RESUMEN
Autoantibodies directed against the N-methyl-D-aspartate receptor (NMDAR-Ab) are pathogenic immunoglobulins detected in patients suffering from NMDAR encephalitis. NMDAR-Ab alter the receptor membrane trafficking, synaptic transmission and neuronal network properties, leading to neurological and psychiatric symptoms in patients. Patients often have very little neuronal damage but rapid and massive (treatment-responsive) brain dysfunctions related to an unknown early mechanism of NMDAR-Ab. Our understanding of this early molecular cascade remains surprisingly fragmented. Here, we used a combination of single molecule-based imaging of membrane proteins to unveil the spatiotemporal action of NMDAR-Ab on live hippocampal neurons. We first demonstrate that different clones of NMDAR-Ab primarily affect extrasynaptic (and not synaptic) NMDARs. In the first minutes, NMDAR-Ab increase extrasynaptic NMDAR membrane dynamics, declustering its surface interactome. NMDAR-Ab also rapidly reshuffle all membrane proteins located in the extrasynaptic compartment. Consistent with this alteration of multiple proteins, effects of NMDAR-Ab were not mediated through the sole interaction between the NMDAR and EphB2 receptor. In the long term, NMDAR-Ab reduce the NMDAR synaptic pool by slowing down receptor membrane dynamics in a cross-linking-independent manner. Remarkably, exposing only extrasynaptic NMDARs to NMDAR-Ab was sufficient to produce their full-blown effect on synaptic receptors. Collectively, we demonstrate that NMDAR-Ab initially impair extrasynaptic proteins, then the synaptic ones. These data thus shed new and unsuspected light on the mode of action of NMDAR-Ab and, probably, our understanding of (extra)synaptopathies.
Asunto(s)
Autoanticuerpos , Hipocampo , Neuronas , Receptores de N-Metil-D-Aspartato , Receptores de N-Metil-D-Aspartato/inmunología , Receptores de N-Metil-D-Aspartato/metabolismo , Autoanticuerpos/inmunología , Autoanticuerpos/farmacología , Animales , Hipocampo/metabolismo , Neuronas/metabolismo , Ratas , Sinapsis/metabolismo , Humanos , Células Cultivadas , Receptor EphB2/metabolismo , Ratones , Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunologíaRESUMEN
AIM: To study long-term clinical and cognitive outcomes of patients with anti-N-methyl-d-aspartate receptor encephalitis (NMDAR-E), an acute autoimmune neurological disease with severe acute presentations. METHOD: In this French multicentre retrospective observational cohort study, patients no older than 18 years with a follow-up of at least 2 years were included. Data from clinical and cognitive assessments were collected. RESULTS: Eighty-one patients were included (57 females, 24 males; median age 10 years 7 months [range 1-18 years], median follow-up 40 months [range 25-53 months]). At last follow-up, 35 patients (45%) had cognitive impairment, 48 (70%) had academic difficulties, and 65 (92%) needed rehabilitation. Seventy-one patients (88%) had a modified Rankin Scale score of no more than 2. A higher number of symptoms at diagnosis was associated with cognitive impairment (p = 0.01), while an abnormal electroencephalogram at diagnosis increased the risk of academic difficulties (p = 0.03). INTERPRETATION: Although most children with NMDAR-E seemed to recover from motor disabilities, more than 45% had cognitive and academic difficulties. The initial severity of symptoms seems to have an impact on cognition and academic performances. WHAT THIS PAPER ADDS: Forty-five per cent of patients had cognitive impairment at ≥2 years diagnosis of anti-N-methyl-d-aspartate receptor encephalitis (NMDAR-E). Seventy per cent of patients had academic difficulties at ≥2 years diagnosis of NMDAR-E. Ninety-two per cent of patients needed rehabilitative care at ≥2 years diagnosis of NMDAR-E. A high number of symptoms at diagnosis were associated with cognitive impairment.
Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Disfunción Cognitiva , Masculino , Femenino , Niño , Humanos , Lactante , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Estudios Retrospectivos , Disfunción Cognitiva/complicaciones , Cognición , Receptores de N-Metil-D-AspartatoRESUMEN
Seventeen-day-old twins were hospitalized for neonatal herpes simplex virus 1 (HSV-1) with central nervous system disease and internal capsule and thalamic lesions on magnetic resonance imaging (MRI). They were treated with the usual intravenous (IV) treatment and oral therapy for 6 months. The clinical course was good in both children with negative HSV polymerase chain reaction on completion of IV therapy. The neurological condition recurred in one child with new radiological lesions at 7 months of age, 2 weeks after discontinuation of oral treatment. Cerebral lesions highlighted on the MRI scan are specific to the neonatal period and impact long-term prognosis. The likely genetic predisposition in this case is interesting and requires further investigation. In addition, this case raises questions about the duration of oral acyclovir suppressive therapy.
Asunto(s)
Aciclovir/administración & dosificación , Antivirales/administración & dosificación , Enfermedades Virales del Sistema Nervioso Central , Herpes Simple , Herpesvirus Humano 1/patogenicidad , Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Enfermedades Virales del Sistema Nervioso Central/tratamiento farmacológico , Enfermedades Virales del Sistema Nervioso Central/patología , Enfermedades Virales del Sistema Nervioso Central/fisiopatología , Enfermedades en Gemelos , Electroencefalografía , Femenino , Herpes Simple/diagnóstico , Herpes Simple/tratamiento farmacológico , Herpes Simple/patología , Herpes Simple/fisiopatología , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Masculino , RecurrenciaRESUMEN
OBJECTIVE: To describe the mode of onset of SCN8A-related severe epilepsy in order to facilitate early recognition, and eventually early treatment with sodium channel blockers. METHODS: We reviewed the phenotype of patients carrying a mutation in the SCN8A gene, among a multicentric cohort of 638 patients prospectively followed by several pediatric neurologists. We focused on the way clinicians made the diagnosis of epileptic encephalopathy, the very first symptoms, electroencephalography (EEG) findings, and seizure types. We made genotypic/phenotypic correlation based on epilepsy-associated missense variant localization over the protein. RESULTS: We found 19 patients carrying a de novo mutation of SCN8A, representing 3% of our cohort, with 9 mutations being novel. Age at onset of epilepsy was 1 day to 16 months. We found two modes of onset: 12 patients had slowly emerging onset with rare and/or subtle seizures and normal interictal EEG (group 1). The first event was either acute generalized tonic-clonic seizure (GTCS; Group 1a, n = 6) or episodes of myoclonic jerks that were often mistaken for sleep-related movements or other movement disorders (Group 1b, n = 6). Seven patients had a sudden onset of frequent tonic seizures or epileptic spasms with abnormal interictal EEG leading to rapid diagnosis of epileptic encephalopathy. Sodium channel blockers were effective or nonaggravating in most cases. SIGNIFICANCE: SCN8A is the third most prevalent early onset epileptic encephalopathy gene and is associated with two modes of onset of epilepsy.
Asunto(s)
Epilepsia/genética , Canal de Sodio Activado por Voltaje NAV1.6/genética , Edad de Inicio , Sustitución de Aminoácidos , Anticonvulsivantes/uso terapéutico , Diagnóstico Tardío , Diagnóstico Precoz , Electroencefalografía , Epilepsia/diagnóstico , Epilepsia/tratamiento farmacológico , Epilepsia/fisiopatología , Femenino , Movimiento Fetal , Humanos , Lactante , Recién Nacido , Canal de Potasio KCNQ2/genética , Masculino , Proteínas Munc18/genética , Mutación Missense , Fenotipo , Embarazo , Estudios Prospectivos , Convulsiones/genética , Convulsiones/fisiopatología , Bloqueadores de los Canales de Sodio/uso terapéuticoRESUMEN
OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is commonly observed in children with epilepsy. However, factors associated with the development of ADHD and which might help to guide its therapeutic management, remain an issue of debate. METHODS: We conducted a multicenter prospective observational study that included children, aged 6-16 years, with both epilepsy and ADHD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. After inclusion, patients entered a 12-16 week follow-up period during which they were either treated with methylphenidate or they did not receive specific ADHD treatment. ADHD was evaluated with the ADHD Rating Scale-IV. RESULTS: One hundred sixty-seven patients were included, of which 91 were seizure-free during the preinclusion baseline period. At inclusion, the ADHD Rating Scale-IV total score was 30.4 ± (standard deviation) 9.2, the inattentive subscore was 17.3 ± 4.4, and the hyperactive subscore was 13.2 ± 6.6. We did not detect any difference of ADHD Rating Scale-IV scores across patients' age or gender, age at epilepsy onset, epilepsy syndrome, seizure frequency, or number of ongoing antiepileptic drugs. Methylphenidate was initiated in 61 patients, including 55 in whom a follow-up evaluation was available. At the last follow-up, 41 patients (75%) treated with methylphenidate and 39 (42%) of those who did not received ADHD therapy demonstrated ≥25% decrease of ADHD Rating Scale-IV total score (p < 0.001). Response to methylphenidate was greater in girls but was not influenced by any epilepsy-related variables. SIGNIFICANCE: We did not detect any epilepsy-related factor associated with the severity of ADHD. Twenty-five percent of patients did not respond to methylphenidate. A better understanding of the pathologic process that underlies ADHD development in childhood epilepsy might be required to improve therapeutic strategies.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Epilepsia/complicaciones , Metilfenidato/uso terapéutico , Adolescente , Estimulantes del Sistema Nervioso Central/efectos adversos , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Metilfenidato/efectos adversos , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
Activity-dependent modulations of N-methyl-D-aspartate glutamate receptor (NMDAR) trapping at synapses regulate excitatory neurotransmission and shape cognitive functions. Although NMDAR synaptic destabilization has been associated with severe neurological and psychiatric conditions, tuning NMDAR synaptic trapping to assess its clinical relevance for the treatment of brain conditions remains a challenge. Here, we report that ketamine (KET) and other clinically relevant NMDAR open channel blockers (OCBs) promote interactions between NMDAR and PDZ-domain-containing scaffolding proteins and enhance NMDAR trapping at synapses. We further show that KET-elicited trapping enhancement compensates for depletion in synaptic receptors triggered by autoantibodies from patients with anti-NMDAR encephalitis. Preventing synaptic depletion mitigates impairments in NMDAR-mediated CaMKII signaling and alleviates anxiety- and sensorimotor-gating-related behavioral deficits provoked by autoantibodies. Altogether, these findings reveal an unexpected dimension of OCB action and stress the potential of targeting receptor anchoring in NMDAR-related synaptopathies.
RESUMEN
BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity in children with epilepsy, which management mostly relies on the usual treatments of ADHD, especially methylphenidate. Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed as an alternative therapeutic approach in ADHD without epilepsy but has never been evaluated in epilepsy-associated ADHD. METHODS: A multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA, in eicosapentaenoic- and docosahexaenoic-acid form, conjugated to a phospholipid vector (PS-Omega3) in children aged >6 and <16-years old, and suffering from any type of epilepsy and ADHD (inattentive or combined type) according to DSM-V. After a 4-week baseline period, patients were allocated (1:1) either to placebo group or to PS-Omega 3 group and entered a 12 week-double-blind treatment period which was followed by a 12 week-open-label treatment period. The primary outcome was the reduction of the ADHD-rating scale IV attention-deficit subscore after 12 weeks of treatment. RESULTS: The study was stopped early because of lack of eligible participants and the expected sample size was not reached. Seventy-four patients were randomized, 44 in PS-Omega3, and 30 in the placebo group. The reduction after 12 weeks of treatment in the inattention subscore of the ADHD-IV scale was -1.57 in the PS-Omega3 group, and -2.90 in the placebo group (p = 0.33, α = 5%). Results were similar after 24 weeks of treatment and for all other ADHD-related secondary outcomes, with no difference between placebo and PS-Omega3. CONCLUSION: Our study remaining underpowered, no formal conclusion about the effect of Ps-Omega3 could be drawn. However, our data strongly suggested that the PS-Omega 3 formulation used in the current study did not improve ADHD symptoms in children with epilepsy. PLAIN LANGUAGE SUMMARY: Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed in ADHD but has never been evaluated in patients with both epilepsy and ADHD. To address this issue, we conducted a multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA in children with epilepsy and ADHD. The study was stopped early because of lack of eligible participants, hampering formal conclusion. However, the evolution of the ADHD symptoms at 12 and 24 weeks did not differ between placebo and PUFA supplementation, strongly suggesting that PUFA did not improve ADHD symptoms in children with epilepsy.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Epilepsia , Ácidos Grasos Omega-3 , Niño , Humanos , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Fosfatidilserinas/uso terapéutico , Resultado del Tratamiento , Ácidos Grasos Omega-3/uso terapéutico , Ácidos Grasos Insaturados/uso terapéutico , Epilepsia/tratamiento farmacológico , Suplementos DietéticosAsunto(s)
Enfermedades del Recién Nacido , Vómitos , Niño , Humanos , Lactante , Recién Nacido , Vómitos/diagnóstico , Vómitos/etiologíaRESUMEN
Thrombotic microangiopathies comprise different entities, including hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), and several other conditions. TTP is characterized by hemolytic anemia, thrombocytopenia, and multiorgan failure. TTP is the result of severe von Willebrand factor multimer cleaving protease (ADAMTS13) deficiency that is either inherited or the result of acquired autoantibodies. We report a critically ill 2-year-old girl with invasive pneumococcal disease associated HUS (p-HUS) whose condition was complicated by severe ADAMTS13 deficiency, without detectable inhibitor, in a context of multiple organ failure. The patient recovered with supportive treatment, and ADAMTS13 activity normalized without plasmatherapy. Severe ADAMTS13 deficiency appears to be a manifestation of transient endothelial cell injury in the context of severe sepsis, including invasive p-HUS. The choice of appropriate therapy should not be based on this finding.
Asunto(s)
Proteínas ADAM/deficiencia , Síndrome Hemolítico-Urémico/fisiopatología , Neumonía Neumocócica/complicaciones , Proteína ADAMTS13 , Preescolar , Femenino , Síndrome Hemolítico-Urémico/metabolismo , Síndrome Hemolítico-Urémico/microbiología , HumanosRESUMEN
Erythropoietin (Epo) is an endogenous cytokine that regulates hematopoiesis and is widely used to treat anemia. In addition, it has recently increased interest in the neurosciences since the new concept of Epo as a neuroprotective agent has emerged. The potential protective effect of human recombinant Epo (r-hu-Epo) on a hypoxic-ischemic (HI) pup rat model was studied. Cerebral HI was obtained by permanent left carotid artery ligature of pups followed by a 2-h hypoxia. Three hours after carotid occlusion, brain lesions were assessed by magnetic resonance diffusion weighted imaging. Intraperitoneal administration of r-hu-Epo (30,000 U/kg dose) limited both the HI-induced brain lesion area and the decrease in apparent diffusion coefficient (ADC) in the lesion. To identify potential mechanisms underlying the effects of Epo, immunohistochemical detection of caspase-3 and water channel protein aquaporin-4 (AQP4) were performed. No early apoptosis was detected, but up-regulation of AQP4 expression was observed in HI pups that received r-hu-Epo compared with HI animals without treatment. This study demonstrates an early neuroprotective effect of Epo with regard to brain lesion area and ADC values. One possible mechanism of Epo for decreasing brain edema and cellular swelling could be a better clearance of water excess in brain tissue, a process possibly mediated by AQP4.
Asunto(s)
Acuaporina 4/metabolismo , Encéfalo , Eritropoyetina/farmacología , Hipoxia-Isquemia Encefálica , Imagen por Resonancia Magnética/métodos , Animales , Animales Recién Nacidos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Modelos Animales de Enfermedad , Eritropoyetina/genética , Humanos , Hipoxia-Isquemia Encefálica/metabolismo , Hipoxia-Isquemia Encefálica/patología , Inmunohistoquímica , Ratas , Ratas Wistar , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologíaRESUMEN
The molecular diagnosis of early-onset epileptic encephalopathy (EOEE), an expanding field in child neurology, is becoming increasingly possible thanks to the widespread availability of next-generation sequencing and whole-exome sequencing. In the past 15 years, mutations in STXBP1, KCNQ2, SCN2A, SCN8A and numerous other genes have been reported, giving a more accurate insight for these rare diseases. Among these genes, germline mutations in Phosphatidyl Inositol Glycan A (PIGA) gene were first reported in 2012. Located on Xp22.2, PIGA is involved in the synthesis of GPI (glycosylphosphatidylinositol) which acts as a membrane anchor for different proteins: enzymes, adhesion molecules, regulation of the complement way, and co-receptor in transduction signal. Children suffering from this condition exhibit developmental delay with early-onset epilepsy, severe dysmorphic signs, multi-visceral anomalies and early death in the most severe forms. Here, we report five cases of germline PIGA mutations, with two missense mutations that have not been reported to date. We provide a new insight into the electroclinical phenotype. At the onset, epileptic spasms and focal-onset seizures with upper limbs and ocular involvements were present. Epilepsy proved pharmacoresistant in 4 out of 5 cases. Interictal EEG may be normal at the onset of epilepsy, but abnormalities in electroencephalographic studies were eventually present in all cases. Different types of seizures may be present simultaneously, and epileptic phenotypes evolve with aging.
Asunto(s)
Proteínas de la Membrana/genética , Espasmos Infantiles/genética , Espasmos Infantiles/fisiopatología , Niño , Preescolar , Electroencefalografía , Mutación de Línea Germinal , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Masculino , Mutación Missense , FenotipoRESUMEN
Autoimmune encephalitis with anti-N-methyl-d-aspartate receptor autoantibodies (NMDA-R-Abs) is a recently described disease affecting adult and pediatric patients. Symptoms of the disease are now perfectly described in the adult population but the clinical presentation is less known in young children. The aim of the present study was to describe the clinical presentation and the specificities of symptoms presented by young children with NMDA-R-Abs encephalitis to improve diagnosis of this disease, and to compare these to a series of previously published female adult patients. Fifty cases of children younger than twelve years of age diagnosed with NMDA-R-Abs encephalitis between January 1, 2007 and December 31, 2016 (27 females and 23 males) were retrospectively studied. The first neurological symptoms observed in young children with NMDA-R-Abs encephalitis were characterized by seizure (72%), especially focal seizure (42%), within a median of 15 days before other encephalitis symptoms; other patients mostly had behavioral disorders (26%). The seizures were frequently difficult to diagnose because of the transient unilateral dystonic or tonic posturing presentation or sudden unilateral pain in the absence of clonic movements. A post-ictal motor deficit was also frequently observed. This clinical presentation is different from that observed in adult females with NMDA-R-Abs encephalitis who initially present mainly psychiatric disorders (67%) or cognitive impairment (19%), and less frequently seizures (14%). The diagnosis of NMDA-R-Abs encephalitis should be systematically considered in young children of both sexes who present neurological symptoms suggesting recent seizures (focal or generalized) without obvious other etiology.
Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Adolescente , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Niño , Trastornos de la Conducta Infantil/etiología , Preescolar , Femenino , Humanos , Masculino , Estudios Retrospectivos , Convulsiones/etiologíaRESUMEN
Brain dysfunction is a frequent complication of the systemic inflammatory response to bacterial infection or sepsis. In the present work, the effects of intravenous bacterial lipopolysaccharide (LPS) administration on cerebral arterial blood flow were assessed with time-of-flight (TOF)-based magnetic resonance angiography (MRA) in mice. Cerebral expression of the transcription factors nuclear factor-kappaB (NF-κB) and c-Fos and that of enzymes synthesizing vasoactive mediators, such as prostaglandins and nitric oxide, known to be increased under inflammatory conditions, were studied in the same animals. Time-resolved TOF MRA revealed no differences in blood flow in the internal carotids upstream of the circle of Willis, but indicated lower flow in its lateral parts as well as in the middle and anterior cerebral arteries after intravenous LPS injection as compared to saline administration. Although LPS did not increase c-Fos expression in ventral forebrain structures of these animals, it did induce NF-κB in meningeal blood vessels. LPS also increased cerebral expression of cyclooxygenase-2 and prostaglandin E synthase mRNAs, but de novo expression occurred in veins rather than in arteries. In conclusion, our work indicates that LPS-induced systemic inflammation does not necessarily affect filling of the circle of the Willis from the periphery, but that circulating LPS alters outflow from the circle of Willis to the middle and anterior cerebral arteries. These modifications in arterial flow were not related to increased cerebral synthesis of prostaglandins, but may instead be the consequence of the action of circulating prostaglandins and other vasoactive mediators on brain-irrigating arteries during systemic inflammation.
Asunto(s)
Arterias Cerebrales/fisiopatología , Corteza Cerebral/metabolismo , Corteza Cerebral/fisiopatología , Inflamación/fisiopatología , Lipopolisacáridos/administración & dosificación , Prostaglandinas/metabolismo , Animales , Arterias Cerebrales/microbiología , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/microbiología , Ciclooxigenasa 2 , Inflamación/metabolismo , Angiografía por Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMEN
Traumatic brain injury (TBI) is the leading cause of death and disability in children. Indeed, the acute mechanical injury often evolves to a chronic brain disorder with long-term cognitive, emotional and social dysfunction even in the case of mild TBI. Contrary to the commonly held idea that children show better recovery from injuries than adults, pediatric TBI patients actually have worse outcome than adults for the same injury severity. Acute trauma to the young brain likely interferes with the fine-tuned developmental processes and may give rise to long-lasting consequences on brain's function. This review will focus on cerebrovascular dysfunction as an important early event that may lead to long-term phenotypic changes in the brain after pediatric TBI. These, in turn may be associated with accelerated brain aging and cognitive dysfunction. Finally, since no effective treatments are currently available, understanding the unique pathophysiological mechanisms of pediatric TBI is crucial for the development of new therapeutic options.
Asunto(s)
Lesiones Traumáticas del Encéfalo/patología , Encéfalo/irrigación sanguínea , Disfunción Cognitiva/fisiopatología , Lesiones del Sistema Vascular/patología , Animales , Encéfalo/patología , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/fisiopatología , Lesiones Traumáticas del Encéfalo/terapia , Niño , Disfunción Cognitiva/etiología , Humanos , Pediatría , Factores de Tiempo , Lesiones del Sistema Vascular/fisiopatologíaRESUMEN
Dystonia is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive movements, postures, or both that are typically patterned, twisting, and sometimes tremulous. It is often initiated or worsened by voluntary action and associated with overflow muscle activation. In this article we report a case of severe oromandibular dystonia, which is a specific form of dystonia characterized by involuntary, action-induced tonic or clonic spasms of the masticatory, lingual, and pharyngeal musculature. Episodes of repeated tongue biting in a 17-month-old girl caused her to stay in the PICU for 4 weeks. These episodes were the consequence of dystonia induced by a perinatal stroke. We highlight the specific dental management that enabled us to treat the child without extractions. Facing this type of complex illness, we insist on the importance of interdisciplinary work with the goal of avoiding outdated techniques. The use of botulinum toxin seemed relevant.
Asunto(s)
Trastornos Distónicos/complicaciones , Conducta Autodestructiva/complicaciones , Lengua/lesiones , Trismo/prevención & control , Inhibidores de Captación Adrenérgica/uso terapéutico , Toxinas Botulínicas/uso terapéutico , Trastornos Distónicos/tratamiento farmacológico , Femenino , Humanos , Lactante , Protectores Bucales , Bloqueo Neuromuscular , Grupo de Atención al Paciente , Recurrencia , Conducta Autodestructiva/terapia , Tetrabenazina/uso terapéutico , Lengua/cirugía , Extracción Dental , Trismo/complicacionesRESUMEN
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.
Asunto(s)
Arteriopatías Oclusivas/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Arteriopatías Oclusivas/complicaciones , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/etiología , Enfermedades de las Arterias Carótidas/complicaciones , Angiografía Cerebral , Parálisis Cerebral/etiología , Discapacidades del Desarrollo/etiología , Epilepsias Parciales/etiología , Femenino , Humanos , Recién Nacido , Discapacidad Intelectual/etiología , Angiografía por Resonancia Magnética , Masculino , Placenta/patología , Embarazo , Factores de Riesgo , Accidente Cerebrovascular/etiologíaRESUMEN
The objective of this study is to describe the treatment and outcome of children and adolescents with N-methyl-D-aspartate receptor (NMDA-R) encephalitis. A retrospective study of children and adolescents with NMDA-R encephalitis was performed by the French Paraneoplastic Neurological Syndrome Reference Center between January 1, 2007 and December 31, 2012. The modified Rankin scale (mRS) was used to assess outcome. Thirty-six children and adolescents with NMDA-R encephalitis were studied. All of the patients received first-line immunotherapy (corticosteroids, intravenous immunoglobulins or plasma exchange), and 81% received second-line immunotherapy (rituximab or cyclophosphamide). Median time between first-line and second-line treatment was 26 days. During the first 24 months, 30 of 36 patients (83%) achieved a good outcome (mRS ≤ 2) and 20 of 36 patients (56%) achieved complete recovery (mRS = 0). Median time to good outcome and to complete recovery was 6 and 24 months, respectively. Three patients (8%) relapsed, one patient died. In multivariate analysis, age >12 years was a predictor of good outcome and initial mRS ≤ 3 was a predictor of complete recovery. Despite a higher rate of patients who received second-line immunotherapy, the outcome of the patients in the present series was very similar to the outcome reported in previous series. The present study highlights the need for clinical trials to determine the optimal treatment of NMDA-R encephalitis.
Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/terapia , Inmunoterapia/métodos , Evaluación de Resultado en la Atención de Salud , Adolescente , Factores de Edad , Encefalitis Antirreceptor N-Metil-D-Aspartato/fisiopatología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Intercambio Plasmático/métodos , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
We report a 19 year-old patient carrying a terminal 20p microdeletion. She displayed clinical features resembling those of two other previously described patients. We suggest that a specific phenotype can be associated with this chromosomal anomaly. Mental retardation, epilepsy, and dysmorphic signs including low-set ears and overfolded helices seem highly characteristic of this syndrome and may define major diagnostic criteria of a recognizable phenotype. Delayed closure of fontanella, delayed permanent teeth eruption, visual disturbances, prominent ear lobes, prominent nasal root and ridge, thin upper lip and brachydactyly may represent inconstant minor criteria.