there was a significant correlation between TOMM Trial 2 scores and intelligence estimates. Overall, the TOMM appears to be a valid measure of effort in young epilepsy patients, though caution should be used when interpreting scores for those with very low IQ, especially if behavioral problems are also evident. Caution should also be exercised in interpreting scores in children with ongoing interictal epileptiform activity that may disrupt attention.

Neuropsychologic performance of children with epilepsy on the NEPSY.

Neuropsychologic test scores from a group of children with epilepsy were compared to the standardization sample of the NEPSY: A Developmental Neuropsychological Assessment, a relatively new neuropsychologic testing instrument. Nineteen children with a confirmed diagnosis of epilepsy (11 boys, 8 girls), aged 3-12 years, participated. Attention/executive function, language, sensorimotor, visuospatial, and learning/memory domain scores were examined, as well as individual subtest scores. The mean scores on the attention/executive function, language, and sensorimotor domains were >1.5 standard deviations below the normative mean, and significantly lower than the mean visuospatial domain score (P < 0.05). The mean language domain score was also significantly lower than the learning/memory score (P < 0.05). Mean subdomain scores varied, with impairment on two tasks measuring rapid automatic processing and graphomotor precision, respectively. On the majority of subtests, 15% or more of the sample scored in the impaired range. Associations between patient age, seizure onset age, seizure frequency, and antiepileptic medication status were not associated with outcome, perhaps due in part to the small sample size. The strengths and weaknesses of the NEPSY as a measure of neuropsychologic functioning in children with epilepsy, and its utility in highlighting risks to academic achievement are discussed.

Sustained attention and response inhibition in young children at risk for Attention Deficit/Hyperactivity Disorder.

BACKGROUND: Studies of school-aged children, adolescents, and adults with Attention Deficit/Hyperactivity Disorder (ADHD) have variably shown ADHD-related impairment in both inhibitory control and sustained attention. However, few studies have examined ADHD-associated patterns of performance on these tasks among younger children (below age 7 years). METHODS: A combined continuous performance test and go/no-go task (CPT/GNG) and the Day-Night Stroop Task (DNST) were administered to an ethnically diverse sample of 3.44- to 6.95-year-old children rated by parents and teachers as being either high risk or low risk for ADHD. All children performed the DNST (N = 71) and a subset of the sample (N = 44) performed the CPT/GNG. Analyses assessed task validity as well as the effects of age and risk status. RESULTS: Significant main effects for age and risk status were found on all tasks. In addition, age x condition interactions were found for the CPT and DNST, which suggest that the tasks were sensitive to age-related changes in sustained attention and inhibitory control respectively. No significant risk status x condition interactions were found, suggesting that young children at risk for ADHD do not exhibit specific deficits in either inhibitory control or sustained attention. The most consistent effect related to risk status across tasks was the greater number of errors and longer and more variable reaction times on the part of children at risk for ADHD irrespective of condition. CONCLUSIONS: ADHD-associated decrements in performance on these tasks appear to be attributable either to generalized behavioral dysregulation or poor state regulation rather than to deficient inhibitory control.