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Background: Although psychomotor symptoms are associated with the clinical symptomatology of depression, they are rarely assessed and standardized clinical evaluation tools are lacking. Psychomotor retardation is sometimes assessed through direct patient observations by clinicians or through a clinical observation grid, in the absence of a standardized psychomotor assessment. In this pilot study, we evaluated the feasibility of standardized psychomotor examination of patients with major depressive disorder (MDD) and detailed a psychomotor semiology in these patients., Methods: We used a standardized psychomotor assessment to examine 25 patients with MDD and 25 age- and sex-matched healthy controls (HC) and compared their psychomotor profiles. Using standardized tests, we assessed muscle tone and posture, gross motor skills, perceptual-motor skills, and body image/organization. Clinical assessments of depressive symptoms (levels of psychomotor retardation, anxiety, and self-esteem) comprised this detailed psychomotor examination., Results: All participants were examined using the standardized psychomotor assessment. The main results of the psychomotor examination highlighted low body image of MDD participants (p < 0.001). Significant differences between groups were found in passive muscle tone, posture, emotional control, jumping, manual dexterity, walking, and praxis. Among these psychomotor variables, body image, passivity, jumping and rhythm scores predicted an MDD diagnosis., Conclusions: Beyond the psychomotor retardation known to be present in MDD patients, this examination revealed an entire psychomotor symptomatology characterized by elevated muscle tone, poor body image associated with poor self-esteem, slowness in global motor skills and manual praxis, and poor rhythmic adaptation. In light of these results, we encourage clinicians to consider using a standardized tool to conduct detailed psychomotor examination of patients with depressive disorders., Trial Registration: ClinicalTrials.gov identifier: NCT04031937 , 24/07/2019., (© 2022. The Author(s).)

AGC1/Aralar/Slc25a12 is the mitochondrial carrier of aspartate-glutamate, the regulatory component of the NADH malate-aspartate shuttle (MAS) that transfers cytosolic redox power to neuronal mitochondria. The deficiency in AGC1/Aralar leads to the human rare disease named "early infantile epileptic encephalopathy 39" (EIEE 39, OMIM # 612949) characterized by epilepsy, hypotonia, arrested psychomotor neurodevelopment, hypo myelination and a drastic drop in brain aspartate (Asp) and N -acetylaspartate (NAA). Current evidence suggest that neurons are the main brain cell type expressing Aralar. However, paradoxically, glial functions such as myelin and Glutamine (Gln) synthesis are markedly impaired in AGC1 deficiency. Herein, we discuss the role of the AGC1/Aralar-MAS pathway in neuronal functions such as Asp and NAA synthesis, lactate use, respiration on glucose, glutamate (Glu) oxidation and other neurometabolic aspects. The possible mechanism triggering the pathophysiological findings in AGC1 deficiency, such as epilepsy and postnatal hypomyelination observed in humans and mice, are also included. Many of these mechanisms arise from findings in the aralar -KO mice model that extensively recapitulate the human disease including the astroglial failure to synthesize Gln and the dopamine (DA) mishandling in the nigrostriatal system. Epilepsy and DA mishandling are a direct consequence of the metabolic defect in neurons due to AGC1/Aralar deficiency. However, the deficits in myelin and Gln synthesis may be a consequence of neuronal affectation or a direct effect of AGC1/Aralar deficiency in glial cells. Further research is needed to clarify this question and delineate the transcellular metabolic fluxes that control brain functions. Finally, we discuss therapeutic approaches successfully used in AGC1-deficient patients and mice.

The phenotypic variability associated with pathogenic variants in Lysine Acetyltransferase 6B (KAT6B, a.k.a. MORF, MYST4) results in several interrelated syndromes including Say-Barber-Biesecker-Young-Simpson Syndrome and Genitopatellar Syndrome. Here we present 20 new cases representing 10 novel KAT6B variants. These patients exhibit a range of clinical phenotypes including intellectual disability, mobility and language difficulties, craniofacial dysmorphology, and skeletal anomalies. Given the range of features previously described for KAT6B-related syndromes, we have identified additional phenotypes including concern for keratoconus, sensitivity to light or noise, recurring infections, and fractures in greater numbers than previously reported. We surveyed clinicians to qualitatively assess the ways families engage with genetic counselors upon diagnosis. We found that 56% (10/18) of individuals receive diagnoses before the age of 2 years (median age = 1.96 years), making it challenging to address future complications with limited accessible information and vast phenotypic severity. We used CRISPR to introduce truncating variants into the KAT6B gene in model cell lines and performed chromatin accessibility and transcriptome sequencing to identify key dysregulated pathways. This study expands the clinical spectrum and addresses the challenges to management and genetic counseling for patients with KAT6B-related disorders., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Rationale: The chikungunya virus (CHIKV) was first isolated in a Tanzanian epidemic area between 1952 and 1953. The best description of the CHIKV transmission during pregnancy can be found in a well-documented epidemic in 2005, in the "La Reunion" island, a French territory located in the Indian Ocean, in which about one-third of the population was infected. Reports of arbovirus infections in pregnancy are increasing over time, but the spectrum of clinical findings remains an incognita among researchers, including CHIKV., Patient Concerns: In this report, it was possible to verify 2 cases exposed to CHIKV during foetal period and the possible implications of the infection on gestational structures and exposed children after the birth., Diagnosis: In both cases, the mothers were positive by laboratory tests in serologic analysis for CHIKV, as ezyme-linked immunossorbent assay (ELISA), plaque reduction neutralisation testing (PRNT) and immunofluorescence (IF); but there were no positive tests in quantitative polymerase chain reaction (qPCR) for mothers or children., Interventions: The exposed children were followed up in a paediatrics clinic in order not only to provide the medical assistance, but also to verify child development and the possible implications and neurocognitive changes caused by gestational infection., Outcomes: There were neurological and developmental changes in one of the children followed up on an outpatient basis. There was an improvement in the neurological situation and symptoms only 3 years and 1 month after birth., Lessons: Based on the cases presented, we can conclude that clinical symptoms of CHIKV maternal infection may occur late in new-borns and can affect their development., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Premature babies are a special group at risk of persistent brain damage caused by diseases, the most serious of which are cerebral palsy(CP), autism spectrum disorders (ASD) and mental retardation, among others. These conditions may occur concurrently, but appear more often as separate disease syndromes in the same group of at-risk children. Long-term observation of psychomotor development by an interdisciplinary medical team closely cooperating with parents is necessary. It is important to detect the risk of developing these diseases as soon as possible in all development spheres., Material and Methods: The research was conducted to demonstrate the prognostic value of 'red flags' of developmental milestones and the ability to detect early signs of risk of developing CP and ASD in extremely premature babies. In this preliminary study, 42 preterm babies, born after less than 32 weeks pregnancy participated., Results: The occurrence of 'red flags'in the spheres: gross motor, fine motor and cognitive at 9 months was strongly associated with their presence at 24 months. The sensitivity and specificity were: gross motor - 0.91 (95% CI: 0.59, 1.00) and 0.94 (95% CI: 0.79, 0.99); fine motor - 0.83 (95% CI 0.36-1.00) and 1.00 (95% CI: 0.90-1.00); cognitive - 1.00 (0.40, 1.00) and 0.97 (0.86, 1.00). Other spheres had lower sensitivity but high specificity., Conclusions: The conclusion is that the 'red flags'at the 9 months milestones already predict the normal or developmental delay of premature babies, and predict the risk of CP and ASD. Due to the availability and lack of the need for specialized and costly training, it is worth considering their use in everyday life medical practice.

Objective: To explore the genetic basis for a child with ocular anomaly, microcephaly, growth retardation and intrauterine growth restriction., Methods: The patient underwent ophthalmologic examinations including anterior segment photography, fundus color photography, and fundus fluorescein angiography. The patient and her parents were subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis., Results: The patient was found to have bilateral persistent pupillary membrane and coloboma of inferior iris, in addition with macular dysplasia and radial pigmentation near the hemal arch of the temporal retina. She was found to have carried compound heterozygous missense variants of the PHGDH gene, namely c.196G>A and c.1177G>A, which were respectively inherited from her father and mother. Bioinformatic analysis suggested both variants to be pathogenic., Conclusion: The patient was diagnosed with phosphoglycerate dehydrogenase deficiency. Above finding has enriched the phenotypic spectrum of the disease with ocular manifestations.

Background: Contrasting findings were reported in several animal models with a Shank3 mutation used to induce various autism spectrum disorder (ASD) symptoms. Here, we aimed at investigating behavioral, cellular, and molecular consequences of a C-terminal (frameshift in exon 21) deletion in Shank3 protein in mice, a mutation that is also found in clinical conditions and which results in loss of major isoforms of Shank3. A special focus was made on cerebellar related parameters., Methods: All three genotypes were analyzed [wild type (WT), heterozygote (Shank3+/ΔC) and homozygote (Shank3 ΔC/ΔC)] and males and females were separated into two distinct groups. Motor and social behavior, gait, Purkinje cells (PC) and glutamatergic protein levels were determined. Behavioral and cellular procedures used here were previously validated using two environmental animal models of ASD. ANOVA and post-hoc analysis were used for statistical analysis., Results: Shank3 ΔC/ΔC mice showed significant impairments in social novelty preference, stereotyped behavior and gait. These were accompanied by a decreased number of PC in restricted cerebellar sub-regions and decreased cerebellar expression of mGluR5. Females Shank3 ΔC/ΔC were less affected by the mutation than males. Shank3+/ΔC mice showed impairments only in social novelty preference, grooming, and decreased mGluR5 expression and that were to a much lesser extent than in Shank3 ΔC/ΔC mice., Limitations: As Shank3 mutation is a haploinsufficiency, it is of interest to emphasize that Shank3+/ΔC mice showed only mild to no deficiencies compared to Shank3 ΔC/ΔC., Conclusions: Our findings indicate that several behavioral, cellular, and molecular parameters are affected in this animal model. The reported deficits are more pronounced in males than in females. Additionally, male Shank3 ΔC/ΔC mice show more pronounced alterations than Shank3+/ΔC. Together with our previous findings in two environmental animal models of ASD, our studies indicate that gait dysfunction constitutes a robust set of motor ASD symptoms that may be considered for implementation in clinical settings as an early and quantitative diagnosis criteria.

Introduction: Falls among older people are a major health issue and the first cause of accidental death after 75 years of age. Post-fall syndrome (PFS) is commonly known and yet poorly studied., Objective: Identify risk factors for PFS and do a follow-up 1 year later., Methods: We included all patients over 70 years of age hospitalized after suffering a fall in a case-control study, and then followed them in a cohort study. PFS was retained in case of functional mobility decline (transferring, walking) occurring following a fall in the absence of an acute neurological, orthopedic or rheumatic pathology directly responsible for the decline. The data initially collected were: clinical (anamnestic, emergency and departmental/ward evolution, medical history, lifestyle, treatments, clinical examination items); and imaging if the patient had been subjected to brain imaging in the last 3 years prior to inclusion. Regarding the follow-up at 1 year, we collected from the general physician the occurrence and the characteristics of new falls, functional mobility assessment, hospitalization and death., Results: Inclusion took place from March 29, 2016 to June 7, 2016 and follow-up until June 30, 2017. We included 70 patients. A total of 29 patients exhibited a PFS (41.4 %). Risk factors for PFS included age, walking disorder prior to the fall, the use of a walking aid prior to the fall, no unaccompanied outdoor walk in the week before the fall, visual impairment making close reading impossible, stiffness in ankle dorsiflexion, grip strength and the fear of falling. Among patients with PFS, 52.9% could still perform a transfer at 1 year and 64.7% could still walk against 80.7% and 85.2%, respectively, for patients without PFS., Conclusion: The study showed the existence of body functions/structure impairments and activity limitations prior to the fall among patients exhibiting a PFS. This suggests the existence of a pre-fall syndrome, i.e., a psychomotor disadaptation syndrome existing prior to the fall. Among the 8 risk factors, fear of falling, vision impairment and muscle strength could be targeted for improvement. The diagnosis of PFS could be a marker of loss of functional mobility at 1 year., (© 2020 S. Karger AG, Basel.)

Purine-rich element-binding protein A (PURA) encodes Pur-alpha, a transcriptional activator protein is crucial for normal brain development. Pathogenic variants in PURA are known to cause mental retardation, autosomal dominant 31, characterized by psychomotor delay, absent or poor speech, hypotonia, feeding difficulties, seizures or 'seizure-like' movements, and dysmorphism. PURA-related neurodevelopmental disorder (PURA-related NDD) result either from heterozygous pathogenic sequence variants in PURA or microdeletions spanning PURA. Singleton whole-exome sequencing (WES) was performed for the proband after a clinical diagnosis of infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) was made. The pathogenic variant was validated by Sanger sequencing in the proband and parents. Comparison of PURA-related NDD and IHPRF was carried out. WES identified a novel, de-novo stop-gain variant c.178G>T in PURA. In addition to typical phenotype, subject also had hypersensitivity to various stimuli which was not reported in PURA-related NDD. Significant phenotypic overlap was observed in subjects with PURA-related NDD and IHPRF especially with IHPRF2, caused by biallelic pathogenic variants in UNC80. This study expands the phenotypic and mutational spectrum of PURA-related NDD. We propose PURA-related NDD to be considered as a close differential diagnosis of IHPRF.

Introduction: The rate of premature births has significantly increased, and it is important to determine its effects. The objective of this study is to determine the psychomotor development profile of a group of children born prematurely, at the age of 4, 5 and 6, and to compare them with a group of full-term birth children, in order to detect any differences., Patients and Methods: The sample consisted of 98 participants, evenly distributed into two groups, premature and full-term born children. A prospective longitudinal observational analytical study, with a design of cases and controls, was carried out. For some analyses, the separation into early pre-term, moderate pre-term, and late pre-term was considered. The evaluations were performed using the McCarthy Scale of Aptitudes and Psychomotor skills for children., Results: The data shows achievements within the middle intervals. However, there are more difficulties in development at 4 years in the group of premature children, according to gestational age. Early pre-term (gestational age less than 32 weeks) showed significantly lower scores compared to moderate and late pre-term, mainly at 6 years, and with those born at term, at 4 and 6 years., Conclusions: Development difficulties are greater at a lower gestational age, and may affect the Primary Education stage. The need to monitor all premature children in the preschool stage is suggested, as well as to evaluate more specific skills and continue with the care from specialist teams., (Copyright © 2020 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Purpose: Direct assessment of trainee performance across time is a core tenet of competency-based medical education. Unlike variability of psychomotor skills across levels of expertise, performance variability exhibited by a particular trainee across time remains unexplored. The goal of this study was to document the consistency of individual surgeons' technical skill performance., Method: A secondary analysis of assessment data (collected in 2010-2012, originally published in 2015) generated by a prospective cohort of participants at Montreal Children's Hospital with differing levels of expertise was conducted in 2017. Trained raters scored blinded recordings of a myringotomy and tube insertion performed 4 times by junior and senior residents and attending surgeons over a 6-month period using a previously reported assessment tool. Descriptive exploratory analyses and univariate comparison of standard deviations (SDs) were conducted to document variability within individuals across time and across training levels., Results: Thirty-six assessments from 9 participants were analyzed. The SD of scores for junior residents was highly variable (5.8 out of a scale of 30 compared with 1.8 for both senior residents and attendings [F(2,19) = 5.68, P < 0.05]). For a given individual, the range of scores was twice as large for junior residents than for senior residents and attendings., Conclusions: Surgical residents may display highly variable performances across time, and individual variability appears to decrease with increasing expertise. Operative skill variability could be underrepresented in direct observation assessment; emphasis on an adequate amount of repetitive evaluations for junior residents may be needed to support judgments of competence or entrustment.

Objective: The aim of this study is to explore the utility of rapid medical trio exome sequencing (ES) for prenatal diagnosis using the skeletal dysplasia as an exemplar., Method: Pregnant women who were referred for genetic testing because of ultrasound detection of fetal abnormalities suggestive of a skeletal dysplasia were identified prospectively. Fetal samples (amniocytes or cord blood), along with parental blood, were send for rapid copy number variations testing and medical trio ES in parallel., Results: Definitive molecular diagnosis was made in 24/27 (88.9%) cases. Chromosomal abnormality (partial trisomy 18) was detected in one case. Sequencing results had explained the prenatal phenotype enabling definitive diagnoses to be made in 23 cases. There were 16 de novo dominant pathogenic variants, four dominant pathogenic variants inherited maternally or paternally, two recessive conditions with pathogenic variants inherited from unaffected parents, and one X-linked condition. The turnaround time from receipt of samples in the laboratory to reporting sequencing results was within 2 weeks., Conclusion: Medical trio ES can yield very timely and high diagnostic rates in fetuses presenting with suspected skeletal dysplasia. These definite diagnoses aided parental counseling and decision making in most of cases., (© 2020 John Wiley & Sons, Ltd.)

Deletion of the 1q43q44 chromosomal region has been related to a clinical syndrome characterized by neurodevelopmental delay, intellectual disability, microcephaly, congenital abnormality of the corpus callosum, and epilepsy and dysmorphic features. A wide variability of the clinical features have been linked to the contiguous deleted genes and incomplete penetrance has been observed too. Here, we report a 4-years-old boy with microcephaly, neurodevelopmental delay, and cardiac atrial septal defect, who had a de-novo 117 Kb 1q43-q44 microdeletion. The deleted chromosomal region encompassed the two genes SDCCAG8 and AKT3. The characteristics of the deletion and the clinical condition of the patient suggest a pathogenic role of the 1q43-q44 deletion, supporting a pivotal role of AKT3 gene in the expression of the clinical phenotype.

Case: We are reporting the third unrelated case of cerebral aspartate-glutamate carrier isoform 1 (AGC1) deficiency. Patient is a 21-month-old Yemeni male who presented with refractory seizure disorder and developmental arrest. Neuroimaging showed cerebral volume loss and diminished N-acetylaspartate (NAA) peak. Whole exome sequencing revealed a homozygous novel missense variant in the SLC25A12 gene. Patient's seizure frequency abated drastically following initiation of ketogenic diet., Discussion and Conclusion: Cerebral AGC1 deficiency results in dysfunction of mitochondrial malate aspartate shuttle, thereby prohibiting myelin synthesis. There are significant phenotypic commonalities between our patient and previously reported cases including intractable epilepsy, psychomotor delay, cerebral atrophy, and diminished NAA peak. Our report also provides evidence regarding beneficial effect of ketogenic diet in this rare neurometabolic epilepsy., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Vitamin B 12 (cobalamin, cbl) deficiency in children is rare and may occurs in exclusively breast fed infants of mothers on vegetarian or vegan diet with lack of appropriate supplementation. The clinical manifestation of vitamin B12 deficiency include neurological disorders, megaloblastic anemia and failure to thrive. Routine and commonly used laboratory tests such as cell blood count (CBC) or serum vitamin B 12 level are sufficient for appropriate diagnosis. Typical therapy is based on intramuscular cobalamin injections. Early diagnosis and early onset of treatment are crucial factors for long-term prognosis of patients as the duration of deficiency may be correlated with the development of long lasting changes in the nervous system. The purpose of this article is to present influence of maternal vitamin B 12 deficiency as a cause of infant psychomotor retardation., Case Presentation: We report the case of a 7 months old girl whose parents sought medical advice due to pathological somnolence and developmental regression of their daughter with onset approximately 2 months prior to the visit. Following several diagnostic tests it was determined that the infant's symptoms were due to vitamin B 12 deficiency which was secondary to the mother's latent Addison-Biermer disease. Apart from neurological symptoms the infant also showed megaloblastic anemia which is typical to cobalamin deficiencies. Intramuscular vitamin B 12 supplementation resulted in instant improvement of the patient's general condition and blood morphology. Unfortunately, psychological examination indicated long-term psychomotor retardation due to delayed diagnosis of B 12 deficiency., Conclusions: Vitamin B 12 levels should be considered during differential diagnosis of neurological symptoms in exclusively breast-fed infants especially if they co-exist with megaloblastic anemia and psychomotor retardation.

Objective: Benzodiazepines impair driving ability and psychomotor function. Eyelid parameters accurately reflect drowsiness; however, the effects of benzodiazepines on these measures have not been extensively studied. The aim of this study was to investigate the effect of benzodiazepines on eyelid parameters and evaluate their accuracy for detecting psychomotor impairment., Methods: Eyelid parameters were recorded during a psychomotor vigilance task (PVT) and driving simulation over 2 days, baseline, and after 20-mg oral temazepam. The utility of eyelid parameters for detecting PVT lapses was evaluated using receiver operating characteristic curves, and cut-off levels indicating impairment (≥1 and ≥2 PVT lapses per min) were identified. The accuracy of these cut-off levels for detecting driving simulator crashes was then examined., Results: PVT and driving simulator performance was significantly impaired following benzodiazepine administration (p < .05). Average eyelid closure duration (inter-event duration) was a reliable indicator of PVT lapses (area under the curve [AUC] of 0.87-0.90). The cut-off value of eyelid closure duration derived from PVT AUC was able to predict driving simulator crashes with moderately high sensitivity and specificity (76.23% and 75.00%)., Conclusions: Eyelid parameters were affected by benzodiazepines and accurately detected the psychomotor impairment. In particular, eyelid closure duration is a promising real-time indicator of benzodiazepine impairment., (© 2020 John Wiley & Sons Ltd.)

Fumarate hydratase deficiency (FHD) is a rare metabolic disease caused by two defective copies of the FH gene, which encodes the Krebs cycle enzyme fumarase. FHD is associated with brain and developmental abnormalities, seizures, and high childhood mortality. We describe the symptoms and treatment of a patient with FHD. While infantile spasms are common in FHD, the patient presented with epileptic spasms later in childhood. Also unexpectedly, the patient responded excellently to lacosamide for her non-convulsive status epilepticus and epileptic spasms after three first-line medication trials failed. We biochemically analyzed the patient's two fumarase variants (E432Kfs*17 and D65G). While E432Kfs*17 was extremely enzymatically defective, D65G exhibited only a mild defect, possibly playing a role in the patient's longer survival., (© 2019 Wiley Periodicals, Inc.)

Background: Excessive daytime sleepiness plays an important role in the presentation and course of mood disorders. Standard objective measures of daytime sleep propensity are of little to no value in depressive illness. This study examined the psychomotor vigilance task (PVT), an objective measure of neurobehavioral alertness, and its cross-sectional and longitudinal associations with depressive symptomatology in the Wisconsin Sleep Cohort Study., Methods: The sample consisted of 1569 separate 10-min PVT assessments conducted in 942 unique individuals. Cross-sectional and longitudinal conditional logistic regression models were used to estimate associations between the primary outcome of depression symptomatology (adjusted Zung scale≥50) and six separate PVT variables: mean reciprocal reaction time (1/RT); total lapses (RTs≥500 msec; LAPSE); total false responses (FALSE); reciprocal of the mean of the 10% fastest (FAST) and 10% slowest (SLOW) RTs; and slope of the linear regression line for all transformed 1/RTs (SLOPE)., Results: In fully-adjusted cross-sectional models, 1/RT, LAPSE, FAST, and SLOW were each significantly associated with depression, such that worse neurobehavioral alertness was associated with higher odds of depressive symptomatology. Similar, though attenuated, findings were observed in fully-adjusted conditional longitudinal models that examined within-subject changes in depression status in the subset of participants with repeated PVT assessments. FALSE and SLOPE were not associated with depression in either cross-sectional or conditional longitudinal models., Conclusions: These findings suggest components of the PVT are associated with depressive symptomatology. Further research is indicated to clarify the role of the PVT in the assessment of hypersomnolence in mood disorders., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: This study reviews the scientific literature to identify and describe which assessment tools (ATs) are used in pediatric oncology and neuro-oncology rehabilitation and which development neuropsychomotor (DNPM) ATs were built for children with central nervous system (CNS) tumors., Methods: A systematic review was performed searching PubMed, CINAHL, PEDro, Science Direct, and Catalog of National Institute of Tumors databases and specialized journals. The search covered 7 years (2010-2017) and used relevant keywords in different combinations. A further search was carried out on DNPM rehabilitation manuals and academic thesis., Results: The review retrieved 35 eligible articles containing 63 ATs. The most common ATs were the Behavioral Rating Inventory of Executive Function (BRIEF) and the Wechsler Intelligence Scale for Children (WISC). Most of the ATs covered a single area of child development among behavioral/psychological, cognitive, and motor areas. A total of 159 ATs were found in manuals and thesis, and only 17 of them were already identified in the journal search. None of the ATs identified in both searches had been specifically developed for children with CNS tumor., Conclusion: The results highlight the need to develop and validate a global multidimensional AT for children with CNS tumor, overcoming the fragmentation of the assessment procedures and promoting standardized rehabilitation protocols.

Introduction: Cerebellar injury is increasingly recognized as a relevant complication of premature birth. However, the prevalence of reduced cerebellar growth and its consequences for neurodevelopmental outcome in preterm infants without overt brain injury remain to be defined in detail. The aim of this study was to assess the transcerebellar diameter (TCD) at term-equivalent age (TEA) in very preterm infants without brain injury and to evaluate whether TCD is related to neurodevelopmental outcome in this population., Methods: Very preterm infants underwent magnetic resonance imaging at TEA. Infants with any grade of supra- or infratentorial brain injury were excluded. TCD was measured and categorized using existing cut-off values as normal TCD and mild or severe TCD reduction. Psychomotor Developmental index (PDI) and Mental Developmental index (MDI) were assessed using Bayley Scales of Infant Development II and III at a corrected age of 2 years., Results: A total of 166 infants with a mean gestational age of 29.9 ± 1.8 weeks and a mean birth weight of 1,317 ± 393 g were included. Mean TCD of girls was significantly lower compared to the mean TCD of boys (p = 0.004). TCD reduction was present in 8 infants (4.8%). Infants with a mild TCD reduction achieved lower mean MDI than infants with normal TCD (p = 0.021)., Discussion: We found that reduced TCD was associated with a 17% lower mean MDI at a corrected age of 2 years. Thus, TCD at TEA may be used as an imaging marker for adverse cognitive outcome in the apparently low-risk group of preterm infants without brain injury., (© 2019 S. Karger AG, Basel.)

Background: It is not uncommon that an infant with a disease of unknown etiology is presented to a physician. Facial dysmorphic features lead to a different diagnosis. It is a challenge to link the presentation to the newfound diagnosis., Case Presentation: A 37-day-old Yemenite Jewish girl was presented to our institution with a clinical picture of pseudohypoaldosteronism due to abnormal facial features and a psychomotor developmental delay. Further investigation led to the diagnosis of CDK13-related disorder. According to the literature, CDK13 has a key role in the cell cycle, but no interference with the aldosterone signaling pathway or electrolyte balance was described. No mutations in the previously described gene NR3C2 (cytogenetic location 4q31.23), encoding the mineralocorticoid receptor, were found. Although the clinical presentation corresponded to pseudohypoaldosteronism type 1, we could not genetically confirm this., Conclusions: Probably pseudohypoaldosteronism was a coincidental finding in this girl with a CDK13 mutation, but because only limited information is known about CDK13-related disorders, further investigation could be more informative to clarify this presentation.

Objective: Leptin is critical for central nervous system development and maturation. This study aimed to evaluate the potential regulatory role of cord leptin in the neuropsychomotor development of children ages 18 months to 6 years., Methods: This study included 424 children from a prospective mother-child cohort (Rhea Study; Crete, Greece) with available cord leptin levels and data on neurodevelopmental outcomes at 18 months (Bayley Scales of Infant and Toddler Development, Third Edition), 4 years (McCarthy Scales of Children's Abilities), and 6 years (Raven's Coloured Progressive Matrices and Trail Making Test). Multivariable linear regression models were used to explore the associations., Results: Each 10-ng/mL increase in the cord leptin level was associated with increased scores on the gross motor scale at 18 months (β coefficient: 3.8; 95% CI: 0.0-7.5), with decreased scores in the general cognitive performance (β coefficient: -3.0; 95% CI: -5.5 to -0.4), perceptual performance (β coefficient: -3.4; 95% CI: -6.0 to -9.9), working memory (β coefficient: -3.1; 95% CI: -5.7 to -0.4), executive function (β coefficient -3.1; 95% CI: -5.7 to -0.5), and functions of the posterior cortex (β coefficient: -2.7; 95% CI: -5.2 to -0.1) scales at 4 years, and with a 3.7-unit decrease in the Raven's Coloured Progressive Matrices score at 6 years (β coefficient: -3.7; 95% CI: -6.9 to -0.5)., Conclusions: Increased cord leptin levels are associated with enhanced gross motor development at 18 months but decreased cognitive performance in early and middle childhood., (© 2019 The Obesity Society.)

Introduction : The ability to accurately perceive human movement is fundamental to social functioning and known to be influenced by one's own motor skills. In Autism Spectrum Disorder (ASD), there is ongoing debate about whether human movement perception is impaired. Given that motor skills vary considerably among these individuals, it may be that human movement perception is differentially affected as a function of motor proficiency. The aim of the current study was, thus, to explore whether individuals with ASD with and without motor difficulties differ in the way they visually attend to and perceive human movement. Method : Three groups of children aged 6 to 14 completed the study: an ASD group with motor difficulties (ASD MD ), an ASD group without motor difficulties (ASD NMD ), and a typically-developing control group (TD). All participants ( N = 31) underwent eye-tracking while they viewed communicative interactions performed by two point-light actors. Primary analyses considered group differences in perceptual accuracy and gaze patterns. Results : Results revealed poorer perceptual accuracy in the ASD MD group compared to the ASD NMD and TD groups. Both ASD groups also exhibited gaze anomalies. Unlike the ASD NMD and TD groups who preferentially allocated their gaze to the actor initiating the interaction, the ASD MD group gazed at both actors equally. In contrast, the ASD NMD group shifted their gaze between the actors more frequently than the other groups. Conclusions : These preliminary findings suggest that individuals with ASD and co-occurring motor difficulties employ an atypical attentional style that may hinder accurate human movement perception, whereas those without motor difficulties may employ a compensatory attentional style that facilitates typical perception. Improving our understanding of how attention and perception are affected across the ASD spectrum has the potential to provide insight into the mechanisms that underlie the core social deficits that define this disorder.

Posterior cortical atrophy (PCA) is a rare form of dementia primarily characterized by slowly progressing deterioration of visual processing corresponding to atrophy in the posterior parietal and occipital cortices with less prominent memory loss than are usually seen in other forms of dementia such as Alzheimer's Disease (AD). In the present case report, we describe longitudinal data over a period of 11 years regarding clinical and neuropsychological impairments and their relation to the location and extent of cortical changes related to higher order visual processing in a patient with posterior cortical atrophy. In our patient, visual processing deficits concerning space, motion and object perception emerged at the age of 50 and continued to worsen. By the age of 58, while the perception of contrast, color and figure-ground separation appeared undisturbed the patient exhibited pronounced dorsal- and ventral-related visual deficits, which continued to worsen with age. The patient's MRI scans over the course of the disease revealed increasing circumscribed and bilateral atrophy of the parietal and occipital cortices, with a right-sided predominance. The specific localization of cortical atrophy, the slow progression characterized by visual processing deficits and relatively preserved memory were the main criteria for the diagnosis of posterior cortical atrophy. The case report also highlights the importance of an early extensive neurological and neuropsychological evaluation of visual deficits that occur without the presence of ophthalmological disease.

Background: Bainbridge-Ropers syndrome is a rare autosomal dominant genetic disorder., Case Characteristics: A 26-day-old neonate presented with feeding difficulties, excessive sleeping, and hirsutism over forehead and lumbosacral skin., Outcome: Whole-exome sequencing identified a novel nonsense mutation., Message: We report a novel mutation in a Chinese neonate with Bainbridge-Ropers syndrome.

Introduction: Psychomotor impairments in Autism Spectrum Disorders (ASD) have frequently been described in scientific literature. Such deficits impact upon the development of social motor function and interfere with the ability to adjust to everyday life. The inclusion of sensory-motor signs in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) confirms their importance in the diagnosis of ASD. Previous literature has shown the presence precocity of these signs, sometimes before the alteration of the social communication. To our knowledge, there are no existing clinical tools to measure sensory-psychomotor deficit, specifically in ASD. The current paper presents the construction and validation of a new scale, designed to evaluate sensory-psychomotor signs in Autism: 'the Sensory-psychomotor Particularities Scale in Autism' (SPSA)., Method: The scale is composed of 160 items describing common sensory-psychomotor signs in autism. These items are grouped into 20 variables: touch, nociception, vestibular sensitivity, proprioceptive sensitivity, vision, auditory, multimodality, tone, posture, balance, global coordination, manual dexterity, body schema, bodily self-consciousness, relational adjustment, emotional expression, use of objects, space, time and tonico-emotional regulation. For each item, the psychomotor therapist evaluated sensori-psychomotor signs according to a five-level Likert scale (0="the sign is never expressed by the person", 1="weakly expressed", 2="moderately expressed", 3="severely expressed" and 4="the sign is very characteristic of the person and very severely expressed"). This is completed by a family interview in order to assess the impact of these signs on everyday situations. The study included 111 children with autism. The presence of neurological and genetic diseases was exclusion criteria. For each child, a global developmental evaluation was carried out by an expert clinical team specializing in ASD. Standardized clinical tools were used: Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS), Behavior Summarized Evaluation scale (BSE-R), Repeated and Restricted Behavior scale (RRB), Movement Assessment Battery for Children (M-ABC), Motor Development Rating scale (MDR), Sensory Profile (SP). Developmental quotients (DQ) were evaluated using various tests depending on age and ability., Results: Factor analysis produced three clinically relevant factors: F1: "sensory-emotional synchronization", F2: "multisensory integration" and F3: "motor skills": each containing a similar quantity of items. They account for roughly equal percentages of variance (18.9%, 18.0%, 16.8%, respectively). The factorial structure does not change if the 26 children with comorbid developmental coordination disorder are removed. The three factors show good internal consistency and excellent inter-rater reliability. F1 is comprised of 6 items: touch, nociception, proprioceptive sensitivity, vision, emotional expression and tonico-emotional regulation. This factor is significantly associated with items of the Sensory Profile (touch processing, poor registration, sensory seeking). F2 is comprised of 5 items: multimodality, bodily self-consciousness, relational adjustment, use of objects and space. This factor is associated with ADOS, BSE-R and RRB scores, and the item "touch processing" of the Sensory Profile. F3 is comprised of 4 items: tone, posture, global coordination, manual dexterity. This factor is associated with the M-ABC, the MDR and the item "low endurance" of the Sensory Profile., Conclusion: The SPSA is a relevant clinical tool to assess the severity of sensory-psychomotor clinical signs in order to describe the individual profiles of children with ASD. It represents a critical step in advancing knowledge of the complex and heterogeneous pattern of psychomotor development in autism. It could make a valuable contribution to the field, both in research and clinical practice., (Copyright © 2019 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Continuous spikes and waves during slow sleep (CSWS) is an EEG pattern that appears during childhood, and is often associated with cognitive impairment. It can appear in the course of epileptic syndromes, as well as in benign epilepsy. The aim of this study is to analyse epidemiological and clinical characteristic of patients with CSWS, in order to describe possible predictive factors in their outcome., Methods: A retrospective study was conducted on paediatric patients with CSWS treated in a third-level hospital from November 1997 to November 2017., Results: The study included 25 patients (68% male), of whom 76% had abnormalities in the neuroimaging or suffered from psychomotor development disorder (secondary CSWS). The rest were healthy, or diagnosed with idiopathic epilepsy. The mean age of onset of CSWS was 6.7 years, but earlier in the secondary CSWS cases. Symptoms were present during the CSWS episode in 72% of cases. All of them were treated with antiepileptic drugs, which were effective in 36%. CSWS stopped in 72%, and remission was longer if the CSWS onset occurred at an older age. One-third (33%) presented with sequelae, mostly cognitive and behavioural alterations. Outcome was poorer in those with secondary CSWS and, in those whose CSWS started at an earlier age and lasted longer., Conclusion: The CSWS pattern, although rare, is still a therapeutic challenge. A close follow-up of the patients with epilepsy is important, especially if associated with cognitive impairment, in order to establish an early diagnosis and treatment., (Copyright © 2019 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

We followed children at family risk of dyslexia and children with preschool language difficulties from age 3½, comparing them with controls (N = 234). At age 8, children were classified as having dyslexia or Developmental Language Disorder (DLD) and compared at earlier time points with controls. Children with dyslexia have specific difficulties with phonology and emergent reading skills in the preschool period, whereas children with DLD, with or without dyslexia, show a wider range of impairments including significant problems with executive and motor tasks. For children with both dyslexia and DLD, difficulties with phonology are generally more severe than those observed in children with dyslexia or DLD alone. Findings confirm that poor phonology is the major cognitive risk factor for dyslexia., (© 2019 The Authors. Child Development published by Wiley Periodicals, Inc. on behalf of Society for Research in Child Development.)

Introduction: In Chile, the prison system has a program that allows inmate mothers to live with their children un der two years of age. This could imply that these children are more exposed to stress conditions and a higher psychomotor developmental delay (PDD) risk., Objective: To compare the PDD and salivary cortisol concentrations (SCC) of children living in prison with their mothers and to compare the results with control children., Subjects and Method: Cross-sectional study in 42 infants, 12 of them are children of inmate mothers in the penitentiary center (CPF) of Santiago, and 30 controls from a Primary Care Family Health Center (CESFAM). PDD of infants was assessed through the ASQ-3 questionnaire and salivary cortisol was measured in infants and mothers using radioimmunoassay., Results: The median salivary cortisol level of the children of CPF and CESFAM mothers was 2.3 ng/ ml (IQR 1.1 to 2.7) and 2.1 ng/ml (IQR 1.6 to 2, 9) respectively. Maternal cortisol was 4.6 ng/ml (IQR 3.8 to 7.3) in the CPF and 3.7 ng/ml (IQR 2.4 to 4.7) in the CESFAM. The PDD deficit was 2.3% and 28.5% for children from the CPF and the CESFAM respectively, without statistical difference (p = 0.06)., Conclusions: There was no difference in the PDD and salivary cortisol between children of both groups.

Objectives: To evaluate whether the degree of hypoxemia following stage-I and stage-II palliative surgeries predicts neurodevelopmental outcomes at 14 months of age in children with single ventricle congenital heart disease (SVCHD)., Design: We analyzed longitudinal data from two Pediatric Heart Network (PHN) randomized controlled trials, with a total of 328 subjects. Oxygen saturations, measured via pulse oximetry, at time of discharge from stage-I and stage-II surgeries were the primary predictors of interest, and Bayley Scales of Infant Development-II (BSID-II) scores at 14 months old were the primary outcome measure. Relevant covariates from previously-published PHN studies were also included in regression models., Results: Oxygen saturations at time of discharge from stage-I and stage-II surgeries were not related to BSID-II scores. Having one or more oxygen saturation measurements below 80% was also not associated with BSID-II scores, and neither was change in oxygen saturations over time. These relationships were not altered by inclusion of relevant covariates., Conclusions: In this large cohort of children with SVCHD, oxygen saturations post-stage-I and post-stage-II palliation surgeries as measured via pulse oximetry were not associated with neurodevelopmental outcomes at 14 months of age. The relationship between oxygen saturations and neurodevelopment in SVCHD is likely complex, and neurodevelopment is known to be affected by a number of factors. Pulse oximetry may also be an insufficient proxy for cerebral oxygen delivery. Clinically, pulse oximetry readings during the interstage and post-stage-II surgery periods are not a reliable predictor of future neurodevelopmental risk., (© 2019 Wiley Periodicals, Inc.)

Background: Impairments in dexterity after stroke are commonly assessed by the Nine Hole Peg Test (NHPT), where the only outcome variable is the time taken to complete the test. We aimed to kinematically quantify and to compare the motor performance of the NHPT in persons post-stroke and controls (discriminant validity), to compare kinematics to clinical assessments of upper extremity function (convergent validity), and to establish the within-session reliability., Methods: The NHPT was modified and standardized (S-NHPT) by 1) replacing the original peg container with an additional identical nine hole pegboard, 2) adding a specific order of which peg to pick, and 3) specifying to insert the peg taken from the original pegboard into the corresponding hole of the target pegboard. Eight optical cameras registered upper body kinematics of 30 persons post-stroke and 41 controls during the S-NHPT. Four sequential phases of the task were identified and analyzed for kinematic group differences. Clinical assessments were performed., Results: The stroke group performed the S-NHPT slower (total movement time; mean diff 9.8 s, SE diff 1.4), less smoothly (number of movement units; mean diff 0.4, SE diff 0.1) and less efficiently (path ratio; mean diff 0.05, SE diff 0.02), and used increased scapular/trunk movements (acromion displacement; mean diff 15.7 mm, SE diff 3.5) than controls (P < 0.000, r ≥ 0.32), indicating discriminant validity. The stroke group also spent a significantly longer time grasping and releasing pegs relative to the transfer phases of the task compared to controls. Within the stroke group, kinematics correlated with time to complete the S-NHPT and the Fugl-Meyer Assessment (r s 0.38-0.70), suggesting convergent validity. Within-session reliability for the S-NHPT was generally high to very high for both groups (ICCs 0.71-0.94)., Conclusions: The S-NHPT shows adequate discriminant validity, convergent validity and within-session reliability. Standardization of the test facilitates kinematic analysis of movement performance, which in turn enables identification of differences in movement control between persons post-stroke and controls that may otherwise not be captured through the traditional time-based NHPT. Future research should ascertain further psychometric properties, e.g. sensitivity, of the S-NHPT.

Objective: To explore the correlations between observer ratings and instrumental parameters across domains of psychomotor functioning in depression., Method: In total, 73 patients with major depressive disorder underwent extensive psychomotor and clinical testing. Psychomotor functioning was assessed with (i) an observer-rated scale (the CORE measure) and also objectively with (ii) 24-h actigraphy, and (iii) a fine motor drawing task., Results: Observer ratings of retardation correlated with instrumental assessments of fine and gross motor functioning. In contrast, observer ratings of agitation did not correlate with observer ratings of retardation or with the instrumental measures. These associations were partly influenced by age and, to a lesser extent, by depression severity., Conclusion: Psychomotor disturbance is a complex concept with different manifestations in depressed patients. Although observer ratings of retardation correspond well with instrumental measures of the motor domains, objective measurement of agitation and other aspects of psychomotor disturbance require further research.

Upper limb deficits are common sequelae after a stroke and negatively affect daily living and quality of life. The use of outcome measures to evaluate upper limb function is essential to assess sensorimotor recovery and to determine the effectiveness of rehabilitation. The aim of this study was to estimate the construct validity and inter-rater reliability of three shortened versions of the Singapore version of the Chedoke Arm and Hand Activity Inventory (CAHAI-SG) comprising seven, eight, and nine test items. The sample consisted of 55 inpatients with acute/subacute stroke to whom the CAHAI-SG, Fugl-Meyer Assessment of Upper Extremity (FMA-UE) and the Action Research Arm Test (ARAT) were administered. To estimate convergent and discriminative construct validity, Spearman's rank correlation coefficient and 95% confidence intervals were computed for CAHAI-SG scores with FMA-UE and ARAT scores. Reliability was estimated using intraclass correlation coefficient (relative reliability) and the standard error of measurement (absolute reliability). Convergent validity with the FMA-UE was 0.79, 0.80, and 0.81 for seven-item, eight-item, and nine-item versions of the CAHAI-SG, respectively, and 0.81 with the ARAT for all shortened versions. Discriminative validity with the FMA-UE pain subscale was between 0.37 and 0.38. The absolute reliability was 3.09, 3.65, and 3.98, and relative reliability was 0.96, 0.95, and 0.96 for the seven-item, eight-item, and nine-item versions, respectively. All shortened versions of the CAHAI-SG demonstrated similar psychometric properties to the full (13 item) version, meaning clinicians may use these shorter versions that require less time to administer and score.

Aim: To describe neurobehavioral patterns in neonates with congenital heart disease (CHD)., Method: A cohort study describing neurobehavioral performance of neonates with CHD requiring cardiac surgery. The neonates were evaluated preoperatively and postoperatively with the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) and scores were compared with published normative values. Clinical factors were obtained by chart review to assess their association with behavior. The CHD NNNS score pattern was compared with previously reported profiles in other high-risk populations., Results: NNNS evaluations were completed on 67 neonates with CHD, resulting in 97 evaluations (50 preoperative, 47 postoperative). Compared with normative values, the cohort with CHD demonstrated decreased attention, regulation, asymmetry, stress, arousal, and excitability, along with increased non-optimal reflexes, lethargy, and need for handling (p<0.05 for all). Additional clinical factors had a minimal effect on the neurobehavioral pattern. Compared with previously published patterns in high-risk neonates without CHD, the cohort with CHD demonstrated a unique pattern of behavior., Interpretation: Neonates with CHD demonstrate different neurobehavioral performance compared with typically developing neonates born at term as well as other high-risk neonates. Our experience suggests there is a unique neonatal neurobehavioral pattern in the hospitalized population with CHD. Targeted neonatal neurobehavioral evaluations may be useful in developing specific therapies to improve neurodevelopmental outcomes in neonates with CHD., What This Paper Adds: Neonates with congenital heart disease demonstrate different neurobehavioral performance than typically developing neonates. Evaluation of neonatal neurobehavioral performance provides an opportunity to identify neurodevelopmental variability early. Identification of neurobehavioral performance variability allows targeted interactions and therapy., (© 2018 Mac Keith Press.)

Background: Successful ageing with diabetes is challenged by co-morbidities, which may present barriers to self-care. Currently, measurement of physical and cognitive status is not part of routine care of the older person with diabetes, and these are not taken into account when devising the treatment plan., Objective: To describe a novel approach that integrates cognitive and physical assessment into the routine evaluation of the older person with diabetes and the tailor-made treatment plan devised accordingly. To provide estimates of the relative contribution of cognitive and physical disabilities in this population., Methods: Cognitive and physical assessments were added to the standard evaluation. A composite measure of cognitive and of physical status categorizing each individual to intact, mild, or severe impairment was generated. In addition, all recommendations provided were categorized and tabulated., Results: Of 119 individuals, over the age of 60 with type 2 diabetes who were referred because of difficulties in managing their disease, 16% and 3% of individuals met the criteria for severe cognitive/physical impairment, respectively, and 42% and 21% met the criteria for mild cognitive/physical impairment; 72%, 12.5%, 61% received recommendations related to intensification of physical activity, cognitive treatment, change in pharmacological agents, respectively. 25% were referred for further emotional treatment., Conclusions: These data suggest that a substantial proportion of individuals with diabetes over the age of 60 may have cognitive/physical impairment. It highlights the importance of measuring these as part of the multidisciplinary evaluation and being able to provide a tailor made treatment plan., (© 2018 John Wiley & Sons, Ltd.)

Psychiatry is the only medical specialty that lacks clinically applicable biomarkers for objective evaluation of the existing pathology at a single-patient level. On the basis of an original translational equilibriometric method for evaluation of movement patterns, we have introduced in the everyday clinical practice of psychiatry an easy-to-perform computerized objective quantification of the individual locomotor behaviour during execution of the Unterberger stepping test. For the last 20 years, we have gradually collected a large database of more than 1000 schizophrenic patients, their relatives, and matched psychiatric, neurological, and healthy controls via cross-sectional and longitudinal investigations. Comparative analyses revealed transdiagnostic locomotor similarities among schizophrenic patients, high-risk schizotaxic individuals, and neurological patients with multiple sclerosis and cerebellar ataxia, thus suggesting common underlying brain mechanisms. In parallel, intradiagnostic dissimilarities were revealed, which allow to separate out subclinical locomotor subgroups within the diagnostic categories. Prototypical qualitative (dysmetric and ataxic) locomotor abnormalities in schizophrenic patients were differentiated from 2 atypical quantitative ones, manifested as either hypolocomotion or hyperlocomotion. Theoretical analyses suggested that these 3 subtypes of locomotor abnormalities could be conceived as objectively measurable biomarkers of 3 schizophrenic subgroups with dissimilar brain mechanisms, which require different treatment strategies. Analogies with the prominent role of locomotor measures in some well-known animal models of mental disorders advocate for a promising objective translational research in the so far over-subjective field of psychiatry. Distinctions among prototypical, atypical, and diagnostic biomarkers, as well as between neuromotor and psychomotor locomotor abnormalities, are discussed. Conclusions are drawn about the translational and clinical implications of the new approach and its future perspectives., (© 2018 John Wiley & Sons, Ltd.)

Objective: To investigate the use of a robotic assessment tool to quantify sensorimotor, visuospatial attention, and executive function impairments in individuals with traumatic brain injury (TBI)., Setting: Foothills Hospital (Calgary, Canada)., Participants: Twenty-three subjects with first-time TBI in the subacute to chronic phase participated in this study. Normative data were collected from 275 to 494 neurologically intact control subjects for each robotic task., Design: A prospective observational case series. Subjects with TBI completed brief clinical cognitive and motor assessments followed by robotic assessments of upper limb reaching, position sense, bimanual motor ability, attention, and visuospatial skills. Scores of subjects with TBI were compared with normative data., Main Measures: Robotic task performance was computed for each subject on each task, as well as performance on specific task parameters. Clinical assessments included the Montreal Cognitive Assessment, Fugl-Meyer upper extremity assessment, and Purdue Peg Board., Results: Subjects with TBI demonstrated a variety of deficits on robotic tasks. The proportion of TBI subjects who were significantly different from controls ranged from 36% (dominant arm reaching) to 60% (bimanual object hitting task)., Conclusion: Robotic measures allowed us to quantify a range of impairments specific to each subject, and offer an objective tool with which to examine these abilities after TBI.

Aim: Retrospective analysis of the neurodevelopment in the first two years of life in patients with severe congenital heart disease., Patients and Methods: Out of 89 patients with severe congenital heart disease 19 were excluded due to a history of prematurity and/or chromosomopathy, four due to a history of ischemic stroke and two due to lack of medical history. Denver Test (DT) results at 2, 6, 12, 15 and 18 months, and results in motor, language and social interaction fields were achieved., Results: 59.4% were male and 40.6% female. The mean age of patients undergoing extracorporeal membrane oxygenation with pathological DT at 18 months was 3 months, compared to 11.88 months in those with normal DT. DT at 2 months was normal in 98.4% of patients, 87.5% at 6 and 12 months, 81.3% at 15 months and 85% at 18 months. Two patients with abnormal neurodevelopment normalized the DT before 24 months. The field of neurodevelopment most affected was language (15.6%), followed by motor (10.9%) and social interaction (8%)., Conclusions: Psychomotor development delay, especially in the area of language, is more frequent in patients with severe congenital heart disease. The presence of cyanosis and the need for extracorporeal membrane oxygenation were the variables that are most associated with this type of pathology.

Aims: This prospective study aimed to evaluate the relationship between persistently elevated lactate values in the arterial blood of newborns with grade II and III hypoxic ischemic encephalopathy (treated with therapeutic hypothermia) and psychomotor development at 24 months., Methods: 51 neonates of gestational age from 36 to 41 weeks receiving therapeutic hypothermia for moderate to severe hypoxic ischaemic encephalopathy had arterial blood lactate levels regularly analysed. At 24 months the infants' psychomotor development was evaluated and they were divided into two groups - those where the outcome was favourable (i.e. normal psychomotor development) and adverse (severe motor or sensory impairment or death). The lactate dynamics over time were retrospectively evaluated from the data collected, with the normal upper limit set at 4 mmol/L., Results: Of the 51 affected neonates, 7 died over the course of the study. 34 of the remaining 44 infants demonstrated normal psychomotor findings at 2 years old, with adverse findings in 10 cases. Although both groups experienced significant reductions in lactate over time, there were statistically significant differences between them regarding currently measured lactate levels., Conclusion: Absolute lactate values and their development over time can be a used as an auxiliary factor in making early estimates of the long-term outcome for newborns with neonatal asphyxia being treated with therapeutic hypothermia.

Neonatal diabetes mellitus is a rare form of monogenic diabetes which is diagnosed in the first six months of life. Here we report three patients with neonatal diabetes; two with isolated pancreas agenesis due to mutations in the pancreas-specific transcription factor 1A (PTF1A) enhancer and one with developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome, due to a KCNJ11 mutation. The two cases with mutations in the distal enhancer of PTF1A had a homozygous g.23508363A>G and a homozygous g.23508437A>G mutation respectively. Previous functional analyses showed that these mutations can decrease expression of PTF1A which is involved in pancreas development. Both patients were born small for gestational age to consanguineous parents. Both were treated with insulin and pancreatic enzymes. One of these patients’ fathers was also homozygous for the PTF1A mutation, whilst his partner and the parents of the other patient were heterozygous carriers. In the case with DEND sydrome, a previosly reported heterozygous KCNJ11 mutation, p.Cys166Tyr (c.497G>A), was identified. This patient was born to nonconsanguineous parents with normal birth weight. The majority of neonatal diabetes patients with KCNJ11 mutations will respond to sulphonylurea treatment. Therefore Glibenclamide, an oral antidiabetic of the sulphonylurea group, was started. This treatment regimen relatively improved blood glucose levels and neurological symptoms in the short term. Because we could not follow the patient in the long term, we are not able to draw conclusions about the efficacy of the treatment. Although neonatal diabetes mellitus can be diagnosed clinically, genetic analysis is important since it is a guide for the treatment and for prognosis.

Rationale: Reversible splenial lesion syndrome (RESLES) is a reversible condition with an excellent prognosis in most patients. The clinical features include altered states of consciousness, delirium, headache, and seizures, but no callosal disconnection syndromes have been described in RESLES., Patient Concerns: We presented a 57-year-old patient with alien hand syndrome, autotopagnosia, gait disorders, and left ideomotor apraxia after blood transfusion. The brain magnetic resonance imaging (MRI) showed a few regions with high signal intensity in the genu, body, and splenium of the right corpus callosum on diffusion weighted images. Cerebrovascular examination was unremarkable., Diagnoses: He was diagnosed with RESLES and callosal disconnection syndrome., Interventions: The patient received symptomatic and supportive treatment in our hospital., Outcomes: He recovered to baseline on following up of 6 months and abnormalities on brain MRI completely disappeared., Lessons: Neurologists should be aware of the symptoms of callosal disconnection syndrome in RESLES. In addition, caution should be taken when transfusing blood products in patients with gastrointestinal bleeding.

A boy was admitted at the age of 17 months. He had psychomotor retardation in early infancy. Physical examination revealed microcephalus, unusual facies, and a single palmar crease on his right hand, as well as muscle hypotonia in the extremities and hyperextension of the bilateral shoulder and hip joints. Genetic detection identified two pathogenic compound heterozygous mutations, c.8868-1G>A (splicing) and c.11624&#95;11625del (p.V3875Afs*10), in the VPS13B gene, and thus the boy was diagnosed with Cohen syndrome. Cohen syndrome is a rare autosomal recessive disorder caused by the VPS13B gene mutations and has complex clinical manifestations. Its clinical features include microcephalus, unusual facies, neutropenia, and joint hyperextension. VPS13B gene detection helps to make a confirmed diagnosis.

The aim of the study was to study visual acuity, visual perceptual, and VMI skills in patients after HSCT in childhood. Tests of visual perceptual skills, VMI, and visual acuity were performed in 102 children/adolescents (age range 4.3-20.9 years). Mean time from HSCT to testing was 6.0 years (0.9-17.5 years). Visual acuity was median 1.0 decimal (range 0.16-1.6). Visual perceptual skills (memory, form constancy, visual sequential memory) and VMI were low compared to age-equivalent normative data with, respectively, 36%, 45%, 60%, and 46% of all patients performing below the 25 percentile. All patients performed significantly lower than the 50 percentile in the reference material in visual sequential memory, P < .001 (boys P < .001 and girls P < .05). All patients also performed significantly lower than the 50 percentile in VMI (P < .01) (boys P < .05). Pretransplant conditioning regimen did not affect outcome if the results were corrected for age at HSCT. Visual perceptual skill problems and VMI problems frequently occur in patients after HSCT in childhood. Age at HSCT and original diagnosis influence the outcome. Neuropsychological assessment including visual perception is recommended in children after HSCT., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)