Neuropsychological functioning in children with early-treated phenylketonuria: impact of white matter abnormalities

Impact of white matter abnormalities (WMAs) on neuropsychological functioning in children with early-treated phenylketonuria (ETPKU) was examined. Children with ETPKU (20 males, 12 females, mean age 11 years 2 months, SD 3 years 6 months) and controls (20 males, 14 females, mean age 10 years 4 months, SD 3 years 1 month) aged 7 to 18 years were assessed using tests of attention, processing speed, memory and learning, executive function, and academic achievement. Those with ETPKU, exhibiting WMAs extending into subcortical/frontal regions (n=14), displayed significant impairments in a number of domains. Children with ETPKU but no WMAs (n=6), or pathology restricted to the posterior periventricular region (n=12), displayed only mild deficits. Concurrent phenylalanine levels correlated weakly with cognitive parameters, whereas lifetime phenylalanine levels were associated with deficits in several cognitive domains. Impairments in children with extensive WMAs are consistent with compromised neural transmission, which is characterized by dysmyelination. However, children with no detectable, or mild WMAs, also displayed cognitive problems, indicating that neuropsychological functioning in children with ETPKU is determined by a complex interaction of biological and environmental factors.     

Dementia Following Herpes Zoster Encephalitis

We studied the rare case of an older adult with dementia following herpes zoster encephalitis (HZE). This 71-year-old woman presented to us approximately 1 year following resolution of a rapid-onset episode of HZE, and subsequently underwent neuropsychological and neuroimaging examinations. Cognitive assessment revealed impairments in general cognitive functioning, verbal and nonverbal memory, executive functions, speed of information processing, attention/working memory, and motor skills. The patient's neuroimaging data, when compared to a demographically similar healthy control sample (n = 9), demonstrated moderate central and perisylvian brain volume loss, several subcortical lesions in the white matter, and resting state whole brain and hippocampal hypoperfusion. These findings highlight neuropsychological changes evident in a dementia syndrome of this type, and they suggest that early identification and treatment of HZE has implications for the preservation of long-term cognitive functioning.     

Cognitive functioning in orthostatic hypotension due to pure autonomic failure

Abstract Psychophysiological science proposes close interactions between cognitive processes and autonomic responses, yet the consequences of autonomic failure on cognitive functioning have not been documented. This pilot study investigates, for the first time, the cognitive profile of 14 patients with Pure Autonomic Failure (PAF). Each patient was administered a comprehensive battery of neuropsychological tests and neuroimaging investigation. A number of patients (n = 6) presented with cognitive impairment. The two most frequent types of impairment were: deficits of speed and attention, and executive functioning. Impairments of free recall memory, intellectual functioning, nominal and calculation functions were also documented, albeit in a much lower frequency. These cognitive changes were not always associated with white matter abnormalities. We speculate that the cognitive impairments associated with PAF represent consequences of systemic hypotension with cerebral underperfusion. However, a failure in integrated bodily arousal responses during cognitive behaviours may also contribute to some of the observed deficits.     

Cognitive visual dysfunctions in preterm children with periventricular leukomalacia

Aim  Cognitive visual dysfunctions (CVDs) reflect an impairment of the capacity to process visual information. The question of whether CVDs might be classifiable according to the nature and distribution of the underlying brain damage is an intriguing one in child neuropsychology.
Method  We studied 22 children born preterm (12 males, 10 females; mean age at examination 8y, range 6–15y; mean gestational age 30wks, range 28–36wks) with periventricular leukomalacia, spastic diplegia, normal intelligence (mean Full-scale IQ 84; mean Verbal IQ 97; mean Performance IQ 74), and normal visual acuity, focusing on higher visual functions. Brain magnetic resonance images (MRI) were analysed to establish the presence of lesions along the primary optic pathway, in the occipitoparietal and occipitotemporal regions.
Results  Most children displayed an uneven cognitive profile, with deficits in visual object recognition, visual imagery, visual–spatial skills, and visual memory, and sparing of visual associative abilities, non-verbal intelligence, and face and letter recognition. Conventional brain MRI did not document major alterations of parietal and temporal white matter, or cortical alteration of areas involved in visual associative functions.
Interpretation  We suggest a widespread involvement of higher visual processing systems, involving both the ventral and dorsal streams, in preterm children with periventricular leukomalacia. The lack of major alterations on conventional MRI does not exclude the possibility of malfunctioning of higher visual processing systems, expressing itself through discrete CVDs. Possible mechanisms underlying these neuropsychological deficits are discussed.     

Adults with Asperger syndrome with and without a cognitive profile associated with “non-verbal learning disability.” A brief report

Asperger syndrome (AS) and non-verbal learning disability (NLD) are both characterized by impairments in motor coordination, visuo-perceptual abilities, pragmatics and comprehension of language and social understanding. NLD is also defined as a learning disorder affecting functions in the right cerebral hemisphere. The present study investigates if individuals with AS and a cognitive profile consistent with NLD (i.e. verbal IQ > performance IQ) would also have other problems inherent in NLD, visual memory and attention, reading/writing ability and arithmetic in the presence of preserved verbal memory and attention. Forty-four individuals with AS were assessed with a battery of neuropsychological tests. Reading/writing and arithmetic abilities were investigated. Education and global social adaptive levels were studied. Very few AS participants, even though with NLD cognitive profile showed problems with any of the neurocognitive abilities or academic achievements. However, all had poor global social adaptive functioning and few had paid employment, regardless of their cognitive profile. The present study suggests that AS and NLD are two different conditions even though some individuals in both groups have the verbal IQ > performance IQ profile that has been proposed to be typical of both AS and NLD.     

Neuropsychological profile and social cognition in congenital central hypoventilation syndrome (CCHS): Correlation with neuroimaging in a clinical case

Introduction: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder due to paired-like homeobox gene (PHOX2B) mutations. CCHS patients suffer from dysregulation of the autonomic nervous system characterized by the absence of or extremely reduced response to hypercapnia and hypoxia, with neuropsychological deficits. The aim of this exploratory study is to describe the longitudinal neuropsychological profile and its correlations with magnetic resonance imaging (MRI) of a child with CCHS with a PHOX2B mutation. Method: A comprehensive neuropsychological evaluation was conducted serially at age 7 years 4 months and 10 years 3 months, including assessment of intellectual functioning (IQ), motor functioning, perception, attention, executive functions, language, memory, social cognition, academic skills, and psychopathology. Reliable change index (RCI) scores were used to assess changes between assessments. We collected spin lattice relaxation time (T1)-weighted, fluid-attenuated inversion recovery (FLAIR), and spin spin lattice relaxation time (T2)-weighted images from the child at age 10 years 3 months using a 1.5-tesla MRI scanner. Results: IQ, processing speed index (PSI), social cognition (theory of mind and facial emotion recognition), selective attention, naming, academic skills (reading/comprehension), and manual speed with right hand declined in the second evaluation relative to the initial evaluation, while visuoconstructional praxis, receptive vocabulary, working memory, and arithmetic skill improved. The patient showed a remarkable global deterioration in executive functions (planning, task flexibility, behavioral regulation, and metacognition) as revealed by parental report and clinical evaluation. MRI revealed gliosis from the head to tail of the hippocampus and thinning of parahippocampal gyri. Conclusions: In a clinical case of CCHS, serial evaluation revealed deterioration of executive functions and social cognition over a 3-year interval. These changes corresponded to hippocampal damage as revealed in MRI, which may have affected social cognition through its role in the default mode network. Serial neuropsychological assessment is clinically useful in managing the needs of these patients.     

Social skills and associated psychopathology in children with chromosome 22q11.2 deletion syndrome: implications for interventions

Background Although distinctive neuropsychological impairments have been delineated in children with chromosome 22q11 deletion syndrome (22q11DS), social skills and social cognition remain less well‐characterised. Objective To examine social skills and social cognition and their relationship with neuropsychological function/behaviour and psychiatric diagnoses in children with 22q11DS. Methods Sixty‐six children with 22q11DS and 54 control participants underwent neuropsychological testing and were administered the Diagnostic Analysis of Non‐Verbal Accuracy (DANVA) for face and auditory emotion recognition, a measure of social cognition: their parents/guardians were administered the Social Skills Rating System (SSRS) – parent version, Child Behavior Checklist (CBCL) – parent version and the Computerised Diagnostic Interview Schedule for Children (C‐DISC). Results The 22q11DS group exhibited significantly lower social skills total score and more problem social behaviours, lower neurocognitive functioning, higher rates of anxiety disorders and more internalising symptoms than the control group. Participants with 22q11DS also exhibited significant deficits in their ability to read facial expressions compared with the control group, but performed no differently than the control participants in the processing of emotions by tone of voice. Within the 22q11DS group, higher social competency was correlated with higher global assessment of functioning and parental socio‐economic status. Social competency was worse in those with anxiety disorders, attention deficit hyperactivity disorder, more than two psychiatric diagnoses on the C‐DISC and higher internalising symptoms. No significant correlations of SSRS scores were seen with IQ, executive functions, attention, or verbal learning and memory. No correlations were found between social cognition and social skill scores. Conclusion Our results indicate that social skills in children with 22q11DS are associated with behaviour/emotional functioning and not with neurocognition. Thus, treating the behaviour or emotional problems such as attention deficit hyperactivity disorder and anxiety disorders may provide a pathway for improving social skills in these children.     

A matched lesion analysis of childhood versus adult-onset brain injury due to unilateral stroke: another perspective on neural plasticity and recovery of social functioning.

BACKGROUND: The literature on neuroplasticity lacks a direct comparison of chronic neuropsychological and social outcomes following brain damage acquired in childhood versus adulthood, when lesions are matched across adults and children for size and location. METHODS: We paired adults and children with similar unilateral stroke lesions and then compared chronic neuropsychological and social outcomes. Quantitative comparisons were conducted, as well as qualitative analyses of each subject pair, focusing on specific domains of cognitive impairment and changes in social functioning. RESULTS: We found that learning and memory impairments were most common in both children and adults. Left hemisphere-lesioned children were normal on speech/language ratings, whereas their adult counterparts were borderline impaired. Impairments in social functioning were highly associated with hemispheric side of damage in adults, but not in children: Specifically, adults with right hemisphere lesions developed social defects much more frequently than adults with left hemisphere lesions, whereas this asymmetry was not evident in the children. Most importantly, though, was the overarching finding of a high degree of similarity between chronic neuropsychological and social function outcomes in adults and children with similarly located brain lesions due to unilateral stroke. CONCLUSIONS: On balance, the findings suggest that lesion location and size are prepotent factors determining neuropsychological and social recovery from stroke.     

Neuropsychological Profile in Children with Posterior Fossa Tumors with or Without Postoperative Cerebellar Mutism Syndrome (CMS)

Cerebellar mutism syndrome (CMS) is a common surgical sequela in children following posterior fossa tumor (PFT) resection. Here, we analyze the neuropsychological features associated with PFT in children, focusing particularly on the differential profiles associated with the presence or absence of CMS after surgery. We further examine the effect of post-resection treatments, tumor type, and presence/absence of hydrocephalus on surgical outcome. Thirty-six patients diagnosed with PFT (19 with and 17 without CMS) and 34 age- and gender-matched healthy controls (HCs) were recruited. A comprehensive neuropsychological evaluation was conducted in all patients postoperatively and in HCs, including an assessment of general cognitive ability, motor skills, perception, language, memory, attention, executive functions, and academic competence. CMS was found to be a clinical marker of lower neuropsychological profile scores across all cognitive domains except auditory-verbal processing and visual memory tasks. PFT patients not presenting CMS exhibited milder impairment in intellectual functioning, motor tasks, reasoning, language, verbal learning and recall, attention, cognitive executive functions, and academic competence. High-grade tumors were associated with slower processing speed and verbal delayed recall as well as alterations in selective and sustained attention. Hydrocephalus was detrimental to motor functioning and nonverbal reasoning. Patients who had undergone surgery, chemotherapy, and radiotherapy presented impaired processing speed, verbal learning, and reading. In addition to the deleterious effects of PFT, post-resection PFT treatments have a negative cognitive impact. These undesired consequences and the associated tumor-related damage can be assessed using standardized, long-term neuropsychological evaluation when planning rehabilitation.     

Attention lapses in children with spina bifida and hydrocephalus and children with attention-deficit/hyperactivity disorder

Attentional lapses are usually defined as temporary and often brief shifts of attention away from some primary task to unrelated internal information processing. This study addressed the incidence of attention lapses and differences in attentional functioning in 30 children with attention-deficit/hyperactivity disorder (ADHD), 26 healthy children, and 29 children with spina bifida myelomeningocele and hydrocephalus (SBH). Assessments were conducted using computerized tonic and phasic attention tests, the Symbol Digit Modalities Test (SDMT), and the Trail Making Test Form B (TMT–B). The group with SBH differed from normal controls on cognitive measures of attention and executive functions. The ADHD group obtained lower scores than the SBH group and healthy children. ANOVA results showed that there was an effect of shunt revisions and shunt-related infections on neuropsychological performance. Lapses of attention together with reaction time may thus represent important factors for the understanding of cognitive deficits in SBH.     

The association of MRI findings and neuropsychological functioning after the first recognized seizure

PURPOSE: To explore relationships between MRI abnormalities of the brain and neuropsychological functioning in children who were evaluated following their first recognized seizure. METHODS: Subjects were children aged 6 to 14 years with a first recognized seizure within the past 3 months who participated in a larger prospective study of child adaptation. The 249 children with neuropsychological testing and neuroimaging were studied. Children underwent neuropsychological examination an average of 2.8 months and MRI examination an average of 1.3 months after the first recognized seizure. On factor analysis four factors were found for neuropsychological function: LANG = Language, PS = Processing Speed, EC = Executive/ Construction, VMEM = Verbal Memory and Learning. For analysis, structural abnormalities found on MRI were classified as significant (yes/no) based on whether they were presumed to be related to the seizure condition. RESULTS: On MRI, 34 (14%) had structural abnormalities that were judged to be significant in that they were possibly related to their seizures. Children with significant abnormalities had significantly lower estimated IQ scores and significantly lower language, processing speed, executive/constructional ability, and verbal memory and learning factor scores than did children without significant abnormalities. CONCLUSIONS: Children who have structural brain abnormalities at onset have slightly lower cognitive functioning overall, and all neuropsychological domains seemed to be affected relatively equally. This pattern was apparent even when we restricted the analysis to children with intellectual functioning in the broadly normal range.     

Profiles and cognitive predictors of motor functions among early school-age children with mild intellectual disabilities

Background The purpose of the study was to describe sensorimotor profile in children with mild intellectual disability (ID), and to examine the association between cognitive and motor function. Methods A total of 233 children with mild ID aged 7 to 8 years were evaluated with measures of cognitive, motor and sensory integrative functioning. Results Children with mild ID performed significantly less well on all test measures. 44.2% of children scored in the impaired range on seven out of 22 sensorimotor measures. They had weaker fine motor skills than gross motor skills. Sensory integrative functions were only mildly impaired. Total IQ substantially predicted overall performance on each motor test. Specifically, verbal comprehension and processing speed indexes were significant predictors of gross and fine motor function. Conclusions Sensorimotor dysfunctions were found to be very frequent in children with mild ID. Early identification of sensorimtor impairments is essential to prompt early intervention and facilitate better integration into regular school settings.     

Neuropsychological Effect of Temporal Lobe Resection in Preadolescent Children with Epilepsy

Summary: Purpose : Numerous studies have demonstrated changes in cognitive, memory, and language functioning in adults and adolescents after temporal lobectomy, yet little information is available regarding neuropsychological outcome in preadolescent children.
Methods : We studied pre-and postoperative neuropsychological test results from 14 children who underwent temporal lobe resection for intractable epilepsy at age 7–12 years (mean 9.4 years).
Results : Thirteen patients (93%) had no seizures or less than one seizure a year at follow-up 23-48 months (mean 34 months) after operation. Postoperative neuropsychological testing was performed 6–9 months (mean 7 months) after surgery in 13 patients and 36 months after the first operation in 1 patient who underwent two-stage resection of a tumor. Verbal, Performance, and Full Scale IQ were initially in the low-average range, with no significant change across the pre-and postoperative evaluations. Immediate verbal memory performance decreased significantly in children who initially performed above the median preoperatively and tended to decrease in children who had left rather than right temporal lobe resection. Significant postoperative decreases in delayed memory scores were independent of preoperative ability or side of resection.
Conclusions : Our small study suggests vulnerability to postoperative decline in immediate verbal memory scores in preadolescent children who have higher baseline immediate memory function or undergo left rather than right temporal lobe resection, similar to that observed in adolescents in adults. The entire group exhibited a statistically significant decrease in delayed verbal memory. Study of larger series of patients will be important to clarify further the short-and long-term risks and benefits of temporal lobe resection in childhood.     

Cognitive outcome of parietooccipital resection in children with epilepsy

Purpose: We followed the neuropsychological development of five children who underwent unilateral neurosurgery of the occipitoparietal lobes as a treatment for epilepsy caused by a developmental lesion (cortical dysplasia). Methods: The follow‐up period ranged from 3–7 years postsurgery. Results: Two participants had a verbal intelligence quotient (IQ) >100 and three had a verbal IQ between 65 and 80. All five children had abnormal nonverbal IQ and exhibited deficits related to visual attention, object recognition, and praxis. Nevertheless, our results suggest that brain plasticity after parietooccipital epilepsy surgery in young children allows for a schooling level of cognitive skills such as reading and arithmetic. Discussion: Although recovery for visual perceptual cognition was more limited than for verbal functions, long‐term neuropsychological outcomes showed that early surgery for epilepsy offers the possibility of optimizing cognitive outcomes in children with posterior intractable epilepsies.     

Selective neuropsychological impairments and related clinical factors in children with moyamoya disease of the transient ischemic attack type

Purpose

Moyamoya disease is characterized by progressive narrowing of bilateral internal carotid arteries. Neuropsychological impairments are suspected due to frequent involvement of the frontotemporal areas. The present study thus aimed to investigate the pattern of neuropsychological function in children diagnosed with moyamoya disease.

Methods

Thirteen children with moyamoya disease of the transient ischemic attack type received standardized neuropsychological tests that evaluate general intellectual function, verbal comprehension, perceptual organization, working memory, processing speed, episodic memory, category fluency and visuospatial function. Related clinical factors were also analyzed.

Results

The results showed single-domain cognitive impairment in around 15 % of patients and multiple-domain cognitive impairments in 23 % of patients. Selective impairments of episodic memory and processing speed were especially noted in those with younger age of onset and prolonged symptom duration.

Conclusions

Neuropsychological impairments are not infrequent in children with moyamoya disease despite normal general intellectual functioning. The pattern of cognitive dysfunction is often associated with lesions in frontotemporal areas. Early detection and intervention shall be considered regarding cognitive outcome in pediatric group.     

Schizotypal disorder and schizophrenia: a profile analysis of neuropsychological functioning in Japanese patients.

This study compares neuropsychological functioning in a Japanese schizophrenia spectrum disorder group and a group of healthy Japanese volunteers. Participants were 37 patients diagnosed with schizophrenia, 28 schizotypal patients, and 99 psychiatrically-normal volunteers. A wide range of cognitive measures were examined. All participants completed a Japanese version of a neuropsychological battery assessing executive function, working memory, processing speed, language, verbal memory, and spatial organization. Comparisons of neuropsychological function demonstrated similarities and differences between patients diagnosed with schizotypal disorder and those diagnosed with schizophrenia. Impairments in verbal memory, language, and processing speed were common to both patient groups and may represent a vulnerability to schizophrenia. Impairments in aspects of working memory, spatial organization and executive function were preferentially observed in schizophrenia and may be features of the overt manifestation of psychosis. Possible differences in the contributions of prefrontal and temporo-limbic structures provide direction for further studies.     

Local processing and social skills in children with Autism Spectrum Disorders: The role of anxiety and cognitive functioning

The present study examined the relations between anxiety, cognitive functioning, local processing, and social skills in a group of 102 children diagnosed with an Autism Spectrum Disorder. The results indicated that children diagnosed with Asperger's Disorder had significantly higher cognitive functioning and enhanced local processing (i.e., Block Design scores) compared to those diagnosed with Autistic Disorder or PDD-NOS. Regression analyses results showed that anxiety and cognitive functioning moderated the association between local processing and social skills. For children with low cognitive functioning and high anxiety, greater local processing was associated with poorer social skills than those with high cognitive functioning, high anxiety, and greater local processing. For children with high cognitive functioning and high anxiety, enhanced local processing was associated with better social skills than those with high cognitive functioning and reduced local processing. Implications of these findings are discussed.     

Impairment of executive cognitive functioning in males with fragile X-associated tremor/ataxia syndrome.

The fragile X-associated tremor/ataxia syndrome (FXTAS) is a recently identified phenotype associated with trinucleotide repeat expansions in the premutation range of the fragile X mental retardation 1 (FMR1) gene. In addition to progressive gait ataxia, action tremor, peripheral neuropathy, and parkinsonism, FXTAS involves impaired cognition. Our preliminary research suggests that executive cognitive functioning (ECF) is especially affected. In this study, a brief neuropsychological exam was administered to 33 men with FXTAS and 27 healthy controls. Compared with controls, individuals with FXTAS showed statistically significant impairments on measures from the Wechsler Adult Intelligence Scale, third edition (WAIS-III; verbal IQ, performance [nonverbal] IQ, verbal comprehension, perceptual organization, and processing speed). FXTAS subjects scored significantly lower on three of four measures of ECF and on two tests of information processing speed. The results provide evidence that FXTAS involves impairment of general intellectual functioning, with marked impairment of executive cognitive abilities. The pattern of cognitive performance is somewhat similar to that observed in the frontal variant of frontotemporal dementia and several of the spinocerebellar ataxias, but differs from the deficits observed in dementia of the Alzheimer type.     

Cognitive skills in children with intractable epilepsy: comparison of surgical and nonsurgical candidates

PURPOSE: To compare neuropsychological performance of two groups of children with intractable epilepsy: those who are surgical candidates, and those who are not. METHODS: Intelligence, verbal memory, visual memory, academic skills, and sustained attention were measured in children aged 6-18 years. The effects of number of antiepileptic drugs (AEDs), seizure frequency, age at seizure onset, and duration of seizure disorder were examined. RESULTS: Both groups had high rates of impairment. Group differences were found only on the verbal memory task. Children who experienced seizures in clusters had higher IQ, reading comprehension, and arithmetic scores. Age at seizure onset and proportion of life with seizures were related to IQ. Performance did not vary with AED monotherapy versus polytherapy. CONCLUSIONS: Few differences exist in cognitive performance between children with intractable seizures who are and those who are not surgical candidates. These findings suggest that children who are not surgical candidates can serve as good controls in studies on cognitive outcome of surgery.     

Preserved episodic memory in subcortical band heterotopia

PURPOSE: Neuropsychological profiles of four patients with subcortical band heterotopia (SBH) are presented to delineate further the phenotype of this disorder. METHODS: Standardized, norm-referenced measures of cognitive functioning, including intelligence, processing speed, attention, language, visuomotor skills, memory, and fine motor ability were administered to four patients with magnetic resonance imaging evidence of SBH. RESULTS: Despite intellectual impairment and other severe cognitive deficits, all four patients displayed relatively intact episodic memory. CONCLUSIONS: This selective sparing of memory functions has not been previously reported in individuals with SBH and suggests that doublecortin does not play a role in the development of memory systems in the mesial temporal region, which tend to be spared in SBH.