Neural correlates of consciousness and related disorders: From phenotypic descriptors of behavioral and relative consciousness to cortico-subcortical circuitry.

We report a review of medical aspects of the consciousness. The behavioral dimension, phenotypic descriptors, relative consciousness and neural correlates of consciousness and related disorders were addressed successively in a holistic and chronological approach. Consciousness is relative, specific to each individual across time and space. Historically defined as the perception of the self and the environment, it cannot be separated from behaviors, entailing an idea of conscious behavior with metapractic and metagnostic aspects. Observation of spontaneous and evoked overt behavior distinguishes three main types of disorder of consciousness (DoC): coma, vegetative state or unresponsive wakefulness, and minimally conscious or relationally impoverished state. Modern functional exploration techniques, such as imaging, increase the understanding of DoCs and consciousness. Whether consciousness is a superior function and/or an instrumental function is discussed. Neural correlates can be subdivided into two wakefulness pathways (superior thalamic cholinergic and inferior extra-thalamic), and cortico-subcortical circuitry. The deep brain structures are those described in the well-known sensorimotor, associative and limbic loops, as illustrated in the mesolimbic model of DoC. The cortices can be segregated into several overlapping networks: (1) a global workspace including thalamo-cortical loops; (2) the default mode network (DMN) and related intrinsic connectivity networks (i.e., central executive, medial DMN and salience networks); (3) a 3-fold network comprising the fronto-parietal control system and its dorsal and ventral attentional sub-networks, the fronto-parietal executive control network, and the cingulo-opercular salience network; (4) the internal and external cortices, respectively medial, turned toward the self, and lateral, turned toward the environment. The network dynamics is the reflection of consciousness, notably anticorrelations such as the decrease in activity of the posterior cingulate-precuneus regions during attentional tasks. Thanks to recent advances in DoC pathophysiology, further significative therapeutic progress is expected, taking into account the societal context. This depends notably on the dissemination of medical knowledge and its transfer to a wider public.

Lumbar puncture in infants with urinary tract infection: Assessment of infant management in the emergency department.

BACKGROUND: Neonatal bacterial infections must be bacteriologically confirmed from laboratory samples to best adjust antibiotic therapy. Lumbar puncture (LP) has been recommended for infants younger than 1 month with suspected serious bacterial infection (SBI) to manage possible meningitis. However, the incidence of bacterial meningitis associated with other infections and particularly with urinary tract infections (UTIs) is low. Recourse to systematic LP may be less essential if infants have a UTI. We aimed (a) to determine the management and frequency of bacterial meningitis coexisting with a documented diagnosis of UTI in infants aged < 1 month who had an LP, and (b) to evaluate the management of infants in emergency admissions with suspected SBI while assessing antibiotic treatment. METHODS: We conducted a retrospective single-center study from January 2010 to April 2019 including all cases of neonatal bacterial infections, and collected data on the clinical, laboratory, and radiological features. RESULTS: In all, 409 infants were included in the study. Of these, 162 (39.6%) presented with a UTI and eight (2%) had bacterial meningitis. Of the infants diagnosed with UTI, 74.7% had an LP, of whom 34.7% experienced LP complications. No coexistence of UTI and bacterial meningitis was found among infants who had an LP and a documented UTI. CONCLUSION: Although not all infants had an LP and a urine culture at the same time, these results show that bacterial meningitis coexisting with a confirmed UTI diagnosis in infants is rare. Furthermore, LP can be traumatic in some cases and therefore its utility should be assessed according to the clinical context.

Pathogenesis and therapeutic targets in spinal muscular atrophy (SMA).

Autosomal-recessive spinal muscular atrophy (SMA) is characterized by the loss of specific motor neurons of the spinal cord and skeletal muscle atrophy. SMA is caused by mutations or deletions of the survival motor neuron 1 (SMN1) gene, and disease severity correlates with the expression levels of the nearly identical copy gene, SMN2. Both genes ubiquitously express SMN protein, but SMN2 generates only low levels of protein that do not fully compensate for the loss-of-function of SMN1. SMN protein forms a multiprotein complex essential for the cellular assembly of ribonucleoprotein particles involved in diverse aspects of RNA metabolism. Other studies using animal models revealed a spatio-temporal requirement of SMN that is high during the development of the neuromuscular system and later, in the general maintenance of cellular and tissues homeostasis. These observations define a period for maximum therapeutic efficiency of SMN restoration, and suggest that cells outside the central nervous system may also participate in the pathogenesis of SMA. Finally, recent innovative therapies have been shown to mitigate SMN deficiency and have been approved to treat SMA patients. We briefly review major findings from the past twenty-five years of SMA research. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

Leukodystrophies and genetic leukoencephalopathies in children.

Leukodystrophies and genetic leukoencephalopathies are a large group of genetic disorders affecting central nervous system white matter. They can begin at any age, however this study focuses on disorders beginning in childhood and adolescence. We discuss the recent definitions, classifications, and classic syndromes, as well as genetic progress in the field through the identification of new genes and several new genetic syndromes.

[Transverse reductional anomaly and atypical fibrodysplasia ossificans progressiva: A case diagnosed late]. / Anomalie réductionnelle transverse et fibrodysplasie ossifiante progressive atypique, à propos d'un cas de diagnostic tardif.

Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by the association of congenital bone abnormalities and extraskeletal ossification flare-ups occurring in muscles and fasciae. Early diagnosis is important to prevent ossification flare-ups, but some atypical presentations can lead to errors in diagnosis and therefore delay. Here, we report on a case of an atypical presentation of FOP in a girl, in whom prominent transverse reductional abnormalities delayed diagnosis. The patient developed extraskeletal ossifications and progressive fibrosis that led to motor restrictions. Since early diagnosis is important, we discuss the clinical presentations of FOP and the differential diagnoses.

[Pedagogic focus-group in pediatrics]. / Initiation à la pédagogie narrative en pédiatrie : le focus-groupe pédagogique.

AIM: To assess a new behavioral teaching technique called "focus group pedagogy" (FGP), which consists in a three-step meeting between sick children's parents and medical students (first with students alone, then with parents and students together, then with students alone). METHODS: This qualitative research ran two sessions (each totaling four to six parents and six students) in which parents were questioned on four main themes: their knowledge of the medical hierarchy, their ability to identify the people in the hospital, their communication with medical staff, and the overall care delivered to their children. A thematic analysis of the verbatim transcript was performed. RESULTS: In the FGP sessions, medical students voiced opinions on their degree of insertion in the medical and paramedical staff, and reported their presence as ambiguous, between care and learning. Parents voiced their experience of their child's hospital stay but also their wider conception of the parent/patient-physician relationship based on their parent-of-patient/parent-as-patient experiences. The meeting of parents and students highlighted divergent narratives on relationships with caregivers, communication, attitudes, knowledge, and competencies. This approach made it possible to hear and learn the point of view "from the other side," which proved beneficial for students, session leaders, and the care unit organization alike. CONCLUSION: FGP is a novel and easy way to discover diverse narratives and the technique is feasible and beneficial in pediatric settings.

[Neurological symptoms due to Mycoplasma pneumoniae infection in nine children]. / Formes neurologiques des infections à Mycoplasma pneumoniae : à propos de neuf cas pédiatriques.

Mycoplasma pneumoniae infection is common in children. Extrapulmonary symptoms usually reveal as neurological symptoms, mainly as encephalitis with significant morbidity and mortality. Various other neurological presentations have also been reported. We describe a cohort of nine children with neurological manifestations due to M. pneumoniae infection, including five cases of encephalitis, one of polyradiculoneuritis, one of ophthalmoplegia, one of optic neuritis, and one of myositis. Progression was variable from ad integrum recovery to severe brain damage. Diagnosis is usually confirmed by PCR and/or serological follow-up, but the latter is still insufficiently used in practice to systematically affirm the diagnosis. Therapeutic management is not clearly defined and long-term progression can be uncertain despite early antibiotic and/or anti-inflammatory treatments.

Electrical modulation of neuronal networks in brain-injured patients with disorders of consciousness: a systematic review.

Six clinical studies of chronic electrical modulation of deep brain circuits published between 1968 and 2010 have reported effects in 55 vegetative or minimally conscious patients. The rationale stimulation was to activate the cortex through the reticular-thalamic complex, comprising the tegmental ascending reticular activating system and its thalamic targets. The most frequent intended target was the central intralaminar zone and adjacent nuclei. Hassler et al. also proposed to modulate the pallidum as part of the arousal and wakefulness system. Stimulation frequency varied from 8Hz to 250Hz. Most patients improved, although in a limited way. Schiff et al. found correlations between central thalamus stimulation and arousal and conscious behaviours. Other treatments that have offered some clinical benefit include drugs, repetitive magnetic transcranial stimulation, median nerve stimulation, stimulation of dorsal column of the upper cervical spinal cord, and stimulation of the fronto-parietal cortex. No one treatment has emerged as a gold standard for practice, which is why clinical trials are still on-going. Further clinical studies are needed to decipher the altered dynamics of neuronal network circuits in patients suffering from severe disorders of consciousness as a step towards novel therapeutic strategies.

[Macrocephaly-capillary malformation. A neonatal case]. / Le syndrome macrocéphalie - malformation capillaire. Intérêt du diagnostic en période néonatale.

UNLABELLED: Macrocephaly-cutis marmorata telangiectatica congenita is a multiple congenital anomaly syndrome first described in 1997 in children with macrocephaly, cutis marmorata telangiectatica congenita, and several other abnormalities. Since 2007, this syndrome has been renamed macrocephaly-capillary malformation. CASE REPORT: The pregnancy was marked by polyhydramnios associated with fetal macrosomia and macrocephaly. Clinical examination of the newborn confirmed overgrowth, macrocephaly, and found skin abnormalities with diffuse marbled skin, filtrum and upper lip vascular anomaly, and several superficial capillary malformations on the chest and abdomen, partial bilateral syndactyly between the 2nd and 3rd toes, and right hemi-hypertrophy of the body. Brain magnetic resonance imaging showed moderate right hemimegalencephaly. Radiological examination of the skeleton showed asymmetry of the limbs. At 8 months, the medical follow-up confirmed the diagnosis and its neurosurgical treatment of hydrocephalus secondary to an Arnold Chiari malformation. DISCUSSION: The patient reported herein presented macrocephaly-capillary malformation syndrome characterized by macrocephaly and more than two of the main reported findings comprising cutis marmorata, superficial vascular anomaly, syndactyly, and body asymmetry. We describe the major components of this multiple malformative syndrome that is rarely reported in the pediatric literature, especially in newborns. This syndrome should be detected early because medical multidisciplinary follow-up is necessary to prevent different complications (neurological, orthopedic, or oncologic).

[Neurological symptoms with Bartonella henselae infection: report on 2 pediatric cases]. / Atteintes neurologiques àBartonella henselae : à propos de 2 cas pédiatriques.

Cat scratch disease (CSD) is usually a benign, self-limited regional lymphadenopathy, caused by Bartonella henselae. However, systemic complications have been described. We report on 2 children who developed neurological symptoms of acute encephalitis or neuroretinitis. Cat scratch disease should be suspected when neurological symptoms of undetermined cause occur in children, whether or not anamnesis is significant.

Pediatric neurological complications associated with the A(H1N1)pdm09 influenza infection.

BACKGROUND: Influenza-related neurological complications (INC) have been reported during seasonal flu in children. OBJECTIVES: To investigate the types, outcomes and incidence of INC occurring during the 2009 A(H1N1) pandemic, a retrospective analyze was conducted in the single French pediatric hospital of Lyon from October 2009 to February 2010. STUDY DESIGN: All children presenting with fever, influenza-like illness, respiratory distress or neurological symptoms were tested for influenza A(H1N1)pdm09 infection from respiratory specimens using real time RT-PCR. RESULTS: INC occurred in 14 A(H1N1)pdm09 positive children (7.7% of A(H1N1)pdm09 positive children admitted to hospital) with a median age of 5.1 years. Admission to the intensive care unit (ICU) was required for nine children (64.3%). Half of the children with INC had comorbidity and three had coinfection, both characteristics mainly found in children requiring the ICU. All children received oral oseltamivir treatment. Febrile seizures were observed in eight children, half of them having a chronic comorbidity (2 epilepsy, 1 nonketotic hyperglycinemia, 1 anoxic encephalopathy). Other INC, less commonly reported, included 2 cases of encephalitis, 1 encephalopathy, 1 basilar artery thrombosis, 1 myasthenic crisis and 1 coma. Eleven of the 14 children (78.6%) recovered, one had a minor disability, one child developed a locked-in syndrome and one died from complications of an acute necrotizing encephalopathy. DISCUSSION: INC can be observed even in children with no underlying disorder. It may lead to dramatic issue in a significant number of cases.

Novel neuronal proteolipid protein isoforms encoded by the human myelin proteolipid protein 1 gene.

The human myelin proteolipid protein 1 gene (hPLP1), which encodes the major structural myelin proteins of the central nervous system (CNS), is classically described as expressed in the oligodendrocytes, the CNS myelinating cells. We identified two new exons in the intron 1 of the hPLP1 gene that lead to the expression of additional mRNA and protein isoforms mainly expressed in neurons instead of oligodendrocytes. Those novel neuronal PLP isoforms are detected as soon as human fetal development and their concomitant expression is specific of the human species. As classical PLP proteins, the novel protein isoforms seem to be addressed to the plasma membrane. These results suggest for the first time that PLP may have functions in humans not only in oligodendrocytes but also in neurons and could be implicated in axono-glial communication. Moreover, this neuronal expression of the hPLP1 gene might explain the neuronal dysfunctions in patients carrying hPLP1 gene mutations.

[Erythema nodosum and adenopathy in a 15-year-old boy: uncommon signs of cat scratch disease]. / Erythème noueux et adénopathies chez un adolescent: mode de révélation rare de la maladie des griffes du chat.

UNLABELLED: Erythema nodosum rarely occurs in childhood and can be caused by cat scratch disease, as a result of agent Bartonella henselae. We report the case of a teenager who presented erythema nodosum and bilateral inguinal adenitis. Cat scratch disease diagnosis was confirmed by anti-Bartonella henselae serologies. Despite an appropriate antibiotic therapy, evolution was unfavourable with adenitis abcédation requiring surgical drainage. CONCLUSION: Erythema nodosum in children must let think to cat scratch disease among others etiologies.