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Biomedical subjects

F Brunelle

Publications and source records attributed to F Brunelle.

At least 19 recordsLinked to original sources

Molar tooth sign and superior vermian dysplasia: a radiological, clinical, and genetic study.

We have identified a group of 13 patients with a homogeneous radiological pattern at MRI consisting of the molar tooth sign (MTS) and superior vermian dysplasia. The patients represent a relatively heterogeneous clinical group with variable severity of developmental delay, ataxia, hypotonia, and apnea. Careful examination of MRI prompted us to split our series of patients into two groups, based on IVth ventricle dilatation. In 4/13 patients the IVth ventricle was judged to be dilated and those patients were less severely affected while most clinically affected patients had a normal IVth ventricle. DNA samples of blood leukocytes from 6/13 consanguineous patients were genotyped using polymorphic markers encompassing the Joubert syndrome loci. We therefore sequenced AHI1 located in 6q23 in two patients who were homozygous at the locus and in four sporadic cases. Only one homozygous nonsense mutation was identified. Clinically, the patient exhibiting the AHI1 mutation was the most severely affected child with a profound encephalopathy, major hypotonia, ataxia, Leber congenital amaurosis, and normal IVth ventricle at the MRI. The present study suggests that the syndrome associating MTS and dysplasia of the superior vermis of the cerebellum is a clinically and genetically heterogeneous entity and that Jouberin (AHI1) mutations account for a marginal fraction of patients.

Abnormalities, Multiple↗

Contribution of fetal MR imaging in the prenatal diagnosis of Zellweger syndrome.

Zellweger syndrome (ZS), or cerebrohepatorenal syndrome, was the first described peroxisomal biogenesis disorder. It represents the most severe phenotype, and some of its multiple congenital anomalies can manifest prenatally. Fetal hypokinesia, renal hyperechogenicity, and cerebral ventricular enlargement are the most common reported fetal features. Single and/or late detectable manifestations account for most of the difficulties of prenatal diagnosis, as well as the limitations of ultrasonography itself. Prenatal diagnosis, however, can be achieved through (1) assays of concentrations of peroxisomal metabolites (very-long-chain fatty acids, bile acids, intermediates, plasmalogens), (2) activities of peroxisomal enzymes (dihydroacetone-phosphate acyltransferase), or (3) molecular screening techniques, if available. We report on the contribution of MR imaging to the diagnosis of ZS in 2 unrelated fetuses. MR imaging was performed in the third trimester because of cerebral ventricular enlargement diagnosed on routine sonography examinations. In both cases, MR imaging revealed ZS-characteristic abnormal cortical gyral patterns, impaired myelination, and cerebral periventricular pseudocysts. In addition, MR imaging revealed renal microcysts and hepatosplenomegaly in one case. The high level of resolution of MR imaging, which allows analysis of cerebral gyration and myelination, facilitates the prenatal diagnosis of complex polymalformative syndromes such as ZS.

Abortion, Eugenic↗

[Multislice CT scan in congenital heart disease].

The management of congenital cardiovascular malformations is a diagnostic challenge. It requires accurate assessment of the intra- and extra-cardiac malformations. Three-dimensional imaging by the multislice CT scanner is now a routine investigation for congenital heart disease, complementary to echocardiography, and, increasingly, an alternative to conventional angiography. Three dimensional imaging is particularly useful in the diagnosis of complex congenital heart disease, in the preparation of complex investigations of interventional cardiac catheterisation and the postoperative evaluation of surgical repair. This report describes the different acquisition protocols adapted for children and illustrates the present role of volumic CT scanner in congenital heart disease by clinical examples of everyday clinical practice.

Child↗

Parieto-occipital grey matter abnormalities in children with Williams syndrome.

Williams syndrome (WS) is a neurodevelopmental disorder resulting from a hemizygous deletion of chromosome 7q11.23. The phenotype of WS consists of typical dysmorphic features, supravalvular aortic stenosis, infantile hypercalcemia and growth retardation. While language and facial recognition seem to be relatively spared, visuospatial constructive disabilities are a hallmark of the neurobehavioral profile of WS. In order to search for actual structural abnormalities underlying this precisely defined neurodevelopmental disorder, we performed anatomical magnetic resonance imaging (MRI) in 9 WS children (11.6 +/- 3.1 years; age range: 5.5-15 years) and 11 normal age-matched control children (11.8 +/- 2.2 years; age range: 8-15 years) using voxel-based morphometry (VBM). VBM is a fully automated whole-brain technique that delivers a voxel-wise assessment of regional grey and white matter concentration. A significant decrease in grey matter concentration was detected in the left parieto-occipital region of WS children (P < 0.05 corrected height threshold). The location of this abnormality in WS children coincides with the location of the structural abnormality previously described using the same method in 13 WS adults. These parieto-occipital abnormalities are consistent with the cognitive profile of WS which includes severe visuospatial construction and numerical cognition deficits. The demonstration of identical structural abnormalities in both adults and children argues for their early origin. Additionally, our study provides support for the use of advanced structural imaging techniques in children, in order to improve our understanding of neurobehavioral phenotypes associated with well-defined genetic disorders.

Adolescent↗

[Congenital hyperinsulinism in newborn and infant].

Congenital hyperinsulinism (HI) is the most important cause of hypoglycaemia in early infancy. The inappropriate oversecretion of insulin is responsible for profound hypoglycaemias requiring aggressive treatment to prevent severe and irreversible brain damage. Several classifications of HI can be attempted, based on: 1) the onset of hypoglycemia in the neonatal period or later in infancy; 2) the histological lesion: focal or diffuse; 3) the genetic transmission: sporadic, recessive, or less frequently dominant. The most common underlying mechanism of HI is dysfunction of the pancreatic ATP-sensitive potassium channel (K(+)(ATP)). The 2 subunits of the K(+)(ATP) channel are encoded by either the sulfonylurea receptor gene (SUR1 or ABCC8) or the inward-rectifying potassium channel gene (KIR6.2. or KCNJ11), both located in the 11p15.1 region. Focal CHI has been shown to result from a paternally inherited mutation on the SUR1 or KIR6.2 gene and loss of the maternal 11p15 allele restricted to the pancreatic lesion. Diffuse HI, frequently due to mutations of the SUR1 or KIR6.2 genes of autosomal recessive inheritance is genetically heterogeneous. The distinction between the focal and the diffuse HI is very important, because the treatments are different. To distinguish between focal and diffuse HI, transhepatic catheterisation with pancreatic venous sampling was the reference technique, but will likely be replaced by [(18)F] Fluoro-L-Dopa PET scan, which is easier to perform. In absence of response to the medical treatment (diazoxide) a limited pancreatectomy permits to cure focal HI, while a diffuse HI requires a subtotal pancreatectomy with high risk of subsequent diabetes mellitus.

ATP-Binding Cassette Transporters↗

Congenital hyperinsulinism and mosaic abnormalities of the ploidy.

BACKGROUND: Congenital hyperinsulinism and Beckwith-Wiedemann syndrome both lead to beta islet hyperplasia and neonatal hypoglycaemia. They may be related to complex genetic/epigenetic abnormalities of the imprinted 11p15 region. The possibility of common pathophysiological determinants has not been thoroughly investigated. OBJECTIVE: To report abnormalities of the ploidy in two unrelated patients with congenital hyperinsulinism. METHODS: Two patients with severe congenital hyperinsulinism, one overlapping with Beckwith-Wiedemann syndrome, had pancreatic histology, ex vivo potassium channel electrophysiological studies, and mutation detection of the encoding genes. The parental genetic contribution was explored using genome-wide polymorphism, fluorescent in situ hybridisation (FISH), and blood group typing studies. RESULTS: Histological findings diverged from those described in focal congenital hyperinsulinism or Beckwith-Wiedemann syndrome. No potassium channel dysfunction and no mutation of its encoding genes (SUR1, KIR6.2) were detected. In patient 1 with congenital hyperinsulinism and Beckwith-Wiedemann syndrome, paternal isodisomy for the whole haploid set was homogeneous in the pancreatic lesion, and mosaic in the leucocytes and skin fibroblasts (hemihypertrophic segment). Blood group typing confirmed the presence of two erythroid populations (bi-parental v paternal only contribution). Patient 2 had two pancreatic lesions, both revealing triploidy with paternal heterodisomy. Karyotype and FISH analyses done on the fibroblasts and leucocytes of both patients were unremarkable (diploidy). CONCLUSIONS: Diploid (biparental/paternal-only) mosaicism and diploid/triploid mosaicism were present in two distinct patients with congenital hyperinsulinism. These chromosomal abnormalities led to paternal disomy for the whole haploid set in pancreatic lesions (with isodisomy or heterodisomy), thereby extending the range and complexity of the mechanisms underlying congenital hyperinsulinism, associated or not with Beckwith-Wiedemann syndrome.

Chromosome Aberrations↗

Fetal hemangiopericytoma with an associated cerebral anomaly.

We report the first case of infantile hemangiopericytoma explored prenatally by fetal ultrasonography and magnetic resonance imaging (MRI). It was associated with a developmental cerebral anomaly identified on MRI. The largest lesions of the multifocal hemangiopericytoma were located in the soft tissue adjacent to the left temporal bone, and smaller lesions were found in the lumbar area and in the retroperitoneum. MRI showed no connection between the tumor and the fetal brain but there was anomalous cerebral gyration in the region and the Sylvian fissure beneath the tumor was enlarged. The pregnancy was terminated because of the severe brain anomalies and postmortem examination confirmed the prenatal findings. Microscopic analysis of the tumor tissue showed branching vessels which are typical of hemangiopericytoma. The lesions in our case occurred in association with macrosomia with visceromegaly detected at autopsy, suggesting a possible role of tumor suppressor genes.

Abnormalities, Multiple↗

Prenatal prognosis of congenital diaphragmatic hernia using magnetic resonance imaging measurement of fetal lung volume.

OBJECTIVES: To investigate the correlation between fetal lung volume (FLV), measured with magnetic resonance imaging (MRI), and postnatal mortality in newborns with prenatally diagnosed isolated congenital diaphragmatic hernia (CDH). METHODS: In a 4-year prospective multicenter study, 77 fetuses with isolated CDH diagnosed between 20 and 33 weeks' gestation underwent fast spin-echo T2-weighted lung MRI. These MRI-FLV measurements were compared with a previously published normative curve obtained in 215 fetuses without thoracoabdominal malformations and with normal ultrasound biometric findings. FLV measurements were correlated with postnatal survival. The mean gestational age at MRI was 31.3 weeks. RESULTS: The measured/expected FLV ratio was significantly lower in the newborns with CDH who died compared with those who survived (23.6 +/- 12.2 vs. 36.1 +/- 13.0, P < 0.001). When the ratio was below 25%, there was a significant decrease in postnatal survival (19% vs. 40.3%, P = 0.008). Survival was significantly lower for neonates when one lung could not be seen by fetal MRI compared with those fetuses with two visible lungs on MRI (17.9% vs. 62.1%, P < 0.001). CONCLUSION: In isolated CDH, FLV measurement by MRI is a good predictor of postnatal mortality due to pulmonary hypoplasia.

Female↗

Dominantly inherited hyperinsulinaemic hypoglycaemia.

Congenital hyperinsulinism (HI), the most important cause of hypoglycaemia in early infancy, is a heterogeneous disease with two types of histological lesions, focal and diffuse, with major consequences in terms of surgical approaches. In contrast to focal islet-cell hyperplasia, always sporadic to our knowledge, diffuse hyperinsulinism is a heterogeneous disorder involving several genes, various mechanisms of pathogenic mutations and different transmissions: (i) channelopathy involving the genes encoding the sulphonylurea receptor (SUR1) or the inward-rectifying potassium channel (Kir6.2) in recessively inherited HI or more rarely dominantly inherited HI; (ii) metabolic disorders implicating the short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) enzyme inrecessively inherited HI, the glucokinase gene (GK), the glutamate dehydrogenase gene (GLUD1) when hyperammonemia is associated, dominant exercise-induced HI with still-unknown mechanism, and more recently the human insulin receptor gene in dominantly inherited hyperinsulinism. Thus, dominant HI disorders always correspond to diffuse HI, where most hypoglycaemia occur in infancy, and are sensitive to medical treatment. Channel causes could be due to dominant negative mutation with one abnormality in channels composed of four Kir6.2 subunits and four SUR1 subunits, leading to a complete destruction of the channel structure or function, or due to haploinsufficiency with only one functional allele, leading to 50% of functional protein, which is not sufficient to obtain enough opened channels to maintain the membrane depolarized. Metabolic causes are due to a gain of function of enzyme activity (deregulated enzymes), except for physical exercise-induced hyperinsulinaemic hypoglycaemia, of still-unknown cause. Congenital hyperinsulinism (HI) is the most important cause of hypoglycaemia in early infancy (Aynsley-Green et al 2000; Cornblath et al 1990; Pagliara et al 1973; Thomas et al 1977). The inappropriate oversecretion of insulin is responsible for profound hypoglycaemia that requires aggressive treatment to prevent severe and irreversible brain damage (Volpe 1995). HI is a heterogeneous disease associated with several genes, various mechanisms of pathogenic mutations and different transmissions (Dunne et al 2004).

Exercise↗

[Congenital hyperinsulinism of infancy: surgical treatment in 60 cases of focal form].

Congenital hyperinsulinism of infancy is a severe disease that leads to important brain damage. Two different forms of the disease have been identified by pathologists: a diffuse and a focal form. A specific genetic anomaly identified in focal forms has never been described in diffuse ones. However, for most of authors, failure of medical treatment results in near-total pancreatectomy in all cases, which ends in diabetus. The aim of this retrospective study was to assess the results of elective partial pancreatectomy performed in 60 cases of focal form of hyperinsulinism over the last 18 years. Fifty-eight patients were cured with euglycemia at both fasting and hyperglycaemic tests without insulin-dependent diabetes mellitus. One patient is still in hypoglycaemia from unrecognized lesion; insulin-dependent diabetes mellitus occurred in one case nine years after surgery (a near-total pancreatectomy has been performed because of unknown focal form, in 1985).

Biopsy↗

[Imaging of pediatric head injury].

Head injury is the leading cause of death and disability during the first two decades of life. Fifty percent of deaths are due to motor vehicle accidents and falls except in infants where death is due to abuse in 80% of cases. Medical imaging during early management of patients has significantly changed the prognosis of these injuries. The main types of injuries and their appearances at different imaging modalities will be reviewed. CT remains a valuable tool but MRI also is helpful at the time of initial evaluation as well as for prognostic evaluation.

Child↗

Association of a fetal quadrigeminal cyst with a possibly congenital thalamic astrocytoma.

CASE REPORT: This article reports on the exceptional association of a fetal quadrigeminal malformative cyst with a possibly congenital pilocytic astrocytoma of the pulvinar. Both the cyst and the tumor required treatment due to their postnatal growth. DISCUSSION: Treatment modalities and difficulties are emphasized, as well as the difficulties of prenatal counseling.

Adult↗

The surgical management of congenital hyperinsulinemic hypoglycemia in infancy.

BACKGROUND: Congenital hyperinsulinism (CHI) is characterized by profound hypoglycaemia caused by inappropriate insulin secretion. CHI is a heterogeneous disorder with at least 2 histologic lesions and several implicated genes. If CHI is caused by a focal lesion, elective surgery is the only treatment because it leads to complete recovery without diabetes; on the contrary, diffuse CHI can only be cured by near-total pancreatectomy, and medical treatment, if efficient, is preferable. It is therefore mandatory to distinguish the 2 forms of CHI, and the surgeon has to fullfill his role in the multidisciplinary team that deals with CHI. METHODS: A total of 134 patients with CHI were investigated both radiologically and with molecular biology. Pathology was the only proof of focal or diffuse lesions, and the pancreatic tissue could be studied by electrophysiology (Katp and Ca channels) and gene study. RESULTS: In 59 infants with CHI, a focal lesion was suspected by radiology and proved by extemporaneous pathology; partial pancreatectomy (33 tail +/- body, 19 head, 5 isthmus resections) was performed, and molecular biology and histochemistry confirmed the genetic lesion specific to the focal disease; 75 near-total pancreatectomies were necessary in diffuse disease to prevent brain damage. CONCLUSIONS: CHI is a severe brain-threatening disease. Surgery is indicated in all focal diseases, providing they are diagnosed preoperatively. In diffuse disease with resistance to medical treatment, near-total pancreatectomy is a last resort option that hopefully will be improved in the future with culture of beta cells and genetic modification of the beta cell disease before autograft.

ATP-Binding Cassette Transporters↗

Anatomical and functional brain imaging evidence of lenticulo-insular anomalies in Smith Magenis syndrome.

Smith Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion of chromosome 17p11.2. The neurobehavioral phenotype of SMS includes mental retardation, speech delay, hyperactivity, attention deficit, decreased sensitivity to pain, self-injury, aggressive behavior and sleep disturbance. Therefore, we performed anatomical and functional brain imaging studies in five SMS boys. Anatomical magnetic resonance imaging (MRI) was analyzed using optimized voxel-based morphometry (VBM). This method can detect structural anomalies not apparent on visual inspection of the scans. Two comparison groups with similar mean age were studied: Group A with 12 healthy control children and Group B with 5 children with idiopathic mental retardation. In addition, positron emission tomography (PET) and water-labeled method were used to investigate a putative localized brain dysfunction in SMS. The control group was composed of mentally retarded children (Group B). A significant bilateral decrease of grey matter concentration was detected in the insula and lenticular nucleus in SMS children. In addition, a significant hypoperfusion was found in the same regions in SMS. These anatomo-functional evidences of bilateral insulo-lenticular anomalies in SMS are consistent with neurobehavioral symptoms of the disease. The identification of localized brain anomalies in SMS may help in understanding how this well-defined genetic entity can lead to a relatively specific severe neurobehavioral syndrome.

Adolescent↗

Superior temporal sulcus anatomical abnormalities in childhood autism: a voxel-based morphometry MRI study.

The underlying neurobiology of autism, a severe pervasive developmental disorder, remains unknown. Few neocortical brain MRI abnormalities have been reported. Using rest functional brain imaging, two independent studies have described localized bilateral temporal hypoperfusion in children with primary autism. In order to search for convergent evidence of anatomical abnormalities in autistic children, we performed an anatomical MRI study using optimized whole-brain voxel-based morphometry (VBM). High-resolution 3-D T1-weighted MRI data sets were acquired in 21 children with primary autism (mean age 9.3 +/- 2.2 years) and 12 healthy control children (mean age 10.8 +/- 2.7 years). By comparing autistic children to normal children, we found bilaterally significant decreases of grey matter concentration located in superior temporal sulcus (STS) (P < 0.05 corrected, after small volume correction; SVC). Children with autism were also found to have a decrease of white matter concentration located in the right temporal pole and in cerebellum (P < 0.05, corrected) compared to normal children. These results suggest that autism is associated with bilateral anatomical abnormalities localized in the STS and are remarkably consistent with functional hypoperfusion previously reported in children with autism. The multimodal STS areas are involved in highest level of cortical integration of both sensory and limbic information. Moreover, the STS is now recognized as a key cortical area of the "social brain" and is implicated in social perceptual skills that are characteristically impaired in autism. Therefore, the convergent anatomical and functional temporal abnormalities observed in autism may be important in the understanding of brain behavior relationships in this severe developmental disorder.

Adolescent↗

A framework to study the cortical folding patterns.

This paper describes a decade-long research program focused on the variability of the cortical folding patterns. The program has developed a framework of using artificial neuroanatomists that are trained to identify sulci from a database. The framework relies on a renormalization of the brain warping problem, which consists in matching the cortices at the scale of the folds. Another component of the program is the search for the alphabet of the folding patterns, namely, a list of indivisible elementary sulci. The search relies on the study of the cortical folding process using antenatal imaging and on backward simulations of morphogenesis aimed at revealing traces of the embryologic dimples in the mature cortical surface. The importance of sulcal-based morphometry is illustrated by a simple study of the correlates of handedness on asymmetry indices. The study shows for instance that the central sulcus is larger in the dominant hemisphere.

Brain Mapping↗

Dandy-Walker malformation: prenatal diagnosis and prognosis.

INTRODUCTION: The difficulty in prognosticating the clinical and intellectual outcome of fetuses presenting with a Dandy-Walker malformation (DWM) comes from the great variety of cystic, median, and retrocerebellar malformations that probably have nothing in common and the variability of the definitions given to these lesions. In addition, many of these lesions can mimic each other. A correct diagnosis cannot be made without a good quality MRI including sagittal views of the vermis and T2-weighted images. We limited the diagnosis of DWM to those malformations with all of the following features: 1) a large median posterior fossa cyst widely communicating with the fourth ventricle, 2) a small, rotated, raised cerebellar vermis, 3) an upwardly displaced tentorium, 4) an enlarged posterior fossa, 5) antero-laterally displaced but apparently normal cerebellar hemispheres, 6) a normal brain stem. If any one of the previous criteria were not met, the malformation was considered distinct from DWM. MATERIALS AND METHODS: The charts of 26 patients with DWMs (18 females and 8 males; median age 10.5 years) were reviewed retrospectively. The diagnosis of the malformation was made prenatally in 7 children and postnatally in the 19 others. All the patients had both one MRI including axial and sagittal views of the posterior fossa as well as T1- and T2-weighted sequences, and one neuro-psychological investigation. Syndromic DWMs and Dandy Walker variants were excluded from the study. MRIs were reviewed in a blinded manner looking for brain malformation or damage and studying with particular attention the anatomy of the vermis. Systemic malformations were also recorded. Developmental quotient (DQ) and intellectual quotient (IQ) were said to be normal when equal or greater than 85, and low when below this value. Statistical analysis was performed using a Fisher test to analyze the relationship between intellectual performances, vermis anatomy, ventricular size, brain anatomy, and associated malformations. RESULTS. On scrutiny of sagittal T2 sequences, the vermis, although constantly small, rotated, and pushed towards the tentorium presented as two distinct morphologies, leading us to distinguish two groups of patients. In the first group (n=21), the vermis presented with two fissures, three lobes, and a fastigium as in the normal situation. In this particular group, none of the patients had associated brain malformation and all but 2 were functioning normally. One of the 2 retarded children had a fragile X syndrome. The other had a severe periventricular leukomalacia due to prematurity, which, per se, was sufficient to account for mental delay. In the second group (n=5), the vermis was highly malformed, obviously dysplastic, presenting with only one fissure or no fissure at all. It was constantly associated with major brain anomalies, most often a complete corpus callosum agenesis. All the patients in this group were more or less severely retarded. Vermis anatomy in DWMs was statistically correlated to neurological and intellectual outcome. Is the vermis dysplasia responsible, in itself, for this poor outcome? No answer can be given from this series, because retardation was observed in children who always had both a severely dysplastic vermis and other brain malformations. No other patient-related factor was statistically correlated to the outcome, in particular, hydrocephalus and extracerebral malformations. CONCLUSION: We described two types of DWM. The most frequent is characterized by an isolated and partially agenetic vermis. This malformation is compatible with a normal life. The second type consists of a severely abnormally lobulated vermis and associated brain malformation. This malformation is always accompanied by mental retardation.

Brain↗