Cognitive function in pediatric-onset relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

INTRODUCTION: Myelin oligodendrocyte glycoprotein antibodies are identified in approximately 30-50% of youth with pediatric-onset acquired demyelinating syndromes. Little is known about the cognitive sequelae of relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) with onset in childhood or adolescence.Overall, adults had 41% more risk than children to relapse over the whole disease course Overall, adults had 41% more risk than children to relapse over the whole disease course OBJECTIVE: To compare cognitive performance in participants with pediatric-onset relapsing MOGAD, pediatric-onset multiple sclerosis (POMS), and age-matched healthy controls. METHODS: The Penn Computerized Neurocognitive Battery (PCNB) was administered to 12 individuals with relapsing MOGAD (age = 16.3 ± 4.8 years; 75% female; disease duration = 8.1 ± 2.7 years), 68 individuals with POMS (age = 18.3 ± 4.0 years; 72% female; disease duration = 3.8 ± 3.9 years), and 108 healthy controls (age = 17.0 ± 4.9 years; 68.5% female). Accuracy was assessed on four domains: Executive Function, Episodic Memory, Complex Cognition, Social Cognition; and overall response time (RT) and RT across three factors (i.e., Time Constrained, Open-Window, Memory). Global performance was determined by a composite score. Multiple linear regression was used to examine group differences on PCNB domain and factor z-scores, controlling for age and sex. We also covaried disease duration for relapsing MOGAD vs. POMS analyses. RESULTS: Relative to healthy controls, relapsing MOGAD participants were less accurate on the Complex Cognition domain (B=-0.28, SE=0.11, p=.02), and had slower overall response time (B=-0.16, SE=0.07, p=.02). Relative to POMS, relapsing MOGAD participants were more accurate on the Executive Function domain (B = 0.70, SE=0.30, p=.02) and on the battery overall (B = 0.41, SE=0.18, p=.02). Relative to controls, overall PCNB score was significantly lower in the POMS group (B=-0.28, SE=0.06, p<.001) whereas the relapsing MOGAD participants did not differ from controls (p=.06) on the overall PCNB score. CONCLUSIONS: The relapsing MOGAD group demonstrated reduced reasoning skills and slower overall response time, relative to controls. A broad pattern of deficits was observed among POMS participants relative to controls. Overall, cognitive difficulties in the MOGAD group were milder relative to the POMS group.

Memory, processing of emotional stimuli, and volume of limbic structures in pediatric-onset multiple sclerosis.

OBJECTIVE: The limbic system is involved in memory and in processing of emotional stimuli. We measured volume of the hippocampus, amygdala, and thalamus, and assessed their relative contribution to episodic memory and emotion identification in POMS. METHOD: Sixty-five POMS participants (Mage = 18.3 ± 3.9 years; 48 female (73.8%)), average disease duration = 3.8 ± 3.8 years) and 76 age- and sex-matched controls (Mage = 18.1 ± 4.6 years; 49 female (64.5%)) completed the Penn Computerized Neurocognitive Battery (PCNB); 59 of 65 POMS participants and 69 out of 76 controls underwent 3 T MRI scanning. We derived age-adjusted Z-scores on accuracy and response time (RT) measures of episodic memory and emotion identification of the PCNB. Magnetic resonance imaging (MRI) volumetrics were normalized using the scaling factor computed by SIENAx. On PCNB tests that differed between groups, we used multiple linear regression to assess relationships between regional brain volumes and either episodic memory or emotion identification outcomes controlling for age, sex, accuracy/RT, and parental education. RESULTS: POMS participants were slower and less accurate than controls on the episodic memory domain but did not differ from controls on emotion outcomes. At the subtest level, POMS participants showed reduced accuracy on Word Memory (p = .002) and slower performance on Face Memory (p = .04) subtests. POMS participants had smaller total and regional brain volumes of the hippocampus, amygdala, and thalamus (p values ≤ 0.01). Collapsing across groups, both hippocampal and thalamic volume were significant predictors of Word Memory accuracy; hippocampal volume (B = 0.24, SE = 0.10, p = .02) was more strongly associated with Word Memory performance than thalamic volume (B = 0.16, SE = 0.05, p = .003), though the estimate with was less precise. CONCLUSIONS: POMS participants showed reduced episodic memory performance compared to controls. Aspects of episodic memory performance were associated with hippocampal and thalamic volume. Emotion identification was intact, despite volume loss in the amygdala.

Examining cognitive speed and accuracy dysfunction in youth and young adults with pediatric-onset multiple sclerosis using a computerized neurocognitive battery.

OBJECTIVE: We evaluated performance on the Penn Computerized Neurocognitive Battery (PCNB), a tool assessing accuracy and response time across four cognitive domains, alongside the Symbol Digit Modalities Test (SDMT), a measure of processing speed commonly used in MS. We determined whether performance decrements are more likely to be detected on measures of accuracy versus response time in pediatric-onset multiple sclerosis (POMS). METHODS: Performance on the SDMT, accuracy on PCNB tests belonging to four domains (executive function, episodic memory, complex cognition, social cognition), and response time on the PCNB were compared for 65 POMS patients (age range: 8-29 years) and 76 healthy controls (HCs) by ANCOVA. Associations between the Overall PCNB score and SDMT were examined for both groups, and their agreement in classifying impairment was assessed using Cohen's kappa. RESULTS: POMS patients (age at testing = 18.3 ± 4.0 years; age at POMS onset = 14.9 ± 2.3 years) demonstrated reduced accuracy relative to HCs on tests of working memory, attention/inhibition, verbal memory, and visuospatial processing, after adjusting for response time (p ≤ .002). Patients demonstrated slower overall response time on the PCNB (p = .003), while group differences on the SDMT did not meet significance (p = .03). Performance on the PCNB and SDMT were correlated (MS: r = 0.43, HC: r = 0.50, both p < .001), however, the degree of agreement for impairment was minimal (k = 0.22, p = .14). CONCLUSION: Specific cognitive deficits exist independently of slowed information processing speed in POMS, and may represent more significant areas of dysfunction. Delineation of accuracy and response time in neuropsychological assessment is important to identify areas of cognitive deficit in POMS. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Involvement of the Amygdala in Memory and Psychosocial Functioning in Pediatric-Onset Multiple Sclerosis.

Youth with multiple sclerosis (MS) often experience cognitive impairment and psychosocial disturbances. We describe the relationship between memory function, psychosocial skills, and brain volume in 32 patients with pediatric-onset MS and 30 controls. Amygdala volume was significantly lower in patients compared with controls. In general, poorer memory was associated with reduced functional communication skills and reduced amygdala volume. Greater amygdala volume in patients correlated with parent-reported functional communication and social skills. Adjusting for whole-brain volume, right amygdala volume was positively associated with visual memory; left amygdala volume was a stronger predictor of parent-reported social skills.

Informing pediatric rehabilitation: Language-based neuropsychological profile following traumatic brain injury and stroke secondary to arteriovenous malformation.

PURPOSE: To describe language-based neuropsychological outcomes following brain injury in two pediatric populations commonly treated in rehabilitation settings, namely severe traumatic brain injury (sTBI) and stroke secondary to arteriovenous malformation (AVM). METHODS: Investigated were children between the ages of 6 and 16 who were admitted to a brain injury rehabilitation program in a pediatric rehabilitation hospital and who were diagnosed with a left-sided sTBI (n= 16; mean age = 13.2) or a left-hemispheric stroke secondary to AVM (n= 16, mean age = 10.7). Groups were compared on demographic information, as well as general cognitive and language-based neuropsychological measures, controlling for age. RESULTS: Children in the AVM group presented with greater deficits, at trend levels, relative to the sTBI group on measures of working memory, verbal fluency, and an aphasia screening tool. CONCLUSIONS: This study represents an initial step in understanding the language-based neuropsychological outcomes of children diagnosed with sTBI compared to those with stroke secondary to AVM, which will help inform the rehabilitation process. With this knowledge, clinicians, families, and educators will be better equipped to provide informed individual rehabilitation programs, recommendations, and education for children and adolescents with brain injuries.

Using a dual-task protocol to investigate motor and cognitive performance in healthy children and youth.

OBJECTIVES: Mild traumatic brain injury (or concussion) is a prevalent yet understudied health concern in children and youth. This injury can cause dysfunction in both motor and cognitive domains; however, most literature focuses on single-task neuropsychological tests which only assess cognition. Although dual-task research on concussed children and youth is needed as many daily activities require both motor and cognitive domains, we must first investigate whether performing simultaneous motor and cognitive tasks of varied complexity impact these domains in healthy children and youth. PARTICIPANTS AND DESIGN: Data collected from 106 healthy children and youth (5-18 years) created a normative dataset. Participants performed motor (postural stability) and cognitive (visual attention) tasks under single- and dual-task conditions. The cognitive task difficulty remained constant while the motor task had four conditions of increasing difficulty. The relationship between the number of correct responses (cognitive performance) and sway index (motor performance) was determined using two repeated measures ANOVAs (p<0.05). RESULTS: Dual-task conditions resulted in reduced postural stability, with greater differences on the foam surface (F2,206=16.070, p<0.0005). No statistically significant differences were observed in attention (F4,101=0.713, p=0.584). CONCLUSIONS: Postural stability decreased under dual-task conditions, but attention was maintained or improved. Consequently, attention took precedence over postural control when performing tasks concurrently, demonstrating the ability for dual-task methodology to isolate specific processes. This study provides a normative dataset to be used during clinical management to identify functional deficits following concussion and acts as a starting point to explore dual-task protocols in children and youth following concussion.