Minor Neurological Dysfunction Research Articles

Minor Neurological Dysfunction: A Comparative Study in Pediatrics with Different Types of Focal Epilepsy

AbstractEpilepsy is a disorder that occurs as a result of abnormal neuronal discharges in the brain and affects approximately 1% of children. Sensorimotor function impairments that are related to minor neurological deficits may be seen even in children diagnosed with epilepsy solely. This study aims to determine the type and areas of minor neurological dysfunction (MND) in children with Self-Limited Focal Epilepsy (SeLFE) and to compare the children with Self-Limited Epilepsy with Centrotemporal Spikes (SeLECTS) and SeLFE without SeLECTS. Fifty-six children diagnosed with epilepsy (28 SeLECTS and 28 SeLFE without SeLECTS) were included in the study. Both groups consisted of 13 girls and 15 boys. The mean ages of SeLECTS and SeLFE without SeLECTS groups were 9.68 ± 1.63 and 9.32 ± 1.62, respectively. A Modified Touwen Neurological Examination was performed to determine the type and areas of MND. There were no differences between the groups regarding MND type, coordination, fine manipulation, sensory, and involuntary movement areas (p > 0.05). It should be considered that children with SeLECTS may be neurologically affected as much as children with other types of epilepsy. Long-term problems due to epilepsy may be minimized by short-term neurodevelopmental follow-ups.

Children Newly Diagnosed with Fetal and Neonatal Alloimmune Thrombocytopenia: Neurodevelopmental Outcome at School Age

To evaluate the neurodevelopmental outcome at school age in children newly diagnosed with fetal neonatal alloimmune thrombocytopenia (FNAIT). This observational cohort study included children diagnosed with FNAIT between 2002 and 2014. Children were invited for cognitive and neurological testing. Behavioral questionnaires and school performance results were obtained. A composite outcome of neurodevelopmental impairment (NDI) was used, defined and subdivided into mild-to- moderate and severe NDI. Primary outcome was severe NDI, defined as IQ < 70, cerebral palsy with Gross Motor Functioning Classification Scale (GMFCS) level ≥ III, or severe visual/hearing impairment. Mild-to-moderate NDI was defined as IQ 70-85, minor neurological dysfunction or cerebral palsy GMFCS level ≤ II or mild visual/hearing impairment. In total, 44 children were included at a median age of 12 years (range 6-17 years). Neuroimaging at diagnosis was available in 82% (36/44) of children. High-grade intracranial hemorrhage (ICH) was detected in 14% (5/36). Severe NDI was detected in 7% (3/44); two children had high-grade ICH and one low-grade ICH and perinatal asphyxia. Mild-to- moderate NDI was detected in 25% (11/44); one child had high-grade ICH and eight were without ICH, yet for two children neuroimaging was not performed. Adverse outcome (perinatal death or NDI) was 39% (19/49). Four children (9%) attended special needs education, three of whom had severe NDI and one with mild-to-moderate NDI. Total behavioral problems within the clinical range were reported in 12%, which is comparable with 10% in the general Dutch population. Children who are newly diagnosed with FNAIT are at increased risk for long- term neurodevelopmental problems, even those without ICH.

Extremely preterm children and relationships of minor neurodevelopmental impairments at 6 years.

This study investigated minor impairments in neurological, sensorimotor, and neuropsychological functioning in extremely preterm-born (EPT) children compared to term-born children. The aim was to explore the most affected domains and to visualize their co-occurrences in relationship maps. A prospective cohort of 56 EPT children (35 boys) and 37 term-born controls (19 boys) were assessed at a median age of 6 years 7 months with Touwen Neurological Examination, Movement Assessment Battery for Children, 2nd edition (MABC-2), Sensory Integration and Praxis Test (SIPT), and a Developmental Neuropsychological Assessment, 2nd edition (NEPSY-II). Altogether 20 test domains were used to illustrate the frequency of impaired test performances with a bar chart profile and to construct relationship maps of co-occurring impairments. The EPT children were more likely to perform inferiorly compared to the term-born controls across all assessments, with a wider variance and more co-occurring impairments. When aggregating all impaired test domains, 45% of the EPT children had more impaired domains than any term-born child (more than five domains, p < 0.001). Relationship maps showed that minor neurological dysfunction (MND), NEPSY-II design copying, and SIPT finger identification constituted the most prominent relationship of co-occurring impairments in both groups. However, it was ten times more likely in the EPT group. Another relationship of co-occurring MND, impairment in NEPSY-II design copying, and NEPSY-II imitation of hand positions was present in the EPT group only. Multiple minor impairments accumulate among EPT children at six years, suggesting that EPT children and their families may need support and timely multi-professional interventions throughout infancy and childhood.

Long-term effects of selective fetal growth restriction (LEMON): a cohort study of neurodevelopmental outcome in growth discordant identical twins in the Netherlands

Singletons born after fetal growth restriction (FGR) are at increased risk of poor neurodevelopmental outcomes. Studies of singletons with FGR usually compare outcomes with those without FGR, a comparison that is inherently biased by obstetrical, parental, and genetic factors. We aim to compare neurodevelopmental outcomes between the smaller and larger twin in a population of discordant identical twins who shared a single placenta (monochorionic diamniotic), naturally eliminating these confounders. This study is part of the cohort study LEMON of monochorionic diamniotic twins with selective FGR. All monochorionic diamniotic twins with selective FGR who were born in Leiden University Medical Center (Leiden, Netherlands) between March 1, 2002, and Dec 31, 2017, were eligible for inclusion. Twin pregnancies that were complicated by twin-twin transfusion syndrome, twin anaemia polycythaemia sequence, or monoamnionicity were excluded. Cognitive performance was evaluated with two standardised psychometric age-appropriate tests, producing a full-scale intelligence quotient (FSIQ). Motor functioning was assessed with a standardised neurological examination. A composite outcome of neurodevelopmental impairment (NDI) was used, subdivided into mild NDI (defined as FSIQ <85, minor neurological dysfunction or cerebral palsy grade 1, or mild visual or hearing impairment) and severe NDI (defined as FSIQ <70, severe neurological dysfunction, or severe visual or hearing impairment). Between Jan 25, 2021, and March 15, 2022, 47 twin pairs were enrolled in the study and underwent neurodevelopmental assessment. The median gestational age at birth was 33·9 weeks (IQR 31·3-36·0) for the 47 included twin pairs, with median birthweights of 1400 g (1111-1875) in the smaller twin and 2003 g (1600-2680) in the larger twin. The median age at neurodevelopmental assessment was 11 years (8-13). Median FSIQ was 94 (86-101) for the smaller twin and 100 (92-108) for the larger twin (p<0·0001). More smaller twins had mild NDI (17 [36%] of 47) than did the larger twins (five [11%] of 47; odds ratio 4·8 [95% CI 1·6-14·1]; p=0·0049). There was no difference in the proportion of children with severe NDI (two [4%] of 47 in both groups, p=1·0). As mild NDI can impede children in their daily functioning, we recommend standardised long-term follow-up, including neurodevelopmental testing, for monochorionic diamniotic twins with selective FGR to facilitate early identification of children at risk. The Dutch Heart Foundation.

Long-term neurodevelopmental outcome in children after antenatal intravenous immune globulin treatment in fetal and neonatal alloimmune thrombocytopenia

Children with fetal and neonatal alloimmune thrombocytopenia face increased risk of intracranial hemorrhage potentially leading to developmental impairment. To prevent intracranial hemorrhage, pregnant women with alloantibodies against fetal platelets are often treated with intravenous immunoglobulin. Intravenous immunoglobulin seems effective in vastly reducing the risk of fetal or neonatal bleeding complications. However, information on long-term neurodevelopment of these children is lacking. This study aimed to evaluate long-term neurodevelopmental outcome in children with fetal and neonatal alloimmune thrombocytopenia who were treated with intravenous immunoglobulin antenatally. An observational cohort study was performed, including children of mothers treated with intravenous immunoglobulin during pregnancy because a previous child was diagnosed with fetal and neonatal alloimmune thrombocytopenia. Children were invited for a follow-up assessment including standardized cognitive and neurologic tests. The parents were asked to complete a behavioral questionnaire and school performance reports. The primary outcome was severe neurodevelopmental impairment, defined as severe cognitive impairment (intelligence quotient <70), cerebral palsy with Gross Motor Function Classification System Level ≥3, bilateral blindness, and/or bilateral deafness (requiring amplification). The secondary outcome was mild to moderate neurodevelopmental impairment, defined as either mild to moderate cognitive impairment (intelligence quotient <85), cerebral palsy with Gross Motor Function Classification System Level ≤2, minor neurologic dysfunction, vision loss, and/or hearing loss. Between 2003 and 2017, 51 children were live-born after antenatal intravenous immunoglobulin treatment. One family moved abroad and was therefore not eligible for inclusion. In total, 82% (41/50) of the eligible cases were included for neurodevelopmental assessment at a median age of 9 years and 8 months. Severe neurodevelopmental impairment was not detected. The incidence of mild to moderate neurodevelopmental impairment was 14% (6/41; 95% confidence interval, 6%-29%). The children's mean cognitive score, behavioral scores, and academic achievement were not different from those observed in the Dutch norm groups. Neuroimaging was performed in 90% (37/41) of cases. Severe intracranial hemorrhage was diagnosed in 2 cases (5%), one antenatally before the start of intravenous immunoglobulin and the other case 1 day after birth. Both cases had a normal neurodevelopmental outcome. The risk of neurodevelopmental impairment in children whose mothers were treated for fetal and neonatal alloimmune thrombocytopenia with antenatal intravenous immunoglobulin is comparable to that reported in the general population.

Изучение способности детей 3–5 лет формировать понятия разной степени сложности в возрастном и неврологическом аспектах

The ability to identify common features of objects and relationships among them and to perceive relative similarities in different situations allow children to quickly learn new material. The development of these skills in preschool age is not fully understood. In particular, the abilities to form relative concepts based on one or several features of objects and ability to act by analogy have not been studied in 3–5-year-old children. Furthermore, the influence of mild neurological disorders on building these abilities has not been studied properly either. The goal of this research was to study the ability of 3–5-year-old children to independently form empirical concepts based on relations among objects and to evaluate the effects of the following factors: (1) the number of features (one/two features); (2) the age of the child (3–4 vs. 4–5 years); (3) the neurological profile of the participants. The number of features that had to be taken into account to successfully identify relationships between objects was found to have a significant effect on the speed of concept production and the ability to judge by analogy. Indeed, 3–5-year-old children found concepts based on two features more difficult compared to those based on one feature. A standardised neurological examination was used to divide the participants of the study into groups with a 3:2:1 ratio according to the severity of their minor neurological dysfunction (MND): those without MND, MND-1 and MND-2. When analysing the time it takes children to form concepts and the ability to act by analogy, no difference was observed in different age groups within the 3–5 range (3–4 vs. 4–5). It was, however, observed that the extent of MND has an impact on the ability to form complex two-feature concepts. Thus, the study of cognitive functions at the age of 3–5 years, together with a detailed standardised neurological examination, makes it possible to predict potential cognitive and behavioural deviations at an older age.

Neonatal hypoxic-ischaemic encephalopathy: Motor impairment beyond cerebral palsy

Research investigating neuromotor function in the absence of cerebral palsy (CP) for children who had neonatal HIE is limited.To investigate school-age neurological and neuromotor function, and correlations with attention, neonatal Magnetic Resonance Imaging (MRI), and neuromotor assessments at toddler age.Twenty-seven children with neonatal HIE without CP who underwent hypothermia treatment and a comparison group of 20 children were assessed at age 5-7 years for Minor Neurological Dysfunction (MND; simplified Touwen), motor skills (Movement Assessment Battery for Children-2; MABC-2), parental concern over motor function (MABC Checklist), general cognition (Wechsler Preschool and Primary Scale of Intelligence-IV, WPPSI), and attention (DuPaul ADHD Rating Scale). Neurological examination and motor development, using Bayley-3 scales, at age 24-months was extracted from the clinical database. Clinical neonatal MRI was assessed for hypoxic-ischaemic injury.In the HIE group, MND was more prevalent (p = 0.026) and M-ABC performance (total score p = 0.006; balance subtest p = 0.008) was worse; parents were more concerned about children's motor function (p = 0.011). HIE group inattention scores were higher (p = 0.032), which correlated with lower MABC-2 scores (rs = -0.590, p = 0.004). Neurological examination at 24-months correlated with MND (rs = 0.437, p = 0.033); Bayley-3 motor scores did not correlate with M-ABC-2 scores (rs = 368, p = 0.133). Neonatal MRI findings were not associated with school-age MND (rs = 0.140, p = 0.523) or MABC-2 (rs = 0.300, p = 0.165).Children with neonatal HIE, without CP, treated with hypothermia may be more likely to develop MND and motor difficulties than typically developing peers. Inattention may contribute to motor performance. In the absence of CP, neonatal MRI and toddler age assessment of motor development have limited predictive value for school-age outcome. Since this was an exploratory study with a small sample size, findings should be confirmed by a definite larger study.

Cognitive and neurological outcome of patients in the Dutch pyridoxine-dependent epilepsy (PDE-ALDH7A1) cohort, a cross-sectional study.

Pyridoxine monotherapy in PDE-ALDH7A1 often results in adequate seizure control, but neurodevelopmental outcome varies. Detailed long-term neurological outcome is unknown. Here we present the cognitive and neurological features of the Dutch PDE-ALDH7A1 cohort. Neurological outcome was assessed in 24 patients (age 1-26 years); classified as normal, complex minor neurological dysfunction (complex MND) or abnormal. Intelligence quotient (IQ) was derived from standardized IQ tests with five severity levels of intellectual disability (ID). MRI's and treatments were assessed. Ten patients (42%) showed unremarkable neurological examination, 11 (46%) complex MND, and 3 (12%) cerebral palsy (CP). Minor coordination problems were identified in 17 (71%), fine motor disability in 11 (46%), posture/muscle tone deviancies in 11 (46%) and abnormal reflexes in 8 (33%). Six patients (25%) had an IQ>85, 7 (29%) borderline, 7 (29%) mild, 3 (13%) moderate, and 1 severe ID. Cerebral ventriculomegaly on MRI was progressive in 11. Three patients showed normal neurologic exam, IQ, and MRI. Eleven patients were treated with pyridoxine only and 13 by additional lysine reduction therapy (LRT). LRT started at age <3 years demonstrated beneficial effect on IQ results in 3 patients. Complex MND and CP occurred more frequently in PDE-ALDH7A1 (46% and 12%) than in general population (7% and 0.2%, Peters et al., 2011, Schaefer et al., 2008). Twenty-five percent had a normal IQ. Although LRT shows potential to improve outcomes, data are heterogeneous in small patient numbers. More research with longer follow-up via the International PDE Registry (www.pdeonline.org) is needed.

Hammersmith Infant Neurological Examination and long-term cognitive outcome in children born very preterm.

To study the association between the Hammersmith Infant Neurological Examination (HINE) at age 2years and neurocognition at age 11years in children born very preterm. We hypothesized that the HINE at 2years would be associated with neurocognition, that is, neurological, motor, and cognitive outcomes at 11years. A total of 174 children (mean gestational age 29.0wks, SD 2.7; minimum 23.0, maximum 35.9; 95 [55%] males, 79 [45%] females) born very preterm (birthweight ≤1500g/gestational age <32wks), were included in a prospective cohort recruited from 2001 to 2006 in Turku, Finland. The HINE was performed at 2years' corrected age. Neurocognition at 11years was assessed with the Touwen neurological examination, Movement Assessment Battery for Children, Second Edition (MABC-2), and full-scale IQ (Wechsler Intelligence Scale for Children, Fourth Edition). The HINE global score was associated with the results of the Touwen neurological examination (odds ratio [OR]=0.9, 95% confidence interval [CI] 0.8-0.9, p=0.001), MABC-2 (β=1.4, 95% CI 0.7-2.2, p<0.001), and full-scale IQ (β=1.2, 95% CI 0.8-1.7, p<0.001), even when adjusted. When children with cerebral palsy (CP) were excluded, the HINE was still associated with full-scale IQ (unadjusted β=1.2, 95% CI 0.3-2.1, p=0.01). A higher HINE global score at 2 years was associated with better general intelligence at 11 years even in children without CP. The HINE may be a useful tool to detect children at risk for later cognitive impairment. What this paper adds A Hammersmith Infant Neurological Examination (HINE) global score at 2years was associated with long-term neurocognitive function. Severe cognitive impairment was significantly more common in 11-year-old children with complex minor neurological dysfunction compared to typically developing children. The HINE performed at 2years detects risks of cognitive impairment at 11years in children born very preterm. A higher HINE score at 2years was associated with better general intelligence at 11years.

Neurological and Cognitive Performance After Childhood Encephalitis.

Background: Children with encephalitis have increased risk for long-term neurological sequelae. We investigated minor neurological dysfunction (MND) and cognitive performance as a measurement for long-term outcome of encephalitis in childhood.Materials and Methods: Children with encephalitis (n = 98) treated in Turku University Hospital during the years 1995–2016 were retrospectively identified. We included the patients without severe developmental delay before the encephalitis and without recorded neurological disability caused by encephalitis. MND was assessed using the Touwen examination. Age-appropriate Wechsler Intelligence Scale was used to determine the full-scale intelligence quotient (IQ). Residual symptoms in everyday life were evaluated using a questionnaire.Results: Forty-two subjects participated in the study and returned the questionnaire regarding residual symptoms. The median age was 4.3 years at the time of encephalitis, and 11.3 years at the time of the Touwen examination (n = 41) and the cognitive assessment (n = 38). The Touwen examination indicated MND in 29 of 41 participants (71%; simple MND in 16 and complex MND in 13 patients). The median full-scale IQ was lower in participants with MND compared with participants without MND (98 vs. 110, p = 0.02). Participants with IQ < 85 (n = 5) had lower median age at acute encephalitis compared to participants with IQ ≥ 85 (n = 33) (1.8 vs. 5.3 years, p = 0.03). Problems in daily performance were reported in participant with MND (p = 0.2) and low full-scale IQ (p = 0.008).Conclusions: The prevalence of MND was high and it was related to lower cognitive performance after childhood encephalitis. Younger age at acute encephalitis was a risk factor for lower cognitive performance.

Developmental parameters and physical fitness in preschool children with Minor Neurological Dysfunction.

The preschool years constitute a critical period during which significant changes are experienced in the acquisition of locomotor skills due to maturation of the nervous system. Our aim was to investigate the developmental parameters and physical fitness in preschool children with Minor Neurological Dysfunction (MND). The study was carried out in 212 preschool children without any known health problems. Sociodemographic characteristics of children were recorded. Denver Developmental Screening Test (DDST) II, Touwen Neurological Examination, and Preschool Physical Fitness (PREFIT) test battery were used to assess developmental parameters, neurological status, and physical fitness, respectively. There was a statistical difference in the physical fitness and developmental parameters in preschool children with MND compared with healthy peers (p < 0.05). There was also a relationship between physical fitness and developmental parameters (p < 0.05). Early identification of problems in developmental parameters and physical fitness in preschool children with MND might help to implement early supportive physiotherapy and rehabilitation.

Analysis of neurodevelopmental outcomes of preadolescents born with extremely low weight revealed impairments in multiple developmental domains despite absence of cognitive impairment.

Background and aimsChildren with extremely low‐birth weight (ELBW) have a high risk for cognitive, motor, and attention impairments and learning disabilities. Longitudinal follow‐up studies to a later age are needed in order to increase understanding of the changes in neurodevelopmental trajectories in targeting timely intervention. The aims of this study were to investigate cognitive and motor outcomes, attention‐deficit hyperactivity (ADHD) behaviour, school performance, and overall outcomes in a national cohort of ELBW children at preadolescence, and minor neuromotor impairments in a subpopulation of these children and to compare the results with those of full‐term controls. The additional aim was to report the overall outcome in all ELBW infants born at 22 to 26 gestational weeks.MethodsThis longitudinal prospective national cohort study included all surviving ELBW (birth weight <1000 g) children born in Finland in 1996 to 1997. No children were excluded from the study. Perinatal, neonatal, and follow‐up data up to the age of 5 years of these children were registered in the national birth register. According to birth register, the study population included all infants born at the age under 27 gestational weeks. At 11 years of age general cognitive ability was tested with the Wechsler Intelligence Scale for Children, ADHD behavior evaluated with a report from each child's own teacher (ADHD Rating Scale IV), and school performance with a parental questionnaire. An ELBW subpopulation consisting of a cohort representative children from the two university hospitals from two regions (n = 63) and the age‐matched full‐term born controls born in Helsinki university hospital (n = 30) underwent Movement Assessment Battery for Children and Touwen neurological examination comprising developmental coordination disorder (DCD) and minor neurological dysfunction (MND), respectively.ResultsOf 206 ELBW survivors 122 (73% of eligible) children and 30 (100%) full‐term control children participated in assessments. ELBW children had lower full‐scale intellectual quotient than controls (t‐test, 90 vs 112, P < .001), elevated teacher‐ reported inattention scores (median = 4.0 vs 1.0, P = .021, r = .20) and needed more educational support (47% vs 17%, OR 4.5, 95% CI 1.6‐12.4, P = .02). In the subpopulation, the incidences of DCD were 30% in ELBW and 7% in control children (P = .012, OR 6.0 CI 1.3‐27.9), and complex MND 12.5% and 0%, (P = .052; RR 1.1 95% CI 1.04‐1.25), respectively. Of survivors born in 24 to 26 gestational weeks, 29% had normal outcome.ConclusionAs the majority of the extremely preterm born children had some problems, long‐term follow‐up is warranted to identify those with special needs and to design individual multidisciplinary support programs.

A Preliminary Study on Cranio-Facial Characteristics Associated with Minor Neurological Dysfunctions (MNDs) in Children with Autism Spectrum Disorders (ASD).

Background. Craniofacial anomalies and minor neurological dysfunction (MNDs) have been identified, in literature, as risk factors for neurodevelopmental disorders. They represent physical indicators of embryonic development suggesting a possible contributory role of complications during early, even pre-conceptional, phases of ontogeny in autism spectrum disorders (ASD). Limited research has been conducted about the co-occurrence of the two biomarkers in children with ASD. This study investigates the associative patterns of cranio-facial anomalies and MNDs in ASD children, and whether these neurodevelopmental markers correlate with intensity of ASD symptoms and overall functioning. Methods. Caucasian children with ASD (n = 33) were examined. Measures were based on five anthropometric cranio-facial indexes and a standardized and detailed neurological examination according to Touwen. Relationships between anthropometric z-scores, MNDs and participant characteristics (i.e., age, cognitive abilities, severity of autistic symptoms measured using the Childhood Autism Rating Scale (CARS) checklist) were assessed. Results. With respect to specific MNDs, significant positive correlations were found between Cephalic Index and Sensory deficits (p-value < 0.001), which did not correlate with CARS score. Importantly, CARS score was positively linked with Intercanthal Index (p-value < 0.001), and negatively associated with posture and muscle tone (p-value = 0.027) and Facial Index (p-value = 0.004). Conclusion. Our data show a link between a specific facial phenotype and anomalies in motor responses, suggesting early brain dysmaturation involving subcortical structures in cerebro-craniofacial development of autistic children. This research supports the concept of a “social brain functional morphology” in autism spectrum disorders.

Motor behaviour in infancy is associated with neurological, cognitive, and behavioural function of children born to parents with reduced fertility.

AimTo evaluate the associations between motor development in infancy and developmental outcomes at school age.MethodParticipants were 195 children (99 males, 96 females; mean age [SD] 9y 3mo [3mo], range 8y 4mo–10y 11mo) born to couples whose reduced fertility was or was not treated with assisted reproductive technologies. Motor behaviour was assessed at 4, 10, and 18 months with the Infant Motor Profile (IMP). IQ, neurological optimality score (NOS), and behavioural problem scores were measured at 9 years with the Wechsler Abbreviated Scale of Intelligence, minor neurological dysfunction assessment, and the Child Behavior Checklist respectively.ResultsChildren with a slow developmental trajectory in the IMP‐domain adaptability had an IQ 12.6 points lower (95% confidence interval [CI] 4.7–20.4) and an NOS 3.4 points lower (95% CI 0.7–6.2) at 9 years of age than children with typical adaptability development. Children with a slow developmental trajectory in the IMP‐domain performance had an IQ 5.0 points lower (95% CI 0.7–9.3) than children with typical performance development. A non‐optimal trajectory in IMP‐variation and a fluctuating trajectory in IMP‐fluency were associated with higher internalizing scores of 3.6 and 5.8 points respectively, than infants with optimal IMP‐domain trajectories.InterpretationIn relatively low‐risk children, motor behaviour in infancy was associated with neurological, cognitive, and behavioural function at school age.

Improved Accuracy of Saxitoxin Measurement Using an Optimized Enzyme-Linked Immunosorbent Assay.

Paralytic shellfish poisoning (PSP) is precipitated by a family of toxins produced by harmful algae, which are consumed by filter-feeding and commercially popular shellfish. The toxins, including saxitoxin, neosaxitoxin, and gonyautoxins, accumulate in shellfish and cause intoxication when consumed by humans and animals. Symptoms can range from minor neurological dysfunction to respiratory distress and death. There are over 40 different chemical congeners of saxitoxin and its analogs, many of which are toxic and many of which have low toxicity or are non-toxic. This makes accurate toxicity assessment difficult and complicates decisions regarding whether or not shellfish are safe to consume. In this study, we describe a new antibody-based bioassay that is able to detect toxic congeners (saxitoxin, neosaxitoxin, and gonyautoxins) with little cross-reactivity with the low or non-toxic congeners (decarbamoylated or di-sulfated forms). The anti-saxitoxin antibody used in this assay detects saxitoxin and neosaxitoxin, the two most toxic congers equally well, but not the relatively highly toxic gonyautoxins. By incorporating an incubation step with L-cysteine, it is possible to convert a majority of the gonyautoxins present to saxitoxin and neosaxitoxin, which are readily detected. The assay is, therefore, capable of detecting the most toxic PSP congeners found in commercially relevant shellfish. The assay was validated against samples whose toxicity was determined using standard HPLC methods and yielded a strong linear agreement between the methods, with R2 values of 0.94–0.96. As ELISAs are rapid, inexpensive, and easy-to-use, this new commercially available PSP ELISA represents an advance in technology allowing better safety management of the seafood supply and the ability to screen large numbers of samples that can occur when monitoring is increased substantially in response to toxic bloom events

Minor neurological dysfunction in preterm children and its association with school readiness

ABSTRACTMinor neurological dysfunction (MND) has been associated with learning, cognitive, and motor problems in preterm children. This study aims to study the prevalence of MND in preterm children without cerebral palsy in the preschool period and to investigate its association with school readiness. Forty-four children born at less than 37 weeks of gestation and 35 term children at a mean age of 5 years 6 months were included in the study. MND was classified according to Touwen. School readiness was assessed with the Marmara Primary School Readiness Scale. The prevalence of MND in preterm preschoolers was higher compared to their term-peers. Linear regression analyses showed that MND was the strongest predictor of school readiness in the preterm group. Preterm children, in the absence of CP, are at risk of MND and this is associated with school readiness. Greater emphasis needs to be placed on the follow-up, and an intervention should be prepared for preterm children with MND when they are starting school.

IVF procedures are not, but subfertility is associated with neurological condition of 9-year-old offspring

In vitro fertilization (IVF) is not associated with neurological abnormalities in offspring's early childhood. Yet, it is unclear whether this is also true for school age. Neither do we know the role of parental subfertility in offspring's neurological development. The present study examined neurological condition at 9 years of 57 singletons born after controlled ovarian hyperstimulation IVF (COH-IVF), 46 singletons born after modified natural cycle IVF (MNC-IVF) and 66 singletons born to subfertile parents after natural conception (Sub-NC). To assess the effect of subfertility, the groups were pooled to form a subfertile group, and compared with a prospectively followed fertile reference group (n = 282). The sensitive Minor Neurological Dysfunction (MND) examination was used, resulting in the detailed Neurological Optimality Score (NOS) and the prevalence of the clinically relevant complex MND. Neurological condition of the three subfertile groups did not differ significantly: median NOS was 53 in each subfertile group and the prevalence of complex MND in the three subfertile groups was 30%, 37% and 36%, respectively. However, the NOS was lower and the prevalence of complex MND higher in children born to subfertile couples than in children of fertile couples (adjusted mean difference [95% CI]: −4.48 [−5.53 to −3.42]) and adjusted OR [95% CI]: 5.13 [2.60–10.16], respectively). We conclude that ovarian hyperstimulation, in vitro procedures, and the combination of both were not associated with a less favourable neurological outcome of 9-year-old singletons. However, the presence of parental subfertility was associated with less favourable neurological outcome of offspring at 9 years follow up.

Minor neurological dysfunction and other comorbidities in children born extremely preterm.

This commentary is on the original article by Broström et al. on pages 826–832 of this issue.

Minor Neurological Dysfunctions (MNDs) in Autistic Children without Intellectual Disability.

Background: Children with autism spectrum disorder (ASD) require neurological evaluation to detect sensory-motor impairment. This will improve understanding of brain function in children with ASD, in terms of minor neurological dysfunctions (MNDs). Methods: We compared 32 ASD children without intellectual disability (IQ ≥ 70) with 32 healthy controls. A standardized and age-specific neurological examination according to Touwen was used to detect the presence of MNDs. Particular attention was paid to severity and type of MNDs. Results: Children with ASD had significantly higher rates of MNDs compared to controls (96.9% versus 15.6%): 81.3% had simple MNDs (p < 0.0001) and 15.6% had complex MNDs (p = 0.053). The prevalence of MNDs in the ASD group was significantly higher (p < 0.0001) than controls. With respect to specific types of MNDs, children with ASD showed a wide range of fine manipulative disability, sensory deficits and choreiform dyskinesia. We also found an excess of associated movements and anomalies in coordination and balance. Conclusions: Results replicate previous findings which found delays in sensory-motor behavior in ASD pointing towards a role for prenatal, natal and neonatal risk factors in the neurodevelopmental theory of autism.

Developmental dysgraphia is often associated with minor neurological dysfunction in children with developmental coordination disorder (DCD)

Children with developmental coordination disorder (DCD) are particularly affected by handwriting disorders, which remain poorly understood and are not clearly defined. The aim of our study is to provide a better understanding of handwriting disorders, and specifically of dysgraphia in children with DCD. Sixty-five children with DCD (5-15 years), enrolled according to DSM-5, were assessed with handwriting testing and standardized assessments of neuropsychological, neurovisual, MRI and neuropsychomotor functions, with special attention paid to muscular tone examination. While handwriting disorders were strongly represented in our sample of children with DCD (89%), dysgraphia appeared uncommon (17%) and was closely related to several specific dysfunctions of laterality establishment; mild pyramidal tract dysfunction with distal phasic stretch reflex (PSR) in lower limbs; digital praxis slowness (both P<0.05). In our sample, dysgraphia was closely related to minor neurological dysfunction (MND) suggesting a disturbance of motor control at the level of the corticospinal motor pathway. This highlights the uncommon character of dysgraphia in children with DCD for which diagnosis should be made through a particular attention to evaluation of MND with muscular tone examination. This consideration, both in the research setting and in clinical practice, appears necessary to avoid inaccurate clinical diagnosis and to optimize appropriate therapeutic management.