Alessandra Erbetta

Cognitive Profiles and Visuoperceptual Abilities in Preterm and Term Spastic Diplegic Children With Periventricular Leukomalacia

Although relations between the extent of periventricular leukomalacia and neuropsychological performance in preterm children with spastic diplegia have been extensively investigated, studies on term children with spastic diplegia are rare. The authors examined 15 preterm children and 9 term children with spastic diplegia, all of whom had periventricular leukomalacia as a main magnetic resonance imaging (MRI) finding (excluding full-term spastic diplegic children with other MRI findings). Cognitive abilities (Griffith scale) and visuoperceptual abilities (Developmental Test of Visual Perception) were compared in the 2 groups and related to periventricular leukomalacia severity. Cognitive performance was substantially similar in the 2 groups. However, the overall Developmental Test of Visual Perception scores were below normal in the preterm and were normal in the term children; furthermore, visuoperceptual abilities were differentially affected in the preterm children, with visuomotor abilities more compromised than nonmotor visuoperceptual abilities. These children had similar cognitive performance and MRI findings, so the greater visuoperceptual compromise in the preterm group suggests a direct influence of prematurity, which may have adversely influenced the reorganization of visual centers and pathways following the initial developmental insult. The strabismus present in most preterm children would also have contributed to their greater visuoperceptual compromise. The authors conclude that the management of preterm and term children should differ, with concentration on visuoperceptual skills and rehabilitation in the former.

Basal Forebrain Involvement in Low-Functioning Autistic Children: A Voxel-Based Morphometry Study

BACKGROUND AND PURPOSE: Imaging studies have revealed brain abnormalities in the regions involved in functions impaired in ASD (social relations, verbal and nonverbal communication, and adaptive behavior). We performed a VBM whole-brain analysis to assess the areas involved in autistic children with DD. MATERIALS AND METHODS: Twenty-one developmentally delayed children with ASD (aged 3–10 years) were compared with 21 controls matched for age, sex, and sociocultural background. All ASD cases had been diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, with the Autism Diagnostic Observation Schedule-Generic, and the Autism Diagnostic Interview-Revised. The VBM data, covaried with intelligence quotient, age, and brain volume, were analyzed. RESULTS: ASD patients showed a pattern of regional GM reduction symmetrically affecting the basal forebrain, accumbens nucleus, cerebellar hemispheres, and perisylvian regions, including insula and putamen. Asymmetric involvement of GM was observed in other brain regions functionally connected to the basal forebrain, ie, an area located close to the medial and ventral surface of the frontal lobe. No regional WM differences were observed between the 2 groups. No significant differences between patients and controls were found regarding total brain volume, GM, and WM. CONCLUSIONS: In children with ASD and DD, the novel finding of our VBM study was the demonstration of reduced GM volume in the basal forebrain and the areas connected with it. This system is involved in social behavior, communication, and cognitive skills. Whether the involvement of the basal forebrain is characteristic of ASD or is related to the DD present in our patients needs further investigation.

Neoplastic meningitis from breast carcinoma with complete response to liposomal cytarabine: case report

Neoplastic meningitis from breast cancer often leads to a progressive neurologic deterioration followed by fatal outcome. The therapy is based on the administration of high dose systemic chemotherapy with drugs able to pass through the blood-brain barrier, such as methotrexate (MTX) and cytarabine, cranial or craniospinal irradiation, and intrathecal (IT) administration of MTX and/or cytarabine. However, these approaches only have modest efficacy and are associated with side effects for the patients. A depot formulation of liposomal cytarabine (DepoCyte®) has proven to be useful in clinical trials. We describe the case of a woman with a diagnosis of leptomeningeal carcinomatosis from breast carcinoma who presented cerebrospinal fluid normalization and prolonged complete MRI response to intrathecal chemotherapy with liposomal cytarabine (DepoCyte).

Cognition before and after chemotherapy alone in children with chiasmatic-hypothalamic tumors

Studies on adults with cancer, with or without CNS involvement, have shown that chemotherapy (CT) can affect cognitive functions. Two studies on children with optic pathway gliomas, involving the hypothalamus in some cases, and treated with CT according to various protocols reported the children maintaining a good IQ (no other cognitive abilities were tested). Among 18 children with chiasmatic-hypothalamic tumors (CHT) given front-line CT treatment at our institute using the same protocol (cisplatin and etoposide), we screened eight children for cognitive sequelae, correlating their test performance with several clinical variables (age at diagnosis and at time of treatment, time elapsing since treatment, and tumor volume reduction). The neuropsychological evaluation involved measuring IQ in all eight children and cognitive flexibility in three before CT (T1), then testing IQ, attention, memory and executive functions after CT (T2). The group as a whole showed no signs of any decline in IQ from T1 to T2, except for some WISC items, but IQ deteriorated severely in three patients with NF1 (only suspected in one case). At T2, the whole sample performed within normal range, except for two children showing a significantly worse result in two specific tests. The parents of the other 10 children, reported no substantial changes in their children’s behavior and intellectual vivacity in a semistructured telephone interview conducted in cooperation with the children’s teachers. CT alone as front-line treatment for CHT does not appear to have a negative effect on IQ and numerous neuropsychological tests. Some skills were more affected than others in our sample (albeit with a very low statistical significance of the impairment), and some patients seemed to be more vulnerable than others after CT. The multifactorial origin of such cognitive impairments is discussed. This type of study needs to be repeated in larger, but nonetheless carefully selected groups of patients.

Neuroimaging findings in 41 low-functioning children with autism spectrum disorder: A single-center experience

The data on the rate of brain imaging abnormalities in autistic spectrum disorders are still inconsistent. A recent study on patients with high-functioning autism found that approximately 90% of children had normal magnetic resonance imaging (MRI) scans whereas an unexpected high rate of MRI abnormalities was reported in 77 nonsyndromic autistic children with or without intellectual disability. The aim of this study was to evaluate the prevalence of neuroradiologic findings in low-functioning autistic children compared to controls matched for age. Minor brain abnormalities were found in 44% of patients and 22% of controls. Our main result is the high rate of mega cisterna magna in autistic patients. High rate of minor neuroradiologic abnormalities in low-functioning autistic patients could contribute to the research about the various endophenotypes and complete the clinical assessment of children with autistic spectrum disorder and intellectual disability.

Congenital Brain Damage: Cognitive Development Correlates With Lesion and Electroencephalographic Features

The purpose of this study was to assess cognitive development in 26 children with congenital focal brain lesion and unilateral spastic cerebral palsy first diagnosed and followed up for rehabilitation at our institution. Mean intelligence quotients (IQs) were correlated not only to the different features of the cerebral lesions, but also to the different types of electroencephalographic abnormalities. We also examined individual scores. We found that about 70% of the children had values of Full-Scale, Verbal, and Performance IQs within the normal range. No differences were found between left and right injured children. Different Verbal IQ–Performance IQ profiles were observed. Larger lesions and some electroencephalographic features, mainly signal slowing/attenuation as signs of structural brain damage, were significantly associated with lower intellectual abilities. The role of other factors, including genetic and environmental background variability, as well as rehabilitative treatments, on cognitive sequelae in such patients was discussed.

Verbal Dichotic Listening and Manual Performance in Children With Congenital Unilateral Brain Lesions

The authors assessed manual performance and verbal dichotic listening performance in 16 epilepsy-free children with congenital unilateral brain lesions and normal IQ to investigate cerebral reorganization. In all children, the paretic hand had fair grip function, but reaction times were impaired, and cerebral reorganization of hand function in those with right hemiplegia was shown by the high incidence of pathological left-handedness. The dichotic listening results showed that most children with left lesions had a left ear advantage significantly related to the extent of brain damage. This finding suggests that extent of cortical damage and presence of thalamic involvement, irrespective of neuropathology, are the primary factors inducing rightward cerebral language reorganization in children with unilateral congenital brain lesions.

Low-Functioning Autism and Nonsyndromic Intellectual Disability Magnetic Resonance Imaging (MRI) Findings

Previous neuroradiologic studies reported a high incidence of abnormalities in low-functioning autistic children. In this population, it is difficult to know which abnormality depends on autism itself and which is related to intellectual disability associated with autism. The aim of this study was to evaluate the frequency of neuroradiologic abnormalities in low-functioning autistic children compared to Intellectual Quotient and age-matched nonsyndromic children, using the same set of magnetic resonance imaging (MRI) sequences. MRI was rated as abnormal in 44% of autistic and 54% of children with intellectual disability. The main results were mega cisterna magna in autism and hypoplastic corpus callosum in intellectual disability. These abnormalities are morphologically visible signs of altered brain development. These findings, more frequent than expected, are not specific to the 2 conditions. Although MRI cannot be considered mandatory, it allows an in-depth clinical assessment in nonsyndromic intellectual-disabled and autistic children.

Hemispheric language organization after congenital left brain lesions: A comparison between functional transcranial Doppler and functional MRI

This study investigated whether functional transcranial Doppler ultrasound (fTCD) is a suitable tool for studying hemispheric lateralization of language in patients with pre-perinatal left hemisphere (LH) lesions and right hemiparesis. Eighteen left-hemisphere-damaged children and young adults and 18 healthy controls were assessed by fTCD and fMRI to evaluate hemispheric activation during two language tasks: a fTCD animation description task and a fMRI covert rhyme generation task. Lateralization indices (LIs), measured by the two methods, differed significantly between the two groups, for a clear LH dominance in healthy participants and a prevalent activation of right hemisphere in more than 80% of brain-damaged patients. Distribution of participants in terms of left, right, and bilateral lateralization was highly concordant between fTCD and fMRI values. Moreover, right hemisphere language dominance in patients with left hemispheric lesions was significantly associated with severity of cortical and subcortical damage in LH. This study suggests that fTCD is an easily applicable tool that might be a valid alternative to fMRI for large-scale studies of patients with congenital brain lesions.

Widespread Focal Cortical Alterations in Autism Spectrum Disorder with Intellectual Disability Detected by Threshold-Free Cluster Enhancement

BACKGROUND AND PURPOSE: In the past decades, a large body of work aimed at investigating brain structural anomalies accrued in autism spectrum disorder. Autism spectrum disorder is associated with intellectual disability in up to 50% of cases. However, only a few neuroimaging studies were conducted in autism spectrum disorder with intellectual disability, and none of them benefited from a nonsyndromic intellectual disability control group. MATERIALS AND METHODS: We performed a voxelwise investigation of the structural alterations in 25 children with autism spectrum disorder with intellectual disability by comparing them with 25 typically developing children and 25 nonsyndromic children with an intellectual disability. Besides a classic voxel-based morphometry statistical approach, the threshold-free cluster enhancement statistical approach was adopted. RESULTS: Classic voxel-based morphometry results did not survive family-wise error correction. The threshold-free cluster enhancement–based analysis corrected for family-wise error highlighted the following: 1) widespread focal cortical anomalies and corpus callosum alteration detected in autism spectrum disorder with intellectual disability; 2) basal ganglia and basal forebrain alteration detected both in autism spectrum disorder with intellectual disability and in nonsyndromic intellectual disability; and 3) differences in the frontocingulate-parietal cortex between autism spectrum disorder with intellectual disability and nonsyndromic intellectual disability. CONCLUSIONS: The present study suggests that the frontocingulate-parietal cortex may be the eligible key region for further investigations aiming at detecting imaging biomarkers in autism spectrum disorder with intellectual disability. The detection of structural alterations in neurodevelopmental disorders may be dramatically improved by using a threshold-free cluster enhancement statistical approach.