Rare metabolic disease mimicking COL4A1/COL4A2 fetal brain phenotype.

Pathogenic variants of collagen type IV alpha 1 and 2 (COL4A1/COL4A2) genes cause various phenotypic anomalies, including intracerebral hemorrhage and a wide spectrum of developmental anomalies. Only 20% of fetuses referred for COL4A1/COL4A2 molecular screening (fetuses with a suspected intracerebral hemorrhage) carry a pathogenic variant in these genes, raising questions regarding the causative anomaly in the remaining 80% of these fetuses. We examined, following termination of pregnancy or in-utero fetal death, a series of 113 unrelated fetuses referred for COL4A1/COL4A2 molecular screening, in which targeted sequencing was negative. Using exome sequencing data and a gene-based collapsing test, we searched for enrichment of rare qualifying variants in our fetal cohort in comparison to the Genome Aggregation Database (gnomAD) control cohort (n = 71 702). Qualifying variants in pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) were overrepresented in our cohort, reaching genome-wide significance (P = 2.11 × 10-7 ). Heterozygous PDHA1 loss-of-function variants were identified in three female fetuses. Among these three cases, we observed microcephaly, ventriculomegaly, germinolytic pseudocysts, agenesis/dysgenesis of the corpus callosum and white-matter anomalies that initially suggested cerebral hypoxic-ischemic and hemorrhagic lesions. However, a careful a-posteriori reanalysis of imaging and postmortem data showed that the observed lesions were also consistent with those observed in fetuses carrying PDHA1 pathogenic variants, strongly suggesting that these two phenotypes may overlap. Exome sequencing should therefore be performed in fetuses referred for COL4A1/COL4A2 molecular screening which are screen-negative, with particular attention paid to the PDHA1 gene. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Prognostic value of contrast-enhanced MRI in Guillain-Barré syndrome in children.

BACKGROUND: The aim of this retrospective study is to explore the prognostic value of different contrast enhancement imaging patterns in childhood Guillain-Barré syndrome by comparing the clinical, laboratory, and therapeutic outcomes. METHODS: We included a total of 37 patients who were diagnosed and followed up by a pediatric neurology team at Montpellier University Hospital between 2000 and 2016. All images were reinterpreted by the first author and a senior pediatric neuroradiology staff member in two different sessions; in the case of disagreement, the expert's reading was considered. RESULTS: The study group comprised 22 (59.5%) boys and 15 (40.5%) girls. The age ranged from 1.5 year to 14.8 years. Muscle weakness was present in 33 (89.2%) patients. Cranial nerves involvement was observed in 22 (59.5%) patients, while 29 (78.4%) patients had albuminocytological dissociation. In 27 (73%) patients, contrast enhancement or thickening of the lumbosacral nerve roots was found. Simultaneous spinal nerve root and cranial nerve enhancement was noted in five (17.2%) patients, while isolated cranial nerve enhancement was identified in three (10.3%) patients. Clinical and radiological cranial nerve involvement was found in seven (18.9%) patients, while isolated clinical cranial nerves involvement occurred in 13 (35.1%) patients. No significant correlation between different magnetic resonance imaging (MRI) enhancement patterns and short-term or long-term outcomes was found in our cohort. CONCLUSION: Contrast-enhanced brain and spinal MRI is a sensitive and recommended supportive test for diagnosing acute inflammatory polyradiculopathy in children. Its predictive value for clinical, and therapeutic outcomes in the short or long term has not yet been proved.

Pediatric deep neck infections: Clinical description and analysis of therapeutic management.

OBJECTIVES: The aim of our study was to describe clinical presentations, bacteriological results, and therapeutic management in a pediatric population presenting with acute pharyngeal suppuration. A further aim was to identify clinical, bacteriological, and radiological predictors of success associated with exclusive medical treatment. METHOD: A retrospective study was carried out including patients under 18 years of age hospitalized between January 1, 2015 and December 31, 2017 in our center for acute pharyngeal suppuration. We identified three groups of patients: group A, treated with exclusive intravenous antibiotics; group B, surgically treated after 48 h of appropriate antibiotic therapy, due to persistent fever and/or clinical worsening and/or persistence of a collection on follow-up imaging; group C, surgically treated as first-line therapy in association with intravenous antibiotics. A total of 83 patients were included: 36 in group A, 12 in group B, and 35 in group C. These three groups were compared for several variables: age of the patients, polynuclear neutrophil counts, diameter of the collections (the largest diameter found on imaging), duration of antibiotic therapy, delay before return to apyrexia, and hospitalization duration. RESULTS: A neck mass and torticollis were present, respectively, in 48.8 and 47.6% of cases. No breathing difficulties were reported. Streptococcus pyogenes was the most frequently identified microorganism. The average diameter of the collections from patients treated surgically as first-line therapy (group C) was significantly larger than that of the patients treated with antibiotics (group A) (27.89 mm vs. 18.73 mm, respectively, p = 0.0006). All the patients who required surgery despite 48 h of appropriate antibiotic therapy (group B) had collections with diameters greater than or equal to 15 mm. There was no significant difference between the groups concerning hospitalization duration. CONCLUSION: Exclusive medical treatment is associated with a high cure rate, mainly for collections with small diameter. We recommend special attention to patients treated with first-line exclusive intravenous antibiotic therapy and with a collection diameter greater than or equal to 15 mm.

[Acute methotrexate-related neurotoxicity and pseudo-stroke syndrome]. / Neurotoxicité aiguë secondaire au méthotrexate et « pseudo-stroke ¼ syndrome.

Treatment of acute lymphoblastic leukemia requires high-dose systemic and/or intrathecal methotrexate to prevent and/or treat central nervous system disorders. Acute neurotoxicity of methotrexate, of unknown etiopathogenesis, is characterized by the polymorphism of clinical manifestations, responsible for a potentially harmful diagnostic delay in these immunosuppressed patients. We describe five episodes of transient acute leukoencephalopathy mimicking a stroke, reported in the literature as "pseudo-stroke syndrome". Neurologic symptoms occurred 3-10 days after IV or IT methotrexate and manifested as aphasia and alternating sensorimotor deficit. The fluctuating symptomatology regressed completely within a few days. Brain MRI, which is essential for diagnosis, demonstrated early white matter diffusion restriction in the affected cerebral area. These anomalies disappeared in one week, while hyperintense T2 FLAIR signals developed in the corresponding brain areas. The long-term progression of these pseudo-stroke patients was favorable, without any therapeutic modification. Nevertheless, the involvement of transient acute leukoencephalopathy episodes in the progressive onset of neuro-cognitive disorders is discussed.

[Bilateral facial nerve palsy associated with Epstein-Barr virus infection in a 3-year-old boy]. / Paralysie faciale bilatérale au cours d'une infection à virus d'Epstein­Barr.

Bilateral facial nerve palsy is a rare and sometimes difficult diagnosis. We describe a case of bilateral simultaneous facial nerve palsy associated with Epstein-Barr virus (EBV) infection in a 3-year-old boy. Several symptoms led to the diagnosis of EBV infection: the clinical situation (fever, stomachache, and throat infection), white blood cell count (5300/mm3 with 70% lymphocyte count), seroconversion with EBV-specific antibodies, lymphocytic meningitis, and a positive blood EBV polymerase chain reaction (9.3×103 copies of EBV-DNA). An MRI brain scan showed bilateral gadolinium enhancement of the facial nerve. A treatment plan with IV antibiotics (ceftriaxone) and corticosteroids was implemented. Antibiotics were stopped after the diagnosis of Lyme disease was ruled out. The patient's facial weakness improved within a few weeks. Bilateral facial nerve palsy is rare and, unlike unilateral facial palsy, it is idiopathic in only 20% of cases. Therefore, it requires further investigation and examination to search for the underlying etiology. Lyme disease is the first infectious disease that should be considered in children, especially in endemic areas. An antibiotic treatment effective against Borrelia burgdorferi should be set up until the diagnosis is negated or confirmed. Further examination should include a blood test (such as immunologic testing, and serologic testing for viruses and bacterium with neurological tropism), a cerebrospinal fluid test, and an MRI brain scan to exclude any serious or curable underlying etiology. Facial bilateral nerve palsy associated with EBV is rarely described in children. Neurological complications have been reported in 7% of all EBV infections. The facial nerve is the most frequently affected of all cranial nerves. Facial palsy described in EBV infections is bilateral in 35% of all cases. The physiopathology is currently unknown. Prognosis is good most of the time.

Complications and follow up of subarachnoid hemorrhages.

Complications of subarachnoid hemorrhage are the major life threatening and functional components of the follow up of a ruptured aneurysm. Knowing how to identify these is a key challenge. They vary in type throughout the postoperative follow up period. The aim of this article is firstly to list the main complications of the acute phase (rebleeding, acute hydrocephalus, acute ischemic injury and non-neurological complications), the subacute phase (vasospasm) and the chronic phase of subarachnoid hemorrhages: (chronic hydrocephalus and cognitive disorders) and to describe their major clinical and radiological features. Secondly, we describe the long-term follow up strategy for patients who have suffered a subarachnoid hemorrhage and have been treated endovascularly or by surgery. This follow up involves a combination of clinical consultations, cerebral MRI and at least one review angiogram.

[Mitochondrial neurogastrointestinal encephalopathy disease]. / L'encéphalomyopathie neuro-gastro-intestinale mitochondriale : un tableau d'anorexie mentale atypique.

Mitochondrial neurogastrointestinal encephalopathy disease (MNGIE) is a rare autosomal-recessive syndrome, resulting from mutations in the TYMP gene, located at 22q13. The mutation induces a thymidine phosphorylase (TP) deficit, which leads to a nucleotide pool imbalance and to instability of the mitochondrial DNA. The clinical picture regroups gastrointestinal dysmotility, cachexia, ptosis, ophthalmoplegia, peripheral neuropathy, and asymptomatic leukoencephalopathy. The prognosis is unfavorable. We present the case of a 14-year-old Caucasian female whose symptoms started in early childhood. The diagnosis was suspected after magnetic resonance imaging (MRI), performed given the atypical features of mental anorexia, which revealed white matter abnormalities. She presented chronic vomiting, postprandial abdominal pain, and problems gaining weight accompanied by cachexia. This diagnosis led to establishing proper care, in particular an enteral and parenteral nutrition program. There is no known specific effective treatment, but numerous studies are in progress. In this article, after reviewing the existing studies, we discuss the main diagnostic and therapeutic aspects of the disease. We argue for the necessity of performing a cerebral MRI given the atypical features of a patient with suspected mental anorexia (or when the clinical pattern of a patient with mental anorexia seems atypical), so that MNGIE can be ruled out.

Partial acute transverse myelitis is a predictor of multiple sclerosis in children.

BACKGROUND: Acute transverse myelitis (ATM) in children is a rare and often severe disease for which there are few known prognostic factors, particularly the subsequent risk of multiple sclerosis (MS) diagnosis. OBJECTIVES: To determine the clinical course and prognostic factors after a first episode of ATM in children. METHODS: Thirty children below 16 years of age diagnosed with a first neurological episode of ATM were included retrospectively. Clinical evaluation, treatment, laboratory, and MRI data were collected. RESULTS: Median age at onset was 11 years (range 3-15 years). Follow-up data were available for a median of 4 years (range 0.5-16.7 years). Five patients subsequently had a diagnosis of MS (17%), which was associated with acute partial transverse myelitis (odds ratio 5; 95% confidence interval 2.3-11), with a 60% probability of having a relapse at five years (p < 0.01). The 2011 Verhey criteria correctly identified MS in children with the highest specificity (96%) and sensitivity (80%). CONCLUSION: Acute partial transverse myelitis and brain MRI abnormalities at initial presentation are significantly predictive of a subsequent diagnosis of MS in children with ATM. These findings suggest that closer brain MRI monitoring after acute partial transverse myelitis might make the earlier introduction of disease-modifying therapies possible.

The olfactory system.

Any dysfunction in olfaction requires a radiological exploration comprising the nasal cavity, the anterior base of the skull, in particular the frontal and temporal lobes. MRI is the reference examination, due to the frontal plane and the T1, T2 volume maps. In the child, aplasia of the olfactory bulbs falls within a polymalformation (CHARGE) or endocrine (Kallman) context. In the adult, rhino sinus disease and meningiomas are the most common etiologies. Frontal or temporal impairment: tumoral or vascular and neurodegenerative disorders (Parkinson's disease) may accompany a loss of olfaction.

Imaging of the optic chiasm and retrochiasmal visual pathways.

The exploration of the chiasmal and retrochiasmal visual pathways is based on magnetic resonance imaging. A bitemporal hemianopsis suggests a lesion of the optic chiasm while homonymous lateral hemianopsis should lead to a search for a lesion of the retrochiasmal visual pathways. The causes of chiasmal impairment are mainly tumoral. The exploration protocol is based on MRI with T1-weighted sagittal sections, then T2- and T1-weighted coronal sections with and without injection. In case of a retrochiasmal syndrome, the MRI exploration protocol is a function of the type of occurrence of the deficiency and the context.

Imaging of the pre-chiasmatic optic nerve.

Damage to the optic nerve (ON) is characterised by a reduction in visual acuity. Pre-chiasmatic lesions to the optic nerve may be of traumatic, congenital, tumoral (meningioma, glioma), inflammatory or vascular origins. In all cases, MRI is the choice means of exploration, carried out with axial and coronal sections with a thickness of 2.5-3mm and T1 and T2-weighted spin echo sequences. The coronal sections may be carried out with fat signal saturation for an elective study of the size of the retrobulbar portion of the ON.

[Mandibular asymmetry in plagiocephaly without synostosis]. / Etude de l'asymétrie mandibulaire dans les plagiocéphalies sans synostose.

SUBJECT: The number of plagiocephalies without synostosis (PWS) strongly increased in the last decade. Its impact on the mandible remains badly understood, the more so as there are various forms of PSS. The purpose of this study was to analyze mandible deformation according to the deformation of PWS. MATERIAL AND METHODS: The study was carried out retrospectively starting from three-dimensional scans of children presenting with a PWS. They were classified in 2 groups according to the deformation of the cranium. There were 51 frontal plagiocephalies (PF) and 19 occipital plagiocephalies (PO) for which the cephalic index was calculated. The position of the mandible compared to the base of cranium and its intrinsic asymmetry were analyzed (paired parametric Student test). RESULTS: The mandible was symmetrical in PO whereas it was asymmetrical for PF. This asymmetry was present at the level of the corpus and developed in 2 ways: that is to say asymmetry compensated for that of the base of the cranium (68.6%); or it worsened it (23.5%). The degree of brachycephaly was more important in PO than the PF with a cranial index of 0.93+/-0.07 and 0.85+/-0.07 respectively (P<0.05). In both cases the position of the mandibular condyle followed the asymmetry of the base of cranium and the asymmetry of the temporomandibular joint (TMJ) was secondary with that of the base of cranium. DISCUSSION: In addition to the asymmetry of TMJ position there was an intrinsic mandibular asymmetry in PF which was not found in PO. This asymmetry of the mandible was variable but in most cases it tended to compensate for the asymmetry of the base of the cranium which was more important in PF. The risk to have asymmetry of dental occlusion seems more important in PF than in PO, and an orthodontic follow-up appeared to be justified for these children.

[Study of the morphologic variations of the scaphocephaly. Deduction for their systematisation]. / Etude des variations morphologiques des scaphocéphalies. Implication pour leur systématisation.

PURPOSE: The scaphocephaly is the most frequent craniosynostosis secondary to a premature synostosis of the sagittal suture. Despite this univocal pathogeny there are a great heterogeneity in the skull deformation and their systematisation stay imprecise. The aim of this study was to analyse the different morphology of the scaphocephaly by 3D CT-scan to clarify the different shapes. MATERIAL AND METHODS: This retrospective study was done from the morphometric analysis of forty-two 3D CT-scan (10 girls and 32 boys). The scaphocephaly was classified in two groups according to the systematisation of Stricker and Montaut: the sphenocephaly (large forehead) and the leptocephaly (narrow forehead). The variation of the calvaria shape was analysed and different index were calculated. RESULTS: There were 30 sphenocephaly and 12 leptocephaly. Excepted for the forehead deformation there was a morphometric difference of the occipital pole that was backward rotated in the leptocephaly. In the two groups there were retro-coronal constriction (40.5%) or pre-lambdoid constriction (9.5%) independently of the sagittal synostosis degree. CONCLUSIONS: The morphometric analysis shows that the deformation of the skull secondary to the premature synostosis of the sagittal suture can be different. The adaptative defect of the metopic suture can be to explain this difference. This deformation can be harmonious, or with a retro-coronal constriction resulting in a bitemporal narrowing, or with a pre-lambdoid constriction resulting in an occipital chignon. These results conduce to qualify the surgical correction to adapt at the different shapes.

Plagiocephaly: morphometry of skull base asymmetry.

The aim of this study was to perform a morphometric analysis of the skull base to understand the mechanism of asymmetry between malformational and deformational plagiocephaly. Since 1988, we have carried out 102 CT scans with three-dimensional reconstruction of the endocranial side of the skull base. There were 20 cases of malformational plagiocephaly, consisting of 18 unicoronal synostoses (UCS) and two unilambdoid synostoses (ULS), and 82 cases of plagiocephaly without synostosis, made up of 60 cases of frontal plagiocephaly (FP) and 22 of occipital plagiocephaly (OP). The skull base asymmetry was analyzed in three ways: (1) the hemibases and the cranial fossa angles were compared with each other; (2) the structural asymmetry of the chondrocranium was calculated; and (3) the architectural asymmetry was measured in relation to the medio-labyrinthine plane. The skull base asymmetry of malformational plagiocephaly was located in the anterior and middle cranial fossae for UCS and in the posterior and middle cranial fossae for ULS. The asymmetry was the result of a localized structural anomaly of the chondrocranium. The asymmetry of deformational plagiocephaly corresponded to a distortion in relation to the medio-labyrinthine plane while the chondrocranium remained symmetric. The skull base asymmetry of malformational plagiocephaly is secondary to a localized malformation of the chondrocranium, and that of the deformational plagiocephaly is secondary to an architectural deformation.

[Clinico-radiological study of the skull deformation in the plagiocephaly without synostosis]. / Etude clinico-radiologique des déformations du crâne dans les plagiocéphalies sans synostose.

UNLABELLED: The aim of this study was to analyze the mechanism of the skull deformation observed in frontal and occipital plagiocephaly without synostosis. POPULATION AND METHODS: From 1987 to 2001, 96 plagiocephalies without synostosis, 72 males and 24 females, were examined. There were 72 Frontal Plagiocephalies (FP) and 24 Occipital Plagiocephalies (OP). The clinical examination of the neck muscles was performed to find out a torticolis with or without retraction. All patients underwent a 3D CT scan of the skull to exclude a craniostenosis. Cephalic Index (CI) was also calculated. RESULTS: The FP had a torticollis in 89.3% of cases associated with a muscle retraction (54.8%), a tonus asymmetry (16.6%), or in association (28.6%). The skull had a parallelepiped shape and the greater axis was oblique. The CI was 0.85. The OP had a torticollis in 50% of case associated with a retraction (28.6%), a tonus asymmetry (57.1%), or the association (14.3%). The skull had a square shape with an occipital flat and the CI was 0.95. DISCUSSION: The FP and OP are two deformations whose mechanism is different. The FP corresponds to a three plans skull asymmetry secondary to muscle traction on the base of the skull, and the OP corresponds to a posterior localized asymmetry of the skull secondary to compression. CONCLUSION: The traction and/or compression deformation start in utero or in the newborn period and the supine position is an aggravating positional factor.

[Acute myelitis of an unusual cause in a child: the lymphocytic choriomeningitis virus]. / Les myélites aiguës de l'enfant, à propos d'une cause rare: le virus de la chorioméningite lymphocytaire.

UNLABELLED: Acute transverse myelitis is a rare disorder in childhood. It usually occurs as a post-infectious disease, but a precise infectious agent is identified in only 20% of cases. OBSERVATION: The diagnosis of acute transverse myelitis was made in a 5.5-year-old girl who initially presented with left Claude-Bernard-Horner syndrome and meningitis. A few days later, motor and sensory tetraparesia with bladder dysfunction was observed. Magnetic resonance imaging showed a diffuse lesion in the medulla, with a hypersignal in the T2 and a hyposignal in the T1 sequences. Serum analysis showed the presence of a viral infection due to the lymphocytic choriomeningitis (LCM) virus. The outcome was marked by complete recovery of the sensorimotor deficit, but a persistence of the left Claude-Bernard-Horner syndrome. CONCLUSION: In rare cases, the LCM virus is responsible for myelitis. In the present case, the Claude-Bernard-Horner syndrome was secondary to the cervico-medullary lesion. Recent reports in the literature have been discussed, in particular as regards the use of immunomodulatory therapy, which clearly improves patient prognosis.

[Imaging of cloverleaf skull]. / Imagerie du crâne en trèfle.

The cloverleaf skull is a rare and due to complex craniosynostosis. This malformation can be isolated or associated with extracranial skeletal anomalies. This anomaly has a poor prognosis both in terms of neurological outcome and esthetic appearance. Our report underscores the need to obtain a global study of the skull, the brain and the cerebral vessels with 3D reconstructions and MRI prior to early surgery.

[Imaging of oto-mandibular dysplasias]. / Imagerie des dysplasies oto-mandibulaires.

The modern imaging opened a possibility of precise exploration of otomandibular dysplasias. The techniques of browsing by IRM and CT Scan and the software of image processing which is associated with these techniques (three-dimensional, superposition and removing of the anatomical structures) allow to carry out a true anatomical dissection of the whole of these malformative syndromes. The study of the skeletal anomalies gains by specifying the disorders of development of the various mandibular segments: temporomandibular joint, ramus and horizontal branch and also, all cranio-maxillar structures: orbital rim, cranial basis. Study of masticatory muscles shows an important damage correlated with skeletal troubles and performs a grading of morphological and functional gravity. This analytical study emphasizes some malformative axis: malar axis in cases of mandibulofacial dystosis, temporomandibular axis in hemifacial microsomia. Modern imaging can appreciate, by development of three-dimensional cephalometry, growth anomalies and quantification of post therapeutical results. At last usefulness of imaging appears in therapeutic modelisation and in the field of Computer-Aided Planning of surgical techniques of osteotomies and overall maxillaries distractions.

[Congenital skull depression. Report of 2 cases]. / Dépression congénitale de la voûte crânienne. A propos de deux cas.

Congenital depression of the fetal skull is a rare lesion (1 to 2.5 per 10,000 births) resulting in an asymmetrical skull. This depression is caused by exaggerated or prolonged pressure applied to the fetal head in utero or during delivery. Two types of congenital skull depression have been described: deformity without fracture and depression with fracture, the more common form. Congenital skull depression is important because it may be associated with underlying brain injury, especially when the depression is associated with fracture. The simple permanent cosmetic deformity may also constitute a complication. CT scan can now rule out intracranial complications and in this case, a conservative management is reasonable treatment option. The observation period should not exceed six months. After this period, orthopedic or surgical management may be indicated because spontaneous elevation of depression is uncommon after six months. The authors report two cases of congenital skull depression with deformity without fracture. The pathogenesis and treatment are discussed.

[Mycoplasma pneumoniae meningoencephalitis]. / Méningoencéphalite à Mycoplasma pneumoniae.

BACKGROUND: Severe central nervous system diseases, such as encephalitis, have been reported in association with Mycoplasma pneumoniae infections. CASE REPORT: After an ENT infection, a 9-year-old boy with Down's syndrome developed encephalitis revealed by an acute alteration in consciousness. Head computed tomography showed, after 2 weeks, an infiltration in the basal ganglia region. The diagnosis of Mycoplasma pneumoniae encephalitis was made; recovery was complete in a few weeks. CONCLUSION: Mycoplasma pneumoniae infection should be considered in all cases of acute encephalopathy; yet the pathogenesis of the disorder is unknown and the treatment uncertain.