Intelligence and Executive Functions: A Comprehensive Assessment of Intellectually Gifted Children.

OBJECTIVE: Executive functions (EFs) play a key role in cognitive and behavioral functioning. Their multiple forms and implications for daily life behaviors mean they are sometimes equated with intelligence. Several elements even suggest that intellectually gifted children (IGC) may present better executive functioning than typical developing children (TDC, children with intelligence in the average range). However, no study has ever completely tested this hypothesis by a comprehensive assessment of EFs in IGC. METHOD: Results of 30 IGC and 35 TDC aged from 6 to 16 years old were compared through a comprehensive assessment of EFs (inhibition, flexibility, and planning), comprising performance-based and daily life measures. RESULTS: IGC did not differ from TDC in EF performance-based measures. However, they scored higher in parents' and some teachers' ratings, suggesting higher indicators of difficulties in daily life. CONCLUSIONS: Contrary to expectations, high intellectual level does not appear to be associated with superior EFs. Surprisingly, parents and teachers of IGC reported more complaints about their executive functioning in everyday life. We put forward different hypotheses to explain this contrast. Further research is needed to better understand this phenomenon, in which neuropsychology has a fundamental role to play.

Clinical characteristics of COVID-19 infection in polyhandicapped persons in France.

AIM: Little is known about the clinical profile of COVID-19 infection in polyhandicapped persons. This study aimed to describe the characteristics of this infection among individuals with polyhandicap. METHOD: This was a retrospective observational study. Polyhandicap was defined by the combination of motor deficiency, profound mental retardation, and age at onset of cerebral lesion younger than 6 years. A positive COVID-19 status was considered for patients with a positive COVID-19 laboratory test result, or patients presenting with compatible symptoms and living in an institution or at home with other patients or relatives who had laboratory-confirmed COVID-19 infection. Data collection included sociodemographic data, clinical and paraclinical characteristics, as well as the management and treatment for COVID-19 infection. RESULTS: We collected 98 cases, with a sex ratio of 0.98 and a mean age of 38.5 years (3 months to 73 years). COVID-19 infection was paucisymptomatic in 46% of patients, 20.6% of patients presented with dyspnea, while the most frequent extra-respiratory symptoms were digestive (26.5%) and neurological changes (24.5%); 18 patients required hospital admission, four adults died. The mean duration of infection was longer for adults than for children, and the proportion of taste and smell disorders was higher in older patients. CONCLUSION: These findings suggest that PLH persons often develop paucisymptomatic forms of COVID-19 infection, although they may also experience severe outcomes, including death. Clinicians should be aware that COVID-19 symptoms in PLH persons are often extra-respiratory signs, mostly digestive and neurologic, which may help in the earlier identification of COVID-19 infection in this particular population of patients.

Multidisciplinary approach and psychosocial management of spinal muscular atrophy (SMA).

Spinal Muscular Atrophy (SMA) is a severe complex disorder involving different aspects of care and professionals. Helping individuals to achieve their best possible quality of life is an essential part of health care. A multidisciplinary approach to management across the range of actors improves the function, quality of life and longevity of patients with SMA. Multidisciplinary management should be designed to address the psychosocial challenges of patients with prolonged survival and novel therapies. In this part, we focus on multidisciplinary management of SMA, pluridisciplinary consultations, emergency management, psychosocial care and transitions to adulthood. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

[Pain in children with neurological impairment: A review from the French Pediatric Neurology Society]. / La douleur chez l'enfant en situation de handicap neurologique : mise au point de la Commission « déficience intellectuelle et handicap ¼ de la Société française de neurologie pédiatrique.

Management of pain is one of the major expectations of children with neurological impairment and their families. The medical literature is poor on this topic accounting for approximately 0.15 % of the publications on pain in general. The objective of the French Pediatric Neurology Society was to review the current knowledge on this topic. Bibliographic research was conducted with PubMed and RefDoc for publications between 1994 and 2014 in French or English. A total of 925 articles were retrieved and 92 were selected for review. Pain is common in this population: a 2-week survey indicated that pain occurs in 50-75 % of children. Pain negatively impacts the quality of life of children and their parents. Children with neurological impairment express their pain with pain expression patterns and specific patterns common to children (change of tone, abnormal movements, spasticity, paradoxical reactions, such as laughter, self-injury or vasomotor dysfunction). Some children with neurological impairment are able to use self-report pain scales. If not, observational measures should be used. Behavioral rating scales specifically designed for this population are more sensitive than others. Scales must be selected according to children's communication skills, type of pain, and the context. Sometimes behavioral changes are the only expression of pain: any change in sleep, tone, feeding, or mood must suggest pain in this population. Management of pain remains difficult. There are no specific guidelines. Procedural pain management guidelines and the usual analgesic drugs can be used in children with neurological impairment with specific concerns regarding tolerance and side effects. These children are particularly at risk for neuropathic pain. A multidisciplinary approach is helpful, involving physicians, nurses, physiotherapists, psychologists and parents.

[Multicentric study of medical care and practices in spinal muscular atrophy type 1 over two 10-year periods]. / Amyotrophie spinale type 1 : enquête multicentrique des pratiques de soins et d'accompagnement palliatif sur deux périodes successives de 10ans.

AIM: Questions about care practices and the role of palliative care in pediatric neurodegenerative diseases have led the Neuromuscular Committee of the French Society of Neurology to conduct a retrospective study in spinal muscular atrophy type 1, a genetic disease most often leading to death before the age of 1 year. MATERIAL AND METHODS: A retrospective multicenter study from pediatricians included in the reference centers of pediatric neuromuscular diseases was carried out on two 10-year periods (1989-1998 and 1999-2009). RESULTS: The 1989-1998 period included 12 centers with 106 patients, the 1999-2009 period 13 centers with 116 children. The mean age of onset of clinical signs was 2.1 months (range, 0-5.5 months), the median age at diagnosis was 4 months (range, 0-9 months) vs 3 months. The median age of death was 7.5 months (range, 0-24 months) vs 6 months. The care modalities included physiotherapy (90 %), motor support (61 % vs 26 % for the previous period), enteral nutrition by nasogastric tube (52 % vs 24 %), and 3.4 % of children had a gastrostomy (vs 1.8 %). At home, pharyngeal aspiration was used in 64 % (vs 41 %), oxygen therapy in 8 %, noninvasive ventilatory support in 7 %. The mean age at death was 8.1 months (range, 0-24 months) vs 7 months, the time from diagnosis to death was 4 months vs 3 months. Death occurred at home in 23 % vs 17 %, in a pediatric unit in 62 % vs 41 %. The use of analgesics and sedative drugs was reported in 60 % of cases: 40 % morphine (vs 18 %) and benzodiazepines in 48 % (vs 29 %). Respiratory support was limited mostly to oxygen by nasal tube (55 % vs 54 %), noninvasive ventilation in 9 % of the cases, and intubation and assisted mechanical ventilation (2 %). DISCUSSION AND CONCLUSION: These results confirm a change in practices and the development of palliative care in children with a French consensus of practices quite different from the standard care in North-America and closer to the thinking of English medical teams. A prospective study within the 2011 national hospital clinical research program (PHRC 2011) is beginning in order to evaluate practices and the role of families and caregivers.

A survey of medical and paramedical involvement in children with cerebral palsy in Britanny: preliminary results.

AIM: To describe the amount of medical and paramedical involvement in a sample of Breton children with cerebral palsy as a function of the Gross Motor Function Classification System (GMFCS). MATERIALS AND METHODS: This is a transversal descriptive study. All children with cerebral palsy in Brittany were eligible. Parents who accepted to participate were asked to fill in a questionnaire regarding medical and paramedical involvement with their child. RESULTS: One hundred and thirty-three parents participated. 40.6% of the children were level I on the GMFCS, 20.3% II, 12.03% III, 13.53% IV and 13.53% were level V. Thirty-nine percent of the children took at least one medication (of which 43% were antiepileptic drugs). 33.1% of the children had received at least one injection of botulinum toxin within the year. Forty-four percent used a mobility aid. Eighty-five percent of the children had at least one orthotic device, most often a night ankle-foot orthosis. The median number of rehabilitation sessions per week was 3.85 [0.5-11.5]. The frequency and type of sessions were mostly related to the GMFCS level. CONCLUSION: This study reports high levels of medical and paramedical involvement. Studies must attempt to define optimal practice.

Effectiveness of nitrous oxide and analgesic cream (lidocaine and prilocaine) for prevention of pain during intramuscular botulinum toxin injections in children.

AIMS: To evaluate the effectiveness of an analgesic protocol with nitrous oxide and anaesthetic cream (lidocaine and prilocaine, EMLA) for children undergoing botulinum toxin injections. PATIENTS AND METHODS: Prospective study including 51 injection sessions, 34 children with a mean age of 5.94 (range 2-15) and 209 injected muscles. Pain was evaluated with the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), the Visual Analogue Scale (VAS) and the Face Pain Scale (FPS) for the children and with a VAS for the parents. RESULTS: CHEOPS score for the 51 sessions was 8.50 (S.D. 3.56). Forty-nine percent of scores were above the therapeutic threshold of 9; 25% of the children evaluated the pain above the therapeutic threshold of 3; 44.74% of the parents' estimations exceeded 3. No correlation was found between age, weight, number of injected muscle and CHEOPS score. CONCLUSION: The association of MEOPA and anaesthetic cream is only effective for 50% of children. This is much lower than treatments for other types of acute induced pain in children. Botulinum toxin injections and cerebral palsy children present certain specificities which require improvements in this analgesic protocol.

Four Caucasian patients with mutations in the fukutin gene and variable clinical phenotype.

Fukuyama congenital muscular dystrophy (FCMD) is frequent in Japan, due to a founder mutation of the fukutin gene (FKTN). Outside Japan, FKTN mutations have only been reported in a few patients with a wide spectrum of phenotypes from Walker-Warburg syndrome to limb-girdle muscular dystrophy (LGMD2M). We studied four new Caucasian patients from three unrelated families. All showed raised serum CK initially isolated in one case and muscular dystrophy. Immunohistochemical studies and haplotype analysis led us to search for mutations in FKTN. Two patients (two sisters) presented with congenital muscular dystrophy, mental retardation, and posterior fossa malformation including cysts, and brain atrophy at Brain MRI. The other two patients had normal intelligence and brain MRI. Sequencing of the FKTN gene identified three previously described mutations and two novel missense mutations. Outside Japan, fukutinopathies are associated with a large spectrum of phenotypes from isolated hyperCKaemia to severe CMD, showing a clear overlap with that of FKRP.

Mitochondrial respiratory chain deficiency revealed by hypothermia.

We observed a 17-month-old girl with profound and initially isolated episodes of hypothermia. Thereafter, she developed growth delay, repetitive corneal and bone lesions. Persistent hyperlactataemia in plasma and in CSF prompted us to investigate respiratory chain enzymes. A deficit in respiratory chain complexes III and IV was demonstrated in isolated skeletal muscle mitochondria, circulating lymphocytes and fibroblasts by spectrophotometric and polarographic studies. Moreover, UCP3 mRNA expression in muscle was decreased.

Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex I deficiency.

Reduced nicotinamide adenine dinucleotide (NADH):ubiquinone oxidoreductase (complex I) is the largest complex of the mitochondrial respiratory chain and complex I deficiency accounts for approximately 30% cases of respiratory-chain deficiency in humans. Only seven mitochondrial DNA genes, but >35 nuclear genes encode complex I subunits. In an attempt to elucidate the molecular bases of complex I deficiency, we studied the six most-conserved complex I nuclear genes (NDUFV1, NDUFS8, NDUFS7, NDUFS1, NDUFA8, and NDUFB6) in a series of 36 patients with isolated complex I deficiency by denaturing high-performance liquid chromatography and by direct sequencing of the corresponding cDNA from cultured skin fibroblasts. In 3/36 patients, we identified, for the first time, five point mutations (del222, D252G, M707V, R241W, and R557X) and one large-scale deletion in the NDUFS1 gene. In addition, we found six novel NDUFV1 mutations (Y204C, C206G, E214K, IVS 8+41, A432P, and del nt 989-990) in three other patients. The six unrelated patients presented with hypotonia, ataxia, psychomotor retardation, or Leigh syndrome. These results suggest that screening for complex I nuclear gene mutations is of particular interest in patients with complex I deficiency, even when normal respiratory-chain-enzyme activities in cultured fibroblasts are observed.

Cerebral white matter disease in children may be caused by mitochondrial respiratory chain deficiency.

Several mitochondrial diseases are known to occasionally involve the cerebral white matter, namely Leigh syndrome, Kearns-Sayre syndrome, and MELAS syndrome, but in these cases the major finding is alteration in the basal ganglia and brainstem. Here we report on severe diffuse white matter involvement and respiratory chain enzyme deficiency or mitochondrial DNA rearrangement in 5 unrelated families. It is interesting that white matter lesions were the only abnormal neuroradiologic feature in 3 of the 5 families, and multiple small cyst-like white matter lesions were found in 2 of 5 probands. Respiratory chain deficiency should be considered in the diagnosis of severe white matter involvement in childhood.

Establishment of human microglial cell lines after transfection of primary cultures of embryonic microglial cells with the SV40 large T antigen.

Four continuous cell lines of human microglial cells were obtained by transfection of enriched cultures of human embryonic brain-derived macrophages with a plasmid encoding for the large T antigen of SV40. The transformed cells had the macrophagic characteristics of adherence and intra-cytoplasmic non-specific esterase activity. They could phagocytize zymosan particles but the phagocytic activity remained low. They expressed several macrophagic antigens but not the monocytic markers CD14, CD4, CD68/Ki-M6 and CD11c. The cells could be activated to express class II major histocompatibility complex antigens after interferon-gamma activation. Finally, interleukin-6 was produced spontaneously by the cells and this production was further increased after interleukin-1 alpha stimulation.

Adhesion to human neurons and astrocytes of monocytes: the role of interaction of CR3 and ICAM-1 and modulation by cytokines.

Monocytes but not unstimulated lymphocytes adhered to human neurons and astrocytes in primary culture, as demonstrated by double labeling. The expression of VCAM-1 was higher on neurons than on astrocytes, whereas that of beta 1, alpha 1, alpha 2, alpha 4 and alpha 5 chains from the integrins and of ICAM-1 was identical on both types of cells. The expression on neurons of ICAM-1, but not of integrins, was up-regulated by exogenous tumor necrosis factor (TNF) alpha, interleukin (IL)-1 alpha and interferon (IFN)-gamma. The same was observed on astrocytes associated with a sharp increase in the expression of VCAM-1. Adhesion between monocytes and neurons or astrocytes was 80% inhibited by mAbs directed against the CR3 determinant on monocytes or against ICAM-1 on neural cells but not by any of the other mAbs against adhesion proteins that were tested. Finally, the level of endogenous production of IL-1 alpha and TNF alpha was greatly increased after the adhesion of monocytes to CNS cells.

Infantile neuropathy with unstable myelin: study of the P0 protein.

An unusual form of hereditary motor and sensory neuropathy characterized by a prominent disruption of the myelin lamellae is reported. In addition to detailed morphological analysis, we investigated the protein P0, which is the major protein of peripheral myelin involved in adhesion. No major gene rearrangement and no differences in P0 protein expression were observed in the present case.

Adhesion proteins on human microglial cells and modulation of their expression by IL1 alpha and TNF alpha.

Expression of adhesion proteins on human microglial cells was studied by immunocytochemistry. Both microglial cells and peripheral blood monocytes expressed beta 2 integrins and molecules of the immunoglobulin superfamily at similar levels whereas the expression of the beta 1 integrins (alpha 2-VLA (very late antigen), alpha 4-VLA, alpha 5-VLA, alpha 6-VLA) was higher on microglial cells than on monocytes. Stimulation of microglial cells with interleukin-1 alpha and tumour necrosis factor-alpha, the main cytokines detected in HIV1-infected central nervous system (CNS), increased the microglial expression of alpha 1-VLA, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and beta 2-LFA-1 (leukocyte-function-associated molecule-1) but not of alpha L-LFA-1. Such an induction of adhesion molecules could facilitate penetration of HIV1-infected monocytes into brain parenchyma and their adhesion to CNS cells, and could maintain a chronic inflammation during human immunodeficiency virus-1 (HIV1) encephalopathy.

Human immunodeficiency virus type 1-infected monocytic cells can destroy human neural cells after cell-to-cell adhesion.

Primary cultures of human embryonic neurons and astrocytes have been used to test the interactions between neural cells and either human immunodeficiency virus type 1 (HIV-1) or HIV-1-infected monocytes. After direct infection with HIV-1, neither morphological alteration of neurons and astrocytes nor signs of viral replication were observed. Similarly, cultured human neurons and astrocytes were resistant to incubation with the supernatant of HIV-1-infected U937 cells, a human monoblastoid cell line. In contrast, HIV-1-infected U937 monocytic cells adhered to neural cells and induced large plaques of necrosis surrounding them. This cytopathic effect began at the time of viral replication (day 16 after infection). Its intensity depended on that of viral replication, and its range was identical to the region of diffusion of viral antigens, as judged by immunocytochemistry. The cytopathic effect was not dependent on the release of free radicals. It could not be induced by cytokines or cytokine-stimulated U937 cells. It is likely that this cytopathic effect depends on the release of viral antigens either within the site of adherence itself or within close range of the astrocyte membrane.