Publications by authors named "Sébastien Lebon"

27 Publications

  • Page 1 of 1

Pediatric Encephalopathy: Clinical, Biochemical and Cellular Insights into the Role of Gln52 of and for the Dominant Disease.

Cells 2021 Oct 14;10(10). Epub 2021 Oct 14.

Translational Research Center in Oncohaematology, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland.

Heterotrimeric G proteins are immediate transducers of G protein-coupled receptors-the biggest receptor family in metazoans-and play innumerate functions in health and disease. A set of de novo point mutations in and , the genes encoding the α-subunits (Gαo and Gαi1, respectively) of the heterotrimeric G proteins, have been described to cause pediatric encephalopathies represented by epileptic seizures, movement disorders, developmental delay, intellectual disability, and signs of neurodegeneration. Among such mutations, the Gln52Pro substitutions have been previously identified in and . Here, we describe the case of an infant with another mutation in the same site, Gln52Arg. The patient manifested epileptic and movement disorders and a developmental delay, at the onset of 1.5 weeks after birth. We have analyzed biochemical and cellular properties of the three types of dominant pathogenic mutants in the Gln52 position described so far: Gαo[Gln52Pro], Gαi1[Gln52Pro], and the novel Gαo[Gln52Arg]. At the biochemical level, the three mutant proteins are deficient in binding and hydrolyzing GTP, which is the fundamental function of the healthy G proteins. At the cellular level, the mutants are defective in the interaction with partner proteins recognizing either the GDP-loaded or the GTP-loaded forms of Gαo. Further, of the two intracellular sites of Gαo localization, plasma membrane and Golgi, the former is strongly reduced for the mutant proteins. We conclude that the point mutations at Gln52 inactivate the Gαo and Gαi1 proteins leading to aberrant intracellular localization and partner protein interactions. These features likely lie at the core of the molecular etiology of pediatric encephalopathies associated with the codon 52 mutations in /.
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http://dx.doi.org/10.3390/cells10102749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535069PMC
October 2021

Agenesis of the Corpus Callosum with Facial Dysmorphism and Intellectual Disability in Sibs Associated with Compound Heterozygous Variants.

Genes (Basel) 2021 Sep 10;12(9). Epub 2021 Sep 10.

Division of Genetic Medicine, Medicine Department, Lausanne University Hospital (CHUV), University of Lausanne, 1011 Lausanne, Switzerland.

We studied a family in which the first-born child, a girl, had developmental delay, facial dysmorphism, and agenesis of the corpus callosum (ACC). The subsequent pregnancy was interrupted as the fetus was found to be also affected by ACC. Both cases were heterozygous for two variants predicting (Ala635Thr) and (Ser1155AlaTer4) that were shown to be in . variants have been previously associated with moderate to severe developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and dysmorphism in a few individuals, but the pathogenetic mechanisms are not clear yet as patients with both monoallelic and biallelic variants have been observed. Interestingly, one individual has previously been reported with ACC and severe ID in association with biallelic variants. Together with the observations in this family, this suggests that agenesis of the corpus callosum may be part of the phenotypic spectrum associated with variants and that the gene should be included in gene panels to clarify the etiology of ACC both in the prenatal and postnatal setting.
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http://dx.doi.org/10.3390/genes12091397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467522PMC
September 2021

Structural brain abnormalities in epilepsy with myoclonic atonic seizures.

Epilepsy Res 2021 Sep 21;177:106771. Epub 2021 Sep 21.

Pediatric Neurology and Neurorehabilitation Unit, Woman-Mother-Child Department, Lausanne University Hospital and University of Lausanne (CHUV-UNIL), Lausanne, Switzerland. Electronic address:

Objective: Epilepsy with myoclonic atonic seizure (EMAS) occurs in young children with previously normal to subnormal development. The outcome ranges from seizure freedom with preserved cognitive abilities to refractory epilepsy with intellectual disability (ID). Routine brain imaging typically shows no abnormalities. We aimed to compare the brain morphometry of EMAS patients with healthy subjects several years after epilepsy onset, and to correlate it to epilepsy severity and cognitive findings.

Methods: Fourteen EMAS patients (4 females, 5-14 years) and 14 matched healthy controls were included. Patients were classified into three outcome groups (good, intermediate, poor) according to seizure control and cognitive and behavioral functioning. Individual anatomical data (T1-weighted sequence) were processed using the FreeSurfer pipeline. Cortical volume (CV), cortical thickness (CT), local gyrification index (LGI), and subcortical volumes were used for group-comparison and linear regression analyses.

Results: Morphometric comparison between EMAS patients and healthy controls revealed that patients have 1) reduced CV in frontal, temporal and parietal lobes (p = <.001; 0.009 and 0.024 respectively); 2) reduced CT and LGI in frontal lobes (p = 0.036 and 0.032 respectively); and 3) a neat cerebellar volume reduction (p = 0.011). Neither the number of anti-seizure medication nor the duration of epilepsy was related to cerebellar volume (both p > 0.62). Poor outcome group was associated with lower LGI. Patients in good and intermediate outcome groups had a comparable LGI to their matched healthy controls (p > 0.27 for all lobes).

Conclusions: Structural brain differences were detectable in our sample of children with EMAS, mainly located in the frontal lobes and cerebellum. These findings are similar to those found in patients with genetic/idiopathic generalized epilepsies. Outcome groups correlated best with LGI. Whether these anatomical changes reflect genetically determined abnormal neuronal networks or a consequence of sustained epilepsy remains to be solved with prospective longitudinal studies.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106771DOI Listing
September 2021

Exposure to alirocumab during the first trimester of pregnancy: A case report.

Birth Defects Res 2021 Sep 8;113(15):1156-1160. Epub 2021 Jun 8.

Service of Endocrinology, Diabetes and Metabolism, Department of Medicine, Lausanne University Hospital & University of Lausanne, Lausanne, Switzerland.

Background: Familial hypercholesterolemia can be efficiently treated with combined lipid-lowering drugs. Lipid-lowering drugs are usually withdrawn for pregnancy and breastfeeding, ideally preconception, followed by lipid apheresis, however, careful plans can be precipitated due to unexpected pregnancy.

Case: A 28-year old woman with familial hypercholesterolemia due to heterozygous LDLR mutations had an LDL-cholesterol level at 14.6 mmol/L and Lp(a) at 1150 mg/L. She required a three-vessel coronary artery bypass graft, drug-eluting stents, rosuvastatin, ezetimibe, and alirocumab at maximal dosage. Contraception was advised during the following 12 months, with a planned drug withdrawal to bridge with lipid apheresis, such as the direct adsorption of lipoproteins (DALI). However, an unplanned pregnancy required an abrupt stop of all oral medications at six gestational weeks, except for aspirin. Lipid apheresis controlled LDL-cholesterol in the range of 4.9-7.9 mmol/L (before DALI session) to 1.2-3.2 mmol/L (after DALI session). Later, the regular pregnancy ultrasounds highlighted an isolated agenesis of the corpus callosum later confirmed by magnetic resonance imaging.

Conclusions: A causal link between the early pregnancy exposure to PCSK9 inhibitors (or statins and ezetimibe taken concomitantly) and the observed complete agenesis of the corpus callosum seems unlikely in this case. Guidelines do not specifically recommend preconception measures to lower fetal and/or maternal risks of patients with severe FH considering pregnancy. We argue that lipid apheresis and other measures should be discussed with women with FH and maternity project on an individual basis, until pharmacoepidemiology studies assessing the safety of PCSK9 inhibitors in pregnancy are available.
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http://dx.doi.org/10.1002/bdr2.1930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453706PMC
September 2021

LBSL: Case Series and DARS2 Variant Analysis in Early Severe Forms With Unexpected Presentations.

Neurol Genet 2021 Apr 2;7(2):e559. Epub 2021 Feb 2.

Department of Child Neurology, Emma Childrens Hospital, Amsterdam University Medical Centers, Vrije Universiteit and Amsterdam Neuroscience, The Netherlands (M.D.S., T.E.M.A.); Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Italy (S.F., C.D., P.G.); Area di Ricerca Genetica e Malattie Rare (E.B.), Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy; Laboratory of Oncology and Molecular Genetics (K.A.), Clínica las Condes, Santiago, Chile; Department of Pediatric Neurology (C.C.), Clínica Las Condes, Santiago, Chile; Division of Child Neurology (P.T.), Department of Neurology, Istanbul Faculty of Medicine, Turkey; Department of Paediatrics (C.A.S.), Royal Childrens Hospital, Murdoch Childrens Research Institute and University of Melbourne, Victoria, Australia; Pediatric Neurology (C.E.E.), Radboud University Medical Center, Amalia Childrens Hospital, Nijmegen, The Netherlands; Department of Pediatrics (A.S.-V.), University of South Florida, Tampa; Unit of Pediatric Neurology and Neurorehabilitation (S.L.), Department WomanMother-Child, Lausanne University Hospital, Switzerland; Community Pediatrics, Royal Berkshire Hospital, Reading (S.H.), United Kingdom; Neuropediatric Department (T.S.-M.), Childrens Hospital, Luzern, Switzerland; Unit of Neurorehabilitation (G.V.), Department of Neurosciences, Bambino Gesù Children's Research Hospital, IRCCS, Rome, Italy; Paediatric Neurology (G.C.), Nottingham Childrens Hospital, United Kingdom; PEDEGO Research Unit (E.R.), Medical Research Center and Department of Clinical Genetics, University of Oulu and Oulu University Hospital, Finland; Radiology (C.O.), Clínica las Condes, Santiago, Chile; Unit of Neuromuscular and Neurodegenerative Disorders (E.S.B), Area di Ricerca Genetica e Malattie Rare and Department of Neurosciences, Bambino Gesù Children's Research Hospital, IRCCS, Rome, Italy; and Department of Child Neurology (M.S.v.d.K.), Emma Childrens Hospital and Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, the Netherlands.

Objective: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is regarded a relatively mild leukodystrophy, diagnosed by characteristic long tract abnormalities on MRI and biallelic variants in , encoding mitochondrial aspartyl-tRNA synthetase (mtAspRS). variants in LBSL are almost invariably compound heterozygous; in 95% of cases, 1 is a leaky splice site variant in intron 2. A few severely affected patients, still fulfilling the MRI criteria, have been described. We noticed highly unusual MRI presentations in 15 cases diagnosed by WES. We examined these cases to determine whether they represent consistent novel LBSL phenotypes.

Methods: We reviewed clinical features, MRI abnormalities, and gene variants and investigated the variants' impact on mtAspRS structure and mitochondrial function.

Results: We found 2 MRI phenotypes: early severe cerebral hypoplasia/atrophy (9 patients, group 1) and white matter abnormalities without long tract involvement (6 patients, group 2). With antenatal onset, microcephaly, and arrested development, group 1 patients were most severely affected. variants were severer than for classic LBSL and severer for group 1 than group 2. All missense variants hit mtAspRS regions involved in tRNA binding, aspartyl-adenosine-5'-monophosphate binding, and/or homodimerization. Missense variants expressed in the yeast ortholog showed severely affected mitochondrial function.

Conclusions: variants are associated with highly heterogeneous phenotypes. New MRI presentations are profound cerebral hypoplasia/atrophy and white matter abnormalities without long tract involvement. Our findings have implications for diagnosis and understanding disease mechanisms, pointing at dominant neuronal/axonal involvement in severe cases. In line with this conclusion, activation of biallelic null alleles in conditional transgenic mice leads to massive neuronal apoptosis.
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http://dx.doi.org/10.1212/NXG.0000000000000559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105885PMC
April 2021

Biallelic variants in cause a severe neurodevelopmental disorder with microcephaly, bilateral cataract, epilepsy and simplified gyration.

J Med Genet 2021 Jan 4. Epub 2021 Jan 4.

Medical Genetics Laboratory, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Background: Next-generation sequencing, combined with international pooling of cases, has impressively enhanced the discovery of genes responsible for Mendelian neurodevelopmental disorders, particularly in individuals affected by clinically undiagnosed diseases. To date, biallelic missense variants in gene, encoding a Krüppel-type zinc-finger protein, have been reported in three families with non-syndromic intellectual disability.

Methods: Here, we describe five individuals from four unrelated families with an undiagnosed neurodevelopmental disorder in which we performed exome sequencing, on a combination of trio-based (4 subjects) or single probands (1 subject).

Results: We identified five patients from four unrelated families with homozygous variants by whole exome sequencing. Four had variants resulting in truncation of ZNF526; they were affected by severe prenatal and postnatal microcephaly (ranging from -4 SD to -8 SD), profound psychomotor delay, hypertonic-dystonic movements, epilepsy and simplified gyral pattern on MRI. All of them also displayed bilateral progressive cataracts. A fifth patient had a homozygous missense variant and a slightly less severe disorder, with postnatal microcephaly (-2 SD), progressive bilateral cataracts, severe intellectual disability and unremarkable brain MRI.Mutant zebrafish larvae had notable malformations of the eye and central nervous system, resembling findings seen in the human holoprosencephaly spectrum.

Conclusion: Our findings support the role of biallelic variants in a complex neurodevelopmental disorder, primarily affecting brain and eyes, resulting in severe microcephaly, simplified gyral pattern, epileptic encephalopathy and bilateral cataracts.
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http://dx.doi.org/10.1136/jmedgenet-2020-107430DOI Listing
January 2021

Basal Ganglia Dysmorphism in Patients With Aicardi Syndrome.

Neurology 2021 03 4;96(9):e1319-e1333. Epub 2020 Dec 4.

From the Department of Brain and Behavioural Neurosciences (S.M., A.P., M. Formica, S.O.) and Department of Public Health Experimental and Forensic Medicine, Biostatistic and Clinical Epidemiology Unit (P. Borrelli), University of Pavia; Pediatric Neurology Unit (S.M., M. Mastrangelo, P.V.), V. Buzzi Children's Hospital, Milan; Department of Neuroradiology (A.P.), Child Neurology and Psychiatry Unit (R.B., V.D.G., S.O.), and Department of Internal Medicine and Therapeutics, Member of the ERN EpiCARE, University of Pavia and Clinical Trial Center (E.P.), IRCCS Mondino Foundation Pavia; Neuroimaging Lab (F.A.) and Neuropsychiatry and Neurorehabilitation Unit (R.R.), Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco; Child Neuropsychiatric Unit (P.A., L.G.), Civilian Hospital, Brescia; Scientific Institute (P. Bonanni, A.D., E.O.), IRCCS E. Medea, Epilepsy and Clinical Neurophysiology Unit, Conegliano, Treviso; UOC Child Neuropsychiatry (B.D.B., F.D.), Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Italy; Département de Neurologie Pédiatrique (N.D.), Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Belgium; AdPueriVitam (O.D.), Antony; Service d'Explorations Fonctionnelles (S.G.), Centre de Médecine du Sommeil, l'Hôpital Àntoine Béclère, AP-HP, Clamart; Pediatrics Departement (S.G.), André-Grégoire Hospital, Centre Hospitalier Inter Communal, Montreuil, France; Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Neuroscience Department (R.G., M. Montomoli, M.C.) and Radiology (M. Mortilla), A. Meyer Children's Hospital, Member of the ERN EpiCARE, University of Florence; IRCCS Stella Maris Foundation (R.G.), Pisa; Child Neuropsychiatry Unit, Epilepsy Center (F.L.B., A.V.), San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Milan; Child Neurology, NESMOS Department (P.P.), Faculty of Medicine & Psychology, Sant'Andrea Hospital, Sapienza University, Rome; Department of Neuroradiology (L.P.), Pediatric Neuroradiology Section, ASST Spedali Civili, Brescia; Pediatric Neuroradiology Unit (M.S.), IRCCS Istituto Giannina Gaslini, Genova; Neurology Unit, Department of Neuroscience, Member of the ERN EpiCARE (F.V.), Oncological Neuroradiology Unit, Department of Imaging, IRCCS (G.C.), and Department of Neuroscience and Neurorehabilitation (A.F.), Bambino Gesù Children's Hospital, Rome, Italy; Institut Imagine (N.B.-B.), Université Paris Descartes-Sorbonne Paris Cités; Pediatric Neurology (N.B.-B., I.D.), Necker Enfants Malades Hospital, Member of the ERN EpiCARE, Assistance Publique-Hôpitaux de Paris; INSERM UMR-1163 (N.B.-B., A. Arzimanoglou), Embryology and Genetics of Congenital Malformations, France; UOC Neurochirurgia (A. Accogli, V.C.), Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa (F.Z.), and Laboratory of Neurogenetics and Neuroscience, IRCCS (F.Z.), Istituto Giannina Gaslini, Genoa, Italy; Neurochirurgie Pédiatrique (M.B.), Hôpital NEM, Paris, France; Centre Médico-Chirurgical des Eaux-Vives (V.C.-V.), Swiss Medical Network, Genève, Switzerland; Neuroradiology Unit (L.C.) and Developmental Neurology Unit (S.D.), Foundation IRCCS C. Besta Neurological Institute, Milan; Service de Génétique (M.D.-F.), AMH2, CHU Reims, UFR de Médecine, Reims, France; Epilepsy Centre-Clinic of Nervous System Diseases (G.d.), Riuniti Hospital, Foggia, Italy; MediClubGeorgia Co Ltd (N.E.), Tbilisi, Georgia; Epilepsy Center (N.E.), Medical Center, Faculty of Medicine, University of Freiburg, Germany; Child and Adolescence Neurology and Psychiatry Unit (E. Fazzi), ASST Civil Hospital, Department of Clinical and Experimental Sciences, University of Brescia; Child Neurology Department (E. Fiorini), Verona, Italy; Service de Genetique Clinique (M. Fradin, P.L., C.Q.), CLAD-Ouest, Hospital Sud, Rennes, France; Child Neurology Unit, Pediatric Department (C.F., C.S.), Azienda USL-IRCCS di Reggio Emilia; Department of Pediatric Neuroscience (T.G., R.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Member of the ERN EpiCARE, Milan, Italy; Department of Epilepsy Genetics and Personalized Treatment (K.M.J., R.S.M.), The Danish Epilepsy Centre, Dianalund; Institute for Regional Health Services (K.M.J., R.S.M.), University of Southern Denmark, Odense; Unit of Pediatric Neurology and Pediatric Neurorehabilitation (S.L.), Woman-Mother-Child Department, Lausanne University Hospital CHUV, Switzerland; Unit of Neuroradiology (D.M.), Fondazione CNR/Regione Toscana G. Monasterio, Pisa; Pediatric Neurology Unit and Epilepsy Center (E.R., A.R.), Fatebenefratelli Hospital, Milan, Italy; KJF Klinik Josefinum GmbH (C.U.), Klinik für Kinder und Jugendliche, Neuropädiatrie, Augsburg, Germany; Department of Paediatric Clinical Epileptology, Sleep Disorders and Functional Neurology (A. Arzimanoglou), University Hospitals of Lyon, Coordinator of the ERN EpiCARE, France; and Pediatric Epilepsy Unit, Child Neurology Department (P.V.), Hospital San Juan de Dios, Member of the ERN EpiCARE and Universitat de Barcelona, Spain.

Objective: Aiming to detect associations between neuroradiologic and EEG evaluations and long-term clinical outcome in order to detect possible prognostic factors, a detailed clinical and neuroimaging characterization of 67 cases of Aicardi syndrome (AIC), collected through a multicenter collaboration, was performed.

Methods: Only patients who satisfied Sutton diagnostic criteria were included. Clinical outcome was assessed using gross motor function, manual ability, and eating and drinking ability classification systems. Brain imaging studies and statistical analysis were reviewed.

Results: Patients presented early-onset epilepsy, which evolved into drug-resistant seizures. AIC has a variable clinical course, leading to permanent disability in most cases; nevertheless, some cases presented residual motor abilities. Chorioretinal lacunae were present in 86.56% of our patients. Statistical analysis revealed correlations between MRI, EEG at onset, and clinical outcome. On brain imaging, 100% of the patients displayed corpus callosum malformations, 98% cortical dysplasia and nodular heterotopias, and 96.36% intracranial cysts (with similar rates of 2b and 2d). As well as demonstrating that posterior fossa abnormalities (found in 63.63% of cases) should also be considered a common feature in AIC, our study highlighted the presence (in 76.36%) of basal ganglia dysmorphisms (never previously reported).

Conclusion: The AIC neuroradiologic phenotype consists of a complex brain malformation whose presence should be considered central to the diagnosis. Basal ganglia dysmorphisms are frequently associated. Our work underlines the importance of MRI and EEG, both for correct diagnosis and as a factor for predicting long-term outcome.

Classification Of Evidence: This study provides Class II evidence that for patients with AIC, specific MRI abnormalities and EEG at onset are associated with clinical outcomes.
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http://dx.doi.org/10.1212/WNL.0000000000011237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055324PMC
March 2021

Sultiame pharmacokinetic profile in plasma and erythrocytes after single oral doses: A pilot study in healthy volunteers.

Pharmacol Res Perspect 2020 02;8(1):e00558

Service of Clinical Pharmacology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.

A pilot study was conducted aiming at specifying sultiame's pharmacokinetic profile, completed by in vitro assays evaluating the intraerythrocytic transfer of sultiame and by a pharmacokinetic model assessing its distribution. Single oral doses of sultiame (Ospolot 50, 100, and 200 mg) were administered in open-label to four healthy volunteers. Serial plasma, whole blood, and urine samples were collected. A spiking experiment was also performed to characterize sultiame's exchanges between plasma and erythrocytes in vitro. Pharmacokinetic parameters were evaluated using standard noncompartmental calculations and nonlinear mixed-effect modeling. The plasma maximal concentrations (C ) showed striking nonlinear disposition of sultiame, with a 10-fold increase while doses were doubled. Conversely, whole blood C increased less than dose proportionally while staying much higher than in plasma. Quick uptake of sultiame into erythrocytes observed in vivo was confirmed in vitro, with minimal efflux. A two-compartment model with first-order absorption, incorporating a saturable ligand to receptor binding, described the data remarkably well, indicating apparent plasma clearance of 10.0 L/h (BSV: 29%) and distribution volume of 64.8 L; saturable uptake into an intracellular compartment of 3.3 L with a maximum binding capacity of 111 mg accounted for nonlinearities observed in plasma and whole blood concentrations. Pharmacokinetic characteristics of sultiame are reported, including estimates of clearance and volume of distribution that were so far unpublished. The noticeable nonlinearity in sultiame disposition should be taken into account for the design of future studies and the interpretation of therapeutic drug monitoring results.
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http://dx.doi.org/10.1002/prp2.558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986439PMC
February 2020

Clinical Reasoning: Rapidly progressive gait disorder and cranial nerves involvement in a 9-year-old boy.

Neurology 2020 01;94(3):e330-e334

From the Division of Pediatrics (A.L., J.-B.A.), Pediatric Hematology Oncology Unit (C.A., M.B.-P.), Paediatric Infectious Diseases and Vaccinology Unit (S.A.), and Unit of Pediatric Neurology and Neurorehabilitation (C.P., E.R.-P., S.L.), Department Woman-Mother-Child, University Institute of Pathology (J.-P.B.), Department of Clinical Neurosciences, Service of Neurosurgery (M.M.), and Infectious Disease Service, Department of Medicine (S.A.), Lausanne University Hospital, Switzerland.

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http://dx.doi.org/10.1212/WNL.0000000000008826DOI Listing
January 2020

Childhood neurodegeneration associated with a specific UBTF variant: a new case report and review of the literature.

BMC Neurol 2020 Jan 13;20(1):17. Epub 2020 Jan 13.

Department woman-mother-child, Unit of Paediatric Neurology and Neurorehabilitation, Lausanne University Hospital (CHUV), Rue du Bugnon 21, 1011, Lausanne, Switzerland.

Background: A new monogenic neurodegenerative disease affecting ribosomal metabolism has recently been identified in association with a monoallelic UBTF putative gain of function variant (NM_001076683.1:c.628G>A, hg19). Phenotype is consistent among these probands with progressive motor, cognitive, and behavioural regression in early to middle childhood.

Case Presentation: We report on a child with this monoallelic UBTF variant who presented with progressive disease including regression, episodes of subacute deterioration during febrile illnesses and a remarkable EEG pattern with a transient pattern of semi-periodic slow waves.

Conclusions: This case further supports the phenotype-genotype correlation of neurodegeneration associated with UBTF c.628G>A. Moreover, it brings new insights into the clinical features and EEG that could possibly serve as diagnostic markers of this otherwise nonspecific phenotype.
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http://dx.doi.org/10.1186/s12883-019-1586-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958716PMC
January 2020

Midazolam as a first-line treatment for neonatal seizures: Retrospective study.

Pediatr Int 2018 May;60(5):498-500

Unit of Pediatric Neurology and Neurorehabilitation, Mother-Woman-Child Department, Lausanne University Hospital, Lausanne, Switzerland.

Midazolam is commonly used to treat refractory seizures in newborns and as a first-line anti-epileptic drug in children. Its use as first-line treatment of neonatal seizures has not been investigated so far. We retrospectively studied the tolerability of midazolam in 72 newborn infants who received i.v. or i.n. midazolam as first-line treatment for seizures. No major side-effect exclusively due to midazolam was reported. The i.n. route was used for 20 patients (27.8%). Effectiveness could not be formally evaluated due to the absence of systematic electroencephalogram recording while midazolam was administered. In conclusion, midazolam was well-tolerated as a first-line abortive emergency treatment of neonatal seizure. The i.n. route offers a useful alternative to i.v. phenobarbital or phenytoin in emergency settings.
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http://dx.doi.org/10.1111/ped.13554DOI Listing
May 2018

[Pediatrics - New classification of seizures and epilepsies].

Rev Med Suisse 2018 Jan;14(588-589):74-75

Unité de neuropédiatrie et neuroréhabilitation pédiatrique, Département femme- mère-enfant, CHUV, 1011 Lausanne.

The International League Against Epilepsy published a new classification of epileptic seizures and epilepsies. It is more transparent and important notions like etiologies and comorbities have been added. The identification of seizures, epilepsies then epilepsy syndromes constitutes the three steps of this classification.
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January 2018

Autosomal recessive primary microcephaly due to ASPM mutations: An update.

Hum Mutat 2018 03 16;39(3):319-332. Epub 2018 Jan 16.

Service de pédiatrie, Hôpital Nord Ouest-Villefranche, Gleize, France.

Autosomal recessive microcephaly or microcephaly primary hereditary (MCPH) is a genetically heterogeneous neurodevelopmental disorder characterized by a reduction in brain volume, indirectly measured by an occipitofrontal circumference (OFC) 2 standard deviations or more below the age- and sex-matched mean (-2SD) at birth and -3SD after 6 months, and leading to intellectual disability of variable severity. The abnormal spindle-like microcephaly gene (ASPM), the human ortholog of the Drosophila melanogaster "abnormal spindle" gene (asp), encodes ASPM, a protein localized at the centrosome of apical neuroprogenitor cells and involved in spindle pole positioning during neurogenesis. Loss-of-function mutations in ASPM cause MCPH5, which affects the majority of all MCPH patients worldwide. Here, we report 47 unpublished patients from 39 families carrying 28 new ASPM mutations, and conduct an exhaustive review of the molecular, clinical, neuroradiological, and neuropsychological features of the 282 families previously reported (with 161 distinct ASPM mutations). Furthermore, we show that ASPM-related microcephaly is not systematically associated with intellectual deficiency and discuss the association between the structural brain defects (strong reduction in cortical volume and surface area) that modify the cortical map of these patients and their cognitive abilities.
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http://dx.doi.org/10.1002/humu.23381DOI Listing
March 2018

Periinsular anterior quadrantotomy: technical note.

J Neurosurg Pediatr 2018 02 8;21(2):124-132. Epub 2017 Dec 8.

1Department of Neurosurgery and.

Refractory frontal lobe epilepsy has been traditionally treated through a frontal lobectomy. A disconnective technique may allow similar seizure outcomes while avoiding the complications associated with large brain resections. The aim of this study was to describe a new technique of selective disconnection of the frontal lobe that can be performed in cases of refractory epilepsy due to epileptogenic foci involving 1 frontal lobe (anterior to the motor cortex), with preservation of motor function. In addition to the description of the technique, an illustrative case is also presented. This disconnective procedure is divided into 4 steps: the suprainsular window, the anterior callosotomy, the intrafrontal disconnection, and the frontobasal disconnection. The functional neuroanatomy is analyzed in detail for each step of the surgery. It is important to perform cortical and subcortical electrophysiological mapping to guide this disconnective procedure and identify eloquent cortices and intact neural pathways. The authors describe the case of a 9-year-old boy who presented with refractory epilepsy due to epileptogenic foci localized to the right frontal lobe. MRI confirmed the presence of a focal cortical dysplasia of the right frontal lobe. A periinsular anterior quadrant disconnection (quadrantotomy) was performed. The postoperative period was uneventful, and the patient was in Engel seizure outcome Class I at the 3-year follow-up. A significant cognitive gain was observed during follow-up. Periinsular anterior quadrantotomy may thus represent a safe technique to efficiently treat refractory epilepsy when epileptogenic foci are localized to 1 frontal lobe while preserving residual motor functions.
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http://dx.doi.org/10.3171/2017.8.PEDS17339DOI Listing
February 2018

Prenatal Brainstem Disruptions: Small Lesions-Big Problems.

Neuropediatrics 2017 10 1;48(5):350-355. Epub 2017 Jun 1.

Division of Pediatric Radiology and Pediatric Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.

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http://dx.doi.org/10.1055/s-0037-1603516DOI Listing
October 2017

Perinatal arterial ischemic stroke related to carotid artery occlusion.

Eur J Paediatr Neurol 2016 Jul 16;20(4):639-48. Epub 2016 Mar 16.

French Centre for Pediatric Stroke, University Hospital Centre of Saint-Etienne, 42055 Saint-Etienne Cedex 2, France.

Background: The aetiology of perinatal arterial ischemic stroke remains speculative. It is however widely accepted that the aetiology is multifactorial, involving various maternal, placental, foetal and neonatal risk factors. A resulting thromboembolic process is hypothesized and the placenta identified as the most plausible source. An arteriopathy, as observed in a significant proportion of childhood ischemic stroke, is thought to be rare.

Methods: We report here five cases of perinatal stroke that differ from the vast majority by documented carotid occlusion, and add eleven other similar cases from the literature.

Results: In the majority, an intraluminal thrombus of placental origin is the most probable hypothesis, while in the remaining ones, one can reasonably presume a direct vessel wall injury related to a traumatic delivery, yet generally unproven by imaging.

Conclusion: We hypothesize that most of these cases share similar pathophysiology with the more common perinatal arterial ischemic stroke but differ by a persistent identified thrombus in the carotid artery at the time of first imaging, leading to a more severe and extended ischemic damage responsible for an adverse neurological outcome.
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http://dx.doi.org/10.1016/j.ejpn.2016.03.003DOI Listing
July 2016

Defining the Effect of the 16p11.2 Duplication on Cognition, Behavior, and Medical Comorbidities.

JAMA Psychiatry 2016 Jan;73(1):20-30

Service de Génétique Médicale, Faculté de Médecine, Centre Hospitalier Universitaire (CHU) Nantes, Institut National de la Santé et de la Recherche Medicale (INSERM) Unités Mixtes de Recherche 957, Nantes, France26Service de Génétique Médicale, CHU de Bor.

Importance: The 16p11.2 BP4-BP5 duplication is the copy number variant most frequently associated with autism spectrum disorder (ASD), schizophrenia, and comorbidities such as decreased body mass index (BMI).

Objectives: To characterize the effects of the 16p11.2 duplication on cognitive, behavioral, medical, and anthropometric traits and to understand the specificity of these effects by systematically comparing results in duplication carriers and reciprocal deletion carriers, who are also at risk for ASD.

Design, Setting, And Participants: This international cohort study of 1006 study participants compared 270 duplication carriers with their 102 intrafamilial control individuals, 390 reciprocal deletion carriers, and 244 deletion controls from European and North American cohorts. Data were collected from August 1, 2010, to May 31, 2015 and analyzed from January 1 to August 14, 2015. Linear mixed models were used to estimate the effect of the duplication and deletion on clinical traits by comparison with noncarrier relatives.

Main Outcomes And Measures: Findings on the Full-Scale IQ (FSIQ), Nonverbal IQ, and Verbal IQ; the presence of ASD or other DSM-IV diagnoses; BMI; head circumference; and medical data.

Results: Among the 1006 study participants, the duplication was associated with a mean FSIQ score that was lower by 26.3 points between proband carriers and noncarrier relatives and a lower mean FSIQ score (16.2-11.4 points) in nonproband carriers. The mean overall effect of the deletion was similar (-22.1 points; P < .001). However, broad variation in FSIQ was found, with a 19.4- and 2.0-fold increase in the proportion of FSIQ scores that were very low (≤40) and higher than the mean (>100) compared with the deletion group (P < .001). Parental FSIQ predicted part of this variation (approximately 36.0% in hereditary probands). Although the frequency of ASD was similar in deletion and duplication proband carriers (16.0% and 20.0%, respectively), the FSIQ was significantly lower (by 26.3 points) in the duplication probands with ASD. There also were lower head circumference and BMI measurements among duplication carriers, which is consistent with the findings of previous studies.

Conclusions And Relevance: The mean effect of the duplication on cognition is similar to that of the reciprocal deletion, but the variance in the duplication is significantly higher, with severe and mild subgroups not observed with the deletion. These results suggest that additional genetic and familial factors contribute to this variability. Additional studies will be necessary to characterize the predictors of cognitive deficits.
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http://dx.doi.org/10.1001/jamapsychiatry.2015.2123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5894477PMC
January 2016

Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients.

Am J Med Genet A 2016 Jan 30;170A(1):116-29. Epub 2015 Sep 30.

Service de Génétique Médicale, CHU de Rouen, France.

Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between >+2SD in five patients and <-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment.
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http://dx.doi.org/10.1002/ajmg.a.37384DOI Listing
January 2016

Early-onset encephalopathy with epilepsy associated with a novel splice site mutation in SMC1A.

Am J Med Genet A 2015 Dec 11;167A(12):3076-81. Epub 2015 Sep 11.

Inserm, Institut Cochin, Paris, France.

We report on the clinical and molecular characterization of a female patient with early-onset epileptic encephalopathy, who was found to carry a de novo novel splice site mutation in SMC1A. This girl shared some morphologic and anthropometric traits described in patients with clinical diagnosis of Cornelia de Lange syndrome and with SMC1A mutation but also has severe encephalopathy with early-onset epilepsy. In addition, she had midline hand stereotypies and scoliosis leading to the misdiagnosis of a Rett overlap syndrome. Molecular studies found a novel de novo splice site mutation (c.1911 + 1G > T) in SMC1A. This novel splice mutation was associated with an aberrantly processed mRNA that included intron 11 of the gene. Moreover, quantitative approach by RT-PCR showed a severe reduction of the SMC1A transcript suggesting that this aberrant transcript may be unstable and degraded. Taken together, our data suggest that the phenotype may be due to a loss-of-function of SMC1A in this patient. Our findings suggest that loss-of-function mutations of SMC1A may be associated with early-onset encephalopathy with epilepsy.
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http://dx.doi.org/10.1002/ajmg.a.37364DOI Listing
December 2015

When should clinicians search for GLUT1 deficiency syndrome in childhood generalized epilepsies?

Eur J Paediatr Neurol 2015 Mar 11;19(2):170-5. Epub 2014 Dec 11.

Pediatric Neurology and Neurorehabilitation Unit, Department of Pediatrics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Unlabelled: GLUT1 deficiency (GLUT1D) has recently been identified as an important cause of generalized epilepsies in childhood. As it is a treatable condition, it is crucial to determine which patients should be investigated.

Methods: We analyzed SLC2A1 for mutations in a group of 93 unrelated children with generalized epilepsies. Fasting lumbar puncture was performed following the identification of a mutation. We compared our results with a systematic review of 7 publications of series of patients with generalized epilepsies screened for SLC2A1 mutations.

Results: We found 2/93 (2.1%) patients with a SLC2A1 mutation. One, carrying a novel de novo deletion had epilepsy with myoclonic-atonic seizures (MAE), mild slowing of head growth, choreiform movements and developmental delay. The other, with a paternally inherited missense mutation, had childhood absence epilepsy with atypical EEG features and paroxysmal exercise-induced dyskinesia (PED) initially misdiagnosed as myoclonic seizures. Out of a total of 1110 screened patients with generalized epilepsies from 7 studies, 2.4% (29/1110) had GLUT1D. This rate was higher (5.6%) among 303 patients with early onset absence epilepsy (EOAE) from 4 studies. About 50% of GLUT1D patients had abnormal movements and 41% a family history of seizures, abnormal movements or both.

Conclusion: GLUT1D is most likely to be found in MAE and in EOAE. The probability of finding GLUT1D in the classical idiopathic generalized epilepsies is very low. Pointers to GLUT1D include an increase in seizures before meals, cognitive impairment, or PED which can easily be overlooked.
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http://dx.doi.org/10.1016/j.ejpn.2014.11.009DOI Listing
March 2015

16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy.

Hum Mol Genet 2014 Nov 16;23(22):6069-80. Epub 2014 Jun 16.

Division of Genetic Medicine, University of Washington, Seattle, Washington, USA.

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65,046 European population controls (5/393 cases versus 32/65,046 controls; Fisher's exact test P = 2.83 × 10(-6), odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10(-4)). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical RE.
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http://dx.doi.org/10.1093/hmg/ddu306DOI Listing
November 2014

When is a child with status epilepticus likely to have Dravet syndrome?

Epilepsy Res 2014 May 12;108(4):740-7. Epub 2014 Mar 12.

Pediatric Neurology, Child and Adolescent Department, University Hospitals, Geneva, Switzerland. Electronic address:

Purpose: To identify clinical risk factors for Dravet syndrome (DS) in a population of children with status epilepticus (SE).

Material And Methods: Children aged between 1 month and 16 years with at least one episode of SE were referred from 6 pediatric neurology centers in Switzerland. SE was defined as a clinical seizure lasting for more than 30min without recovery of normal consciousness. The diagnosis of DS was considered likely in previously healthy patients with seizures of multiple types starting before 1 year and developmental delay on follow-up. The presence of a SCN1A mutation was considered confirmatory for the diagnosis. Data such as gender, age at SE, SE clinical presentation and recurrence, additional seizure types and epilepsy diagnosis were collected. SCN1A analyses were performed in all patients, initially with High Resolution Melting Curve Analysis (HRMCA) and then by direct sequencing on selected samples with an abnormal HRMCA. Clinical and genetic findings were compared between children with DS and those with another diagnosis, and statistical methods were applied for significance analysis.

Results: 71 children with SE were included. Ten children had DS, and 61 had another diagnosis. SCN1A mutations were found in 12 of the 71 patients (16.9%; ten with DS, and two with seizures in a Generalized Epilepsy with Febrile Seizures+(GEFS+) context). The median age at first SE was 8 months in patients with DS, and 41 months in those with another epilepsy syndrome (p<0.001). Nine of the 10 DS patients had their initial SE before 18 months. Among the 26 patients aged 18 months or less at initial SE, the risk of DS was significantly increased for patients with two or more episodes (56.3%), as compared with those who had only one episode (0.0%) (p=0.005).

Conclusion: In a population of children with SE, patients most likely to have DS are those who present their initial SE episode before 18 months, and who present with recurrent SE episodes.
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http://dx.doi.org/10.1016/j.eplepsyres.2014.02.019DOI Listing
May 2014

[Genetics of childhood epilepsies: for who? how? why?].

Rev Med Suisse 2014 Jan;10(412-413):110-1

Unité de Neuropédiatrie et Neuroréhabelitation Pédiatrique, CHUV, Lausanne.

Recent advances in genetics led to significant improvement in the field of childhood epilepsies diagnosis and physiopathology. Genetic testing is indicated by geneticist who is himself guided by the pediatric neurological approach. In rare circumstance, genetic etiology affects the clinical management. Cost remains the main limitation. Those new genetic tools are the first step toward a better understanding of seizure mechanism and therefore more efficient treatments.
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January 2014

A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders.

J Med Genet 2012 Oct;49(10):660-8

Service de Génétique Médicale, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Background: The recurrent ~600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders.

Objective: To define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion.

Methods: We collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers and 68 intrafamilial non-carrier controls.

Results: When compared to intrafamilial controls, full scale intelligence quotient (FSIQ) is two standard deviations lower in carriers, and there is no difference between carriers referred for neurodevelopmental disorders and carriers identified through cascade family testing. Verbal IQ (mean 74) is lower than non-verbal IQ (mean 83) and a majority of carriers require speech therapy. Over 80% of individuals exhibit psychiatric disorders including ASD, which is present in 15% of the paediatric carriers. Increase in head circumference (HC) during infancy is similar to the HC and brain growth patterns observed in idiopathic ASD. Obesity, a major comorbidity present in 50% of the carriers by the age of 7 years, does not correlate with FSIQ or any behavioural trait. Seizures are present in 24% of carriers and occur independently of other symptoms. Malformations are infrequently found, confirming only a few of the previously reported associations.

Conclusions: The 16p11.2 deletion impacts in a quantitative and independent manner FSIQ, behaviour and body mass index, possibly through direct influences on neural circuitry. Although non-specific, these features are clinically significant and reproducible. Lastly, this study demonstrates the necessity of studying large patient cohorts ascertained through multiple methods to characterise the clinical consequences of rare variants involved in common diseases.
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http://dx.doi.org/10.1136/jmedgenet-2012-101203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494011PMC
October 2012

[Therapeutic advances in refractory epilepsies in children].

Rev Med Suisse 2012 Feb;8(329):413-4, 416-7

Neuropédiatrie Service des spécialités pédiatriques, Département de l'enfant et de l'adolescent, HUG, 1211 Genève 14.

Epilepsy concerns several thousands of children in Switzerland, and is refractory to classic antiepileptic drugs in an important proportion of cases. This percentage has remained stable, despite a constant production of new antiepileptic molecules. To alleviate this problem, several alternative approaches have been developed these last years. In this article, we present three children who suffer from different forms of pharmacoresistant epilepsy, managed with immunomodulatory or neurosurgical treatments, and we summarize the current knowledge about these therapeutic options.
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February 2012

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis mimicking a primary psychiatric disorder in an adolescent.

J Child Neurol 2012 Dec 8;27(12):1607-10. Epub 2012 Mar 8.

Department of Pediatric Medico-surgical, Pediatric Neurology and Neurorehabilitation Unit, CHUV, Lausanne, Switzerland.

Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis likely has a wider clinical spectrum than previously recognized. This article reports a previously healthy 16-year-old girl who was diagnosed with anti-NMDA receptor encephalitis 3 months after onset of severe depression with psychotic features. She had no neurological manifestations, and cerebral magnetic resonance imaging (MRI) was normal. Slow background on electroencephalogram and an oligoclonal band in the cerebrospinal fluid prompted the search for anti-NMDA receptor antibodies. She markedly improved over time but remained with mild neuropsychological sequelae after a trial of late immunotherapy. Only a high index of suspicion enables recognition of the milder forms of the disease masquerading as primary psychiatric disorders.
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http://dx.doi.org/10.1177/0883073812438099DOI Listing
December 2012

An initial MRI picture of limbic encephalitis in subacute sclerosing panencephalitis.

Eur J Paediatr Neurol 2011 Nov 31;15(6):544-6. Epub 2011 May 31.

Unité de Neurologie et de Neurorehabilitation Pédiatrique, Département Médico-Chirurgical de Pédiatrie, CHUV, Lausanne, Switzerland.

Background: Subacute sclerosing panencephalitis (SSPE) is a rare and severe long-term complication of measles. Hallmarks of this entity include progressive cognitive decline, myoclonia, a generalized periodic pattern on EEG and deep white matter abnormalities on MRI. However, imaging can be normal in early stages.

Aim: We report herein the case of a previously healthy 13-years-old girl with an unusual radiological presentation.

Results: She presented with unilateral myoclonia, cognitive decline with memory impairment and a first brain MRI with swelling of both hippocampi mimicking limbic encephalitis. Measles antibodies were positive in CSF and the EEG showed slow periodic complexes.

Conclusion: This unusual radiological presentation has never been described in SSPE. Relationship between virus and limbic system are discussed.
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http://dx.doi.org/10.1016/j.ejpn.2011.05.001DOI Listing
November 2011
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