Early clinical and MRI biomarkers of cognitive and motor outcomes in very preterm born infants.

BACKGROUND: This study aimed to identify which MRI and clinical assessments, alone or in combination, from (i) early (32 weeks postmenstrual age, PMA), (ii) term equivalent age (TEA) and (iii) 3 months corrected age (CA) are associated with motor or cognitive outcomes at 2 years CA in infants born <31 weeks gestation. METHODS: Prospective cohort study of 98 infants who underwent early and TEA MRI (n = 59 males; median birth gestational age 28 + 5 weeks). Hammersmith Neonatal Neurological Examination (HNNE), NICU Neonatal Neurobehavioural Scale and General Movements Assessment (GMs) were performed early and at TEA. Premie-Neuro was performed early and GMs, Test of Infant Motor Performance and visual assessment were performed at TEA and 3 months CA. Neurodevelopmental outcomes were determined using Bayley Scales of Infant and Toddler Development 3rd edition. RESULTS: The best combined motor outcome model included 3-month GMs (ß = -11.41; 95% CI = -17.34, -5.49), TEA MRI deep grey matter score (ß = -6.23; 95% CI = -9.47, -2.99) and early HNNE reflexes (ß = 3.51; 95% CI = 0.86, 6.16). Combined cognitive model included 3-month GMs (ß = -10.01; 95% CI = -15.90, -4.12) and TEA HNNE score (ß = 1.33; 95% CI = 0.57, 2.08). CONCLUSION: Early neonatal neurological assessment improves associations with motor outcomes when combined with term MRI and 3-month GMs. Term neurological assessment combined with 3-month GMs improves associations with cognitive outcomes. IMPACT: We present associations between 32- and 40-week MRI, comprehensive clinical assessments and later 2-year motor and cognitive outcomes for children born <31 weeks gestation. MRI and clinical assessment of motor, neurological and neurobehavioural function earlier than term equivalent age in very preterm infants is safe and becoming more available in clinical settings. Most of these children are discharged from hospital before term age and so completing assessments prior to discharge can assist with follow up. MRI and neurological assessment prior to term equivalent age while the child is still in hospital can provide earlier identification of children at highest risk of adverse outcomes and guide follow-up screening and intervention services.

Understanding the impact of bilateral brain injury in children with unilateral cerebral palsy.

The presence of bilateral brain injury in patients with unilateral cerebral palsy (CP) may impact neuroplasticity in the ipsilateral hemisphere; however, this pattern of injury is typically under-analyzed due to the lack of methods robust to severe injury. In this study, injury-robust methods have been applied to structural brain magnetic resonance imaging (MRI) data of a cohort of 91 children with unilateral CP (37 with unilateral and 54 with bilateral brain injury, 4-17 years) and 44 typically developing controls (5-17 years), to determine how brain structure is associated with concurrent motor function, and if these associations differ between patients with unilateral or bilateral injury. Regression models were used to associate these measures with two clinical scores of hand function, with patient age, gender, brain injury laterality, and interaction effects included. Significant associations with brain structure and motor function were observed (Pearson's r = .494-.716), implicating several regions of the motor pathway, and demonstrating an accurate prediction of hand function from MRI, regardless of the extent of brain injury. Reduced brain volumes were observed in patients with bilateral injury, including volumes of the thalamus and corpus callosum splenium, compared to those with unilateral injury, and the healthy controls. Increases in cortical thickness in several cortical regions were observed in cohorts with unilateral and bilateral injury compared to controls, potentially suggesting neuroplasticity might be occurring in the inferior frontal gyrus and the precuneus. These findings identify prospective useful target regions for transcranial magnetic stimulation intervention.

Transcranial Direct Current Stimulation (tDCS) in Unilateral Cerebral Palsy: A Pilot Study of Motor Effect.

Transcranial Direct Current Stimulation (tDCS) is an emerging tool to improve upper limb motor functions after stroke acquired in adulthood; however, there is a paucity of reports on its efficacy for upper limb motor rehabilitation in congenital or early-acquired stroke. In this pilot study we have explored, for the first time, the immediate effects, and their short-term persistence, of a single application of anodal tDCS on chronic upper limb motor disorders in children and young individuals with Unilateral Cerebral Palsy (UCP). To this aim, in a crossover sham-controlled study, eight subjects aged 10-28 years with UCP underwent two sessions of active and sham tDCS. Anodal tDCS (1.5 mA, 20 min) was delivered over the primary motor cortex (M1) of the ipsilesional hemisphere. Results showed, only following the active stimulation, an immediate improvement in unimanual gross motor dexterity of hemiplegic, but not of nonhemiplegic, hand in Box and Block test (BBT). Such improvement remained stable for at least 90 minutes. Performance of both hands in Hand Grip Strength test was not modified by anodal tDCS. Improvement in BBT was unrelated to participants' age or lesion size, as revealed by MRI data analysis. No serious adverse effects occurred after tDCS; some mild and transient side effects (e.g., headache, tingling, and itchiness) were reported in a limited number of cases. This study provides an innovative contribution to scientific literature on the efficacy and safety of anodal tDCS in UCP. This trial is registered with NCT03137940.

Potentials of Ultrahigh-Field MRI for the Study of Somatosensory Reorganization in Congenital Hemiplegia.

Reorganization of somatosensory function influences the clinical recovery of subjects with congenital unilateral brain lesions. Ultrahigh-field (UHF) functional MRI (fMRI) with the use of a 7 T magnet has the potential to contribute fundamentally to the current knowledge of such plasticity mechanisms. The purpose of this study was to obtain preliminary information on the possible advantages of the study of somatosensory reorganization at UHF fMRI. We enrolled 6 young adults (mean age 25 ± 6 years) with congenital unilateral brain lesions (4 in the left hemisphere and 2 in the right hemisphere; 4 with perilesional motor reorganization and 2 with contralesional motor reorganization) and 7 healthy age-matched controls. Nondominant hand sensory assessment included stereognosis and 2-point discrimination. Task-dependent fMRI was performed to elicit a somatosensory activation by using a safe and quantitative device developed ad hoc to deliver a reproducible gentle tactile stimulus to the distal phalanx of thumb and index fingers. Group analysis was performed in the control group. Individual analyses in the native space were performed with data of hemiplegic subjects. The gentle tactile stimulus showed great accuracy in determining somatosensory cortex activation. Single-subject gentle tactile stimulus showed an S1 activation in the postcentral gyrus and an S2 activation in the inferior parietal insular cortex. A correlation emerged between an index of S1 reorganization (distance between expected and reorganized S1) and sensory deficit (p < 0.05) in subjects with hemiplegia, with higher distance related to a more severe sensory deficit. Increase in spatial resolution at 7 T allows a better localization of reorganized tactile function validated by its correlation with clinical measures. Our results support the S1 early-determination hypothesis and support the central role of topography of reorganized S1 compared to a less relevant S1-M1 integration.

Alterations in regional shape on ipsilateral and contralateral cortex contrast in children with unilateral cerebral palsy and are predictive of multiple outcomes.

Congenital brain lesions result in a wide range of cerebral tissue alterations observed in children with cerebral palsy (CP) that are associated with a range of functional impairments. The relationship between injury severity and functional outcomes, however, remains poorly understood. This research investigates the differences in cortical shape between children with congenital brain lesions and typically developing children (TDC) and investigates the correlations between cortical shape and functional outcome in a large cohort of patients diagnosed with unilateral CP. Using 139 structural magnetic resonance images, including 95 patients with clinically diagnosed CP and 44 TDC, cortical segmentations were obtained using a modified expectation maximization algorithm. Three shape characteristics (cortical thickness, curvature, and sulcal depth) were computed within a number of cortical regions. Significant differences in these shape measures compared to the TDC were observed on both the injured hemisphere of children with CP (P < 0.004), as well as on the apparently uninjured hemisphere, illustrating potential compensatory mechanisms in these children. Furthermore, these shape measures were significantly correlated with several functional outcomes, including motor, cognition, vision, and communication (P < 0.012), with three out of these four models performing well on test set validation. This study highlights that cortical neuroplastic effects may be quantified using MR imaging, allowing morphological changes to be studied longitudinally, including any influence of treatment. Ultimately, such approaches could be used for the long term prediction of outcomes and the tailoring of treatment to individuals. Hum Brain Mapp 37:3588-3603, 2016. © 2016 Wiley Periodicals, Inc.

Optimization of MRI-based scoring scales of brain injury severity in children with unilateral cerebral palsy.

BACKGROUND: Several scoring systems for measuring brain injury severity have been developed to standardize the classification of MRI results, which allows for the prediction of functional outcomes to help plan effective interventions for children with cerebral palsy. OBJECTIVE: The aim of this study is to use statistical techniques to optimize the clinical utility of a recently proposed template-based scoring method by weighting individual anatomical scores of injury, while maintaining its simplicity by retaining only a subset of scored anatomical regions. MATERIALS AND METHODS: Seventy-six children with unilateral cerebral palsy were evaluated in terms of upper limb motor function using the Assisting Hand Assessment measure and injuries visible on MRI using a semiquantitative approach. This cohort included 52 children with periventricular white matter injury and 24 with cortical and deep gray matter injuries. A subset of the template-derived cerebral regions was selected using a data-driven region selection algorithm. Linear regression was performed using this subset, with interaction effects excluded. RESULTS: Linear regression improved multiple correlations between MRI-based and Assisting Hand Assessment scores for both periventricular white matter (R squared increased to 0.45 from 0, P < 0.0001) and cortical and deep gray matter (0.84 from 0.44, P < 0.0001) cohorts. In both cohorts, the data-driven approach retained fewer than 8 of the 40 template-derived anatomical regions. CONCLUSION: The equal or better prediction of the clinically meaningful Assisting Hand Assessment measure using fewer anatomical regions highlights the potential of these developments to enable enhanced quantification of injury and prediction of patient motor outcome, while maintaining the clinical expediency of the scoring approach.

Serum cortisol concentrations during induced hypothermia for perinatal asphyxia are associated with neurological outcome in human infants.

Birth asphyxia is a cause of neonatal death or adverse neurological sequelae. Biomarkers can be useful to clinicians in order to optimize intensive care management and communication of prognosis to parents. During perinatal adverse events, increased cortisol secretion is due to hypothalamo-pituitary-adrenal axis activation. We aimed to investigate if cortisol variations during therapeutic hypothermia are associated with neurodevelopmental outcome. We compared 18 cases (neonates with birth asphyxia) with 18 controls (healthy term newborns) and confirmed increased serum cortisol concentrations following the peri-partum adverse event. Among cases, we stratified patients according to neurological outcome at 18 months (group A - good; group B - adverse) and found that after 24 h of therapeutic hypothermia serum cortisol concentration was significantly lower in group A vs group B (28.7 ng/mL vs 344 ng/mL, *p = 0.01). In group B serum, cortisol concentration decreased more gradually during therapeutic hypothermia. We conclude that monitoring serum cortisol concentration during neonatal therapeutic hypothermia can add information to clinical evaluation of neonates with birth asphyxia; cortisol values after the first 24 h of hypothermia can be a biomarker associated with neurodevelopmental outcome at 18 months of age.

Mitii™ ABI: study protocol of a randomised controlled trial of a web-based multi-modal training program for children and adolescents with an Acquired Brain Injury (ABI).

BACKGROUND: Acquired brain injury (ABI) refers to multiple disabilities arising from damage to the brain acquired after birth. Children with an ABI may experience physical, cognitive, social and emotional-behavioural impairments which can impact their ability to participate in activities of daily living (ADL). Recent developments in technology have led to the emergence of internet-delivered therapy programs. "Move it to improve it" (Mitii™) is a web-based multi-modal therapy that comprises upper limb (UL) and cognitive training within the context of meaningful physical activity. The proposed study aims to compare the efficacy of Mitii™ to usual care to improve ADL motor and processing skills, gross motor capacity, UL and executive functioning in a randomised waitlist controlled trial. METHODS/DESIGN: Sixty independently ambulant children (30 in each group) at least 12 months post ABI will be recruited to participate in this trial. Children will be matched in pairs at baseline and randomly allocated to receive either 20 weeks of Mitii™ training (30 min per day, six days a week, with a potential total dose of 60 h) immediately, or be waitlisted for 20 weeks. Outcomes will be assessed at baseline, immediately post-intervention and at 20 weeks post-intervention. The primary outcomes will be the Assessment of Motor and Process Skills and 30 s repetition maximum of functional strength exercises (sit-to-stand, step-ups and half kneel to stand). Measures of body structure and functions, activity, participation and quality of life will assess the efficacy of Mitii™ across all domains of the International Classification of Functioning, Disability and Health framework. A subset of children will undertake three tesla (3T) magnetic resonance imaging scans to evaluate functional neurovascular changes, structural imaging, diffusion imaging and resting state functional connectivity before and after intervention. DISCUSSION: Mitii™ provides an alternative approach to deliver intensive therapy for children with an ABI in the convenience of the home environment. If Mitii™ is found to be effective, it may offer an accessible and inexpensive intervention option to increase therapy dose. TRIAL REGISTRATION: ANZCTR12613000403730.

Cognitive strategies for locomotor navigation in normal development and cerebral palsy.

Visual-spatial impairment is a fundamental disorder in cerebral palsy (CP). However, current spatial testing is restricted to reaching space, whereas navigational space is seldom assessed. The Magic Carpet test, derived from the Corsi Block-tapping Task (CBT) for visual-spatial memory, is a new developmental test for navigation. The performances of the Magic Carpet test and CBT were assessed in 17 children with unilateral and bilateral spastic CP. The results were compared with an equal number of typically developing children, matched for age and sex. Magnetic resonance imaging scans of children with CP were scored according to a newly validated semi-quantitative classification. CBT span was significantly lower in CP, especially in bilateral forms, than in the comparison group, whereas the Magic Carpet test span did not significantly differ between the groups. CBT span, but not the Magic Carpet span, was related to gestational age at birth and to basic visual function. Both the CBT span and the Magic Carpet test were related to overall right-hemispheric impairment. In addition, CBT correlated with right periventricular impairment. In CP, navigation is differently impaired than visual spatial memory, and less tightly related to preterm birth, basic visual function, and deep white matter injury. The exploration of navigational space could prove useful in enhancing spatial representation and reference-frame manipulation in CP.

Is one motor cortex enough for two hands?

We report on a patient with mirror movements sustained by a mono-hemispheric fast control of bilateral hand muscles and normal hand function. Transcranial magnetic stimulation of the right motor cortex evoked contractions of muscles in both hands while no responses were observed from the left hemisphere. Somatosensory-evoked potentials, functional magnetic resonance, and diffusion tractography showed evidence of sensorimotor dissociation and asymmetry of corticospinal projections, suggestive of reorganization after early unilateral left brain lesion. This is the first evidence that, in certain rare conditions, good hand function is possible with ipsilateral corticospinal reorganization, supporting the role of unexplored mechanisms of motor recovery.

Altered corticomotor-cerebellar integrity in young ataxia telangiectasia patients.

Magnetic resonance imaging (MRI) research in identifying altered brain structure and function in ataxia-telangiectasia, an autosomal recessive neurodegenerative disorder, is limited. Diffusion-weighted MRI were obtained from 11 ataxia telangiectasia patients (age range, 7-22 years; mean, 12 years) and 11 typically developing age-matched participants (age range, 8-23 years; mean, 13 years). Gray matter volume alterations in patients were compared with those of healthy controls using voxel-based morphometry, whereas tract-based spatial statistics was employed to elucidate white matter microstructure differences between groups. White matter microstructure was probed using quantitative fractional anisotropy and mean diffusivity measures. Reduced gray matter volume in both cerebellar hemispheres and in the precentral-postcentral gyrus in the left cerebral hemisphere was observed in ataxia telangiectasia patients compared with controls (P < 0.05, corrected for multiple comparisons). A significant reduction in fractional anisotropy in the cerebellar hemispheres, anterior/posterior horns of the medulla, cerebral peduncles, and internal capsule white matter, particularly in the left posterior limb of the internal capsule and corona radiata in the left cerebral hemisphere, was observed in patients compared with controls (P < 0.05). Mean diffusivity differences were observed within the left cerebellar hemisphere and the white matter of the superior lobule of the right cerebellar hemisphere (P < 0.05). Cerebellum-localized gray matter changes are seen in young ataxia telangiectasia patients along with white matter tract degeneration projecting from the cerebellum into corticomotor regions. The lack of cortical involvement may reflect early-stage white matter motor pathway degeneration within young patients.

Quantitative comparison of cortical and deep grey matter in pathological subtypes of unilateral cerebral palsy.

AIM: The aim of this study was to quantify grey matter changes in children with unilateral cerebral palsy (UCP), differentiating between cortical or deep grey matter (CDGM) lesions, periventricular white matter (PWM) lesions, and unilateral and bilateral lesions. METHOD: In a cross-sectional study we obtained high resolution structural magnetic resonance images from 72 children (41 males, 31 females, mean age 10y 9mo [SD 3y 1mo], range 5y 1mo-17y 1mo) with UCP (33 left, 39 right hemiplegia; Manual Ability Classification System level I n=29, II n=43; Gross Motor Function Classification System level I n=46, II n=26), and 19 children with typical development (CTD; eight males, 11 females, mean age 11y 2mo [SD 2y 7mo], range 7y 8mo-16y 4mo). Images were classified by lesion type and analyzed using voxel-based morphometry (VBM) and subcortical volumetric analysis. RESULTS: Deep grey matter volumes were not significantly different between children with CDGM and PWM lesions, with the thalamus, putamen, and globus pallidus being reduced unilaterally in both groups compared with CTD (p≤0.001). Children with CDGM lesions additionally showed widespread cortical changes involving all lobes using VBM (p<0.01). Children with bilateral lesions had reduced thalamus and putamen volumes bilaterally (p<0.001). The thalamic volume was reduced bilaterally in children with unilateral lesions (p=0.004). INTERPRETATION: Lesions to the PWM cause secondary changes to the deep grey matter structures similar to primary changes seen in CDGM lesions. Despite having a unilateral phenotype, grey matter changes are observed bilaterally, even in children with unilateral lesions.

Reliability of a novel, semi-quantitative scale for classification of structural brain magnetic resonance imaging in children with cerebral palsy.

AIM: To describe the development of a novel rating scale for classification of brain structural magnetic resonance imaging (MRI) in children with cerebral palsy (CP) and to assess its interrater and intrarater reliability. METHOD: The scale consists of three sections. Section 1 contains descriptive information about the patient and MRI. Section 2 contains the graphical template of brain hemispheres onto which the lesion is transposed. Section 3 contains the scoring system for the quantitative analysis of the lesion characteristics, grouped into different global scores and subscores that assess separately side, regions, and depth. A larger interrater and intrarater reliability study was performed in 34 children with CP (22 males, 12 females; mean age at scan of 9 y 5 mo [SD 3 y 3 mo], range 4 y-16 y 11 mo; Gross Motor Function Classification System level I, [n=22], II [n=10], and level III [n=2]). RESULTS: Very high interrater and intrarater reliability of the total score was found with indices above 0.87. Reliability coefficients of the lobar and hemispheric subscores ranged between 0.53 and 0.95. Global scores for hemispheres, basal ganglia, brain stem, and corpus callosum showed reliability coefficients above 0.65. INTERPRETATION: This study presents the first visual, semi-quantitative scale for classification of brain structural MRI in children with CP. The high degree of reliability of the scale supports its potential application for investigating the relationship between brain structure and function and examining treatment response according to brain lesion severity in children with CP.

Long-term outcomes of congenital cytomegalovirus infection in children early identified by extended hearing-targeted screening.

OBJECTIVES: Congenital Cytomegalovirus (cCMV) has been associated with hearing, vision, and neurodevelopmental long-term sequelae. Despite the social burden associated with the disease, a universally accepted consensus on screening, diagnostic, therapeutic and follow-up approaches has not been reached. The present observational retrospective study aims at describing long-term sequelae and radiological abnormalities associated with cCMV in children early identified by extended hearing-targeted screening and evaluated by audiological follow-up in a single III Level Audiological Referral Center for at least 2 years. METHODS: Audiological neonatal and follow-up data were available for all subjects. Data collection included clinical neonatal and virological assessment at birth. Ophthalmological, neurodevelopmental and neuroradiological follow-up abnormalities compatible with cCMV sequelae were collected by clinical reports. Spearman's rank correlation coefficient (rho-ρ) was used to evaluate possible correlations among the considered parameters. RESULTS: 61 newborns were identified by extended hearing-targeted cCMV screening and diagnosed mostly (83.6 %) by PCR viral DNA extraction in urine collected within the 15° day of life. Seventeen babies were born preterm, with a mean gestational age of 33.5 weeks. Sixteen patients (26.2 %) were admitted to an Intensive or sub-Intensive Neonatal Care Unit. At birth, 35 newborns were symptomatic (57.3 %), and 19 of them received antiviral treatment by valganciclovir or ganciclovir. Overall, 20 children (32.7 %) were diagnosed with sensorineural hearing loss (SNHL), among them 17 (85 %) were refer at the newborn hearing screening while 3 (15 %) were Pass. 5/20 children (25 %) presented isolated SNHL, while in 15/20 (75 %) children SNHL was associated to other long-term sequelae. In 5 patients (25 %) a progression of the hearing threshold was observed, with a mean age of progression of 26 months of age. Risk factors for progression were a worse final hearing threshold (Spearman's ρ = 0.434; p = 0.0001) and a worse hearing threshold at birth (Spearman's ρ = 0.298; p = 0.020). Thirteen children were fitted with hearing aids, 8 of whom subsequently underwent cochlear implantation. Concerning long term impairments, 10/61 children (17 %) presented a variety of ophthalmological sequelae, while 16/40 cCMV patients (40 %) were diagnosed with neurodevelopmental abnormalities. Language delays were significantly associated with a worse hearing threshold (ρ = 0.582; p = 0.0001) and with other neurocognitive abnormalities (ρ = 0.677, p = 0.0001). 30 children underwent radiological brain evaluation by Magnetic Resonance Imaging, and 63.3 % of them presented abnormalities compatible with cCMV. Mean viral load at birth did not show significant associations with long-term sequelae. CONCLUSIONS: The study highlights the diverse and significant long-term sequelae of cCMV infection detected through early screening. With a significant proportion of cCMV children developing sensorineural hearing loss, ophthalmological and neurodevelopmental issues, the results emphasize the importance of continuous, multidisciplinary follow-up. Early identification and tailored interventions are crucial for improving the long-term health and quality of life of children affected by cCMV.

Longitudinal assessment of brain lesions in children with cerebral palsy and association with motor functioning.

BACKGROUND: The semi-quantitative scale of structural brain Magnetic Resonance Imaging (sqMRI) is a valid and reliable measure of brain lesion extent in children with cerebral palsy (CP) >3-years. This system scores lesion burden for each major brain region. The sum of the scores gives a global score ranging from 0 to 48. PURPOSE: To investigate how sqMRI scores changed from infancy to school-age, and whether these were associated with lesion load, age at first assessment, and gross motor function and its changes. MATERIALS AND METHODS: Twenty-eight children with CP underwent MRI and motor (Gross Motor Function Measure-66; GMFM-66) assessments when <40-months and again when 8-12-years. We investigated whether (i) toddler/preschool-age sqMRI scores (Time 1) reflected school-age sqMRI scores (Time 2); (ii) temporal changes in sqMRI scores (Time 1-Time 2 difference) were related to the child's age at Time 1 and lesion extent; (iii) early or later sqMRI scores were associated with motor functioning; (iv) sqMRI scores' longitudinal changes were associated with motor changes. RESULTS: Except for the corticosubcortical (grey-matter only) layers, sqMRI scores were significantly higher ('higher lesion load') at Time 1 than at Time 2. Age at Time 1 was not associated with temporal changes in global sqMRI scores. Higher lesion load at Time 2, but not at Time 1, was associated with smaller temporal changes in the global sqMRI score. The sqMRI scores were associated with concurrent, but not future or past motor GMFM-66 scores. Longitudinal changes in sqMRI scores were not associated with longitudinal changes in motor GMFM-66 scores. CONCLUSION: sqMRI scores of brain lesion extent at school-age are lower and a better indication of later-life motor functioning than very early life sqMRI scores. It may be best to interpret MRI white matter lesions with caution in very early life due to possible changes in lesion appearance and the unpredictable role of functional plasticity.

Neuroanatomical correlates of gross manual dexterity in children with unilateral spastic cerebral palsy.

Unilateral spastic Cerebral Palsy (UCP) results from congenital brain injury, and Magnetic Resonance Imaging (MRI) has a role in understanding the etiology and severity of brain insult. In UCP, functional impairment predominantly occurs in the upper limb (UL) of the more affected side, where manual ability and dexterity are typically reduced. Also, mirror movements (MMs), are often present in UCP, with a further possible negative functional impact. This study aims to investigate the relationships among neuroanatomical characteristics of brain injury at MRI, manual functional impairment and MMs, in children with UCP. Thirty-five children with UCP participated in the study (20, M = 15, F, mean age 9.2 ± 3.5 years). Brain lesions at MRI were categorized according to the Magnetic Resonance Classification System (MRICS) and by using a semi-quantitative MRI (sqMRI) scale. Gross manual performance was assessed through Manual Ability Classification System (MACS) and the Box and Block Test (BBT), and MMs by Woods and Teuber scale, for both hands. Non-parametric correlation analyses were run to determine the relationship between neuroanatomical and functional features. Regression models were run to explore the contribution of neuroanatomical features and MMs to UL function. Correlation analyses revealed moderate to strong associations between sqMRI scores contralateral to the more affected side and UL functional impairment on MACS and BBT, with more severe brain injuries significantly correlating with poorer function in the more affected hand. No association emerged between brain lesion severity scores and MMs. MRICS showed no association with MACS or BBT, while a significant correlation emerged between MRICS category and MMs in the more affected hand, with brain lesion category that are suggestive of presumed earlier injury being associated with more severe MMs. Finally, exploratory regression analyses showed that neuroanatomical characteristics of brain injury and MMs contributed to the variability of UL functional impairment. This study contributes to the understanding of the neuroanatomical and neurological correlates of some aspects of manual functional impairment in UCP by using a simple clinical brain MRI assessment.

Reorganization of visual fields after periventricular haemorrhagic infarction: potentials and limitations.

Visual functions are often impaired in preterm infants with periventricular haemorrhagic infarction, because of the involvement of the region where the optic radiations are located. In some cases an unexpected sparing of the visual fields has been described, and related to the plasticity of thalamo-cortical afferents that are supposedly able to bypass the lesion when it occurs in the early third trimester of gestation. We systematically reviewed the literature in the field to determine the limits and potentials of this type of reorganization. We found four studies meeting our criteria, from which we extracted case reports on 19 individuals with intraventricular haemorrhagic infarction. Eleven of the 19 did not have visual field defects, five had a bilateral visual field defect, and the remaining three had a unilateral visual field defect. The involvement of the optic radiations was often associated with normal visual fields as only one of the four individuals with damaged optic radiations showed visual field defects. Conversely, the presence of basal ganglia/thalamus involvement apparently prevented such reorganization, as the only two individuals with unilateral field restriction and available magnetic resonance imaging data both showed abnormalities in those structures. Consistent with this, we report on a further individual in which visual field restriction was associated with abnormal tractography on brain magnetic resonance imaging. Overall, this review supports the existence of effective mechanisms of plastic reorganization that allow a rewiring of geniculo-calcarine connections with restoration of full field vision but which are hindered by the involvement of the basal ganglia and thalamus.

Neonatal hypoxic-ischemic encephalopathy after acute carbon monoxide intoxication during pregnancy. A case report and brief review of the literature.

Carbon monoxide (CO) poisoning during pregnancy is a rare occurrence, associated with high maternal and fetal mortality rates. As CO can cross the placenta, leading to intrauterine hypoxia, CO intoxication can result in neurological sequelae and neurologic complications in fetuses who survive. We report a case of a preterm newborn acutely exposed to CO in-utero and delivered by emergent cesarean section at the 31st week of gestation due to the severe burns suffered by the mother following an indoor boiler explosion. As CO has serious adverse effects both on the mother and fetus, it is important to recognize and treat poisoning in a timely manner. Despite maternal blood CO levels, CO intoxication at critical stage of central nervous system development can lead to hypoxic-ischemic lesions, thus interdisciplinary care and follow up for these patients are mandatory.

Glycaemic Imbalances in Seizures and Epilepsy of Paediatric Age: A Literature Review.

Cerebral excitability and systemic metabolic balance are closely interconnected. Energy supply to neurons depends critically on glucose, whose fluctuations can promote immediate hyperexcitability resulting in acute symptomatic seizures. On the other hand, chronic disorders of sugar metabolism (e.g., diabetes mellitus) are often associated with long-term epilepsy. In this paper, we aim to review the existing knowledge on the association between acute and chronic glycaemic imbalances (hyper- and hypoglycaemia) with seizures and epilepsy, especially in the developing brain, focusing on clinical and instrumental features in order to optimize the care of children and adolescents and prevent the development of chronic neurological conditions in young patients.