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OBJECTIVE: Classification of electroencephalogram (EEG) background has been established to predict outcome in neonates with hypoxic ischemic encephalopathy (HIE). However, the impact of phenobarbital therapy on the predictability of EEG background has not been studied. Our objective is to determine if EEG background after treatment with phenobarbital during therapeutic hypothermia (TH) remains a good predictor for brain injury in neonates with HIE. STUDY DESIGN: This is a single-center, retrospective study of consecutive neonates with HIE who underwent TH and EEG monitoring from October 2017 to March 2021. Per institutional protocol, all infants received a dose of prophylactic phenobarbital and bumetanide therapy at the onset of TH for sedative and neuroprotective measures. The initial 3 hours of EEG background activity was classified based on national guidelines. Infants were separated into two groups based on EEG background scores: group 1 (normal-mild, n = 30) and group 2 (moderate-severe, n = 36). Brain magnetic resonance imaging (MRI) results were scored based on the National Institute of Child Health and Human Development (NICHD) criteria. Adverse outcomes were defined as death before MRI or NICHD brain injury score > 1A. RESULTS: Infants in group 2 had lower Apgar scores at 5 minutes of age, severe acidemia, moderate to severe encephalopathy score, and earlier initiation of EEG monitoring than infants in group 1. Moderate to severe EEG background score was associated with presence of brain injury on MRI or death (p = 0.003), and this association remained significant even after adjustment for independent risk factors (odds ratio = 56.24 [95% confidence interval = 1.841-1718], p = 0.021). CONCLUSION: Phenobarbital therapy does not affect the ability of EEG to predict adverse outcome in infants with perinatal asphyxia during TH. KEY POINTS: · EEG has a clinical utility for predicting outcome in neonates with hypoxia-ischemia.. · Phenobarbital therapy is commonly used in neonates, and may impact EEG background findings.. · In spite phenobarbital therapy, moderate to severe EEG background abnormalities in infants with perinatal asphyxia during TH remain an excellent predictor for poor outcome..
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Congenital anophthalmia is rare and can occur due to various etiologies, including genetic defects, teratogenic exposures, and vascular disruptions. We report a rare case of right-sided congenital anophthalmia and hemicerebral dysgenesis in association with ipsilateral hemicerebral vascular dysgenesis in a neonate. Postnatal neuroimaging was conspicuous for a "bare orbit sign." A unilateral cranial neurocristopathy was suspected to be an underlying etiopathology for such a diffuse defect.
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Anoftalmia , Anoftalmia/complicações , Anoftalmia/diagnóstico por imagem , Anoftalmia/genética , Humanos , Recém-Nascido , Neuroimagem , ÓrbitaRESUMO
Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease caused by autosomal recessive mutations in the GAN gene resulting in a loss of a ubiquitously expressed protein, gigaxonin. Gene replacement therapy is a promising strategy for treatment of the disease; however, the effectiveness and safety of gigaxonin reintroduction have not been tested in human GAN nerve cells. Here we report the derivation of induced pluripotent stem cells (iPSCs) from three GAN patients with different GAN mutations. Motor neurons differentiated from GAN iPSCs exhibit accumulation of neurofilament (NF-L) and peripherin (PRPH) protein and formation of PRPH aggregates, the key pathological phenotypes observed in patients. Introduction of gigaxonin either using a lentiviral vector or as a stable transgene resulted in normalization of NEFL and PRPH levels in GAN neurons and disappearance of PRPH aggregates. Importantly, overexpression of gigaxonin had no adverse effect on survival of GAN neurons, supporting the feasibility of gene replacement therapy. Our findings demonstrate that GAN iPSCs provide a novel model for studying human GAN neuropathologies and for the development and testing of new therapies in relevant cell types.
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Proteínas do Citoesqueleto/metabolismo , Neuropatia Axonal Gigante/genética , Células-Tronco Pluripotentes Induzidas/citologia , Proteínas de Filamentos Intermediários/genética , Neurônios Motores/metabolismo , Axônios , Diferenciação Celular , Células Cultivadas , Proteínas do Citoesqueleto/genética , Fibroblastos/citologia , Fibroblastos/metabolismo , Terapia Genética/métodos , Vetores Genéticos/genética , Neuropatia Axonal Gigante/terapia , Humanos , Filamentos Intermediários/genética , Filamentos Intermediários/metabolismo , Cariotipagem , Lentivirus/genética , Neurônios Motores/citologia , Mutação , FenótipoRESUMO
Reversed flow in the basilar artery can be acquired or congenital. Acquired reversed flow in the basilar artery can result from acute thrombosis of the basilar artery or retrograde vertebral artery flow. Congenital continuous retrograde basilar artery flow has not been described. We report a 2-day-old male presenting with hypocalcemic seizures which led us to obtain a Duplex echoencephalogram. An echocardiogram was subsequently ordered. In the coronal plane through the anterior fontanelle, retrograde flow was seen in the basilar artery and the right vertebral artery. In the axial plane through the temporal window, the flow was anteroposterior in both posterior communicating arteries. In the posterior cerebral arteries, the flow was retrograde in the P1 segment and anterograde in the P2 and P3 segments. An interrupted aortic arch was suspected. The echocardiogram showed a large perimembranous ventricular septal defect with bidirectional shunting, a hypoplastic and bicuspid aortic valve, an aortic arch interrupted between the left common carotid artery and the left subclavian artery (type B interrupted aortic arch), and a 5 mm patent ductus arteriosus with predominant right to left flow. Because of the patency of the large patent ductus arteriosus, our patient showed no sign of posterior circulation insufficiency. Prostaglandin E1 therapy was initiated immediately. Diagnosis of DiGeorge syndrome was proven. The infant underwent interrupted aortic arch repair and anterograde flow was established in the basilar artery. We conclude that congenital asymptomatic continuous retrograde flow in the basilar artery and left vertebral artery is a medical emergency as it implies the presence of type B interrupted aortic arch with large patent ductus arteriosus in a neonate.
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BACKGROUND AND PURPOSE: Brain death is defined as the irreversible cessation of brain function with a known etiology. This study aims to establish the value of duplex echoencephalography (DEG) in children fulfilling clinical brain death diagnostic criteria. METHODS: DEG must show intracranial brain structures. Power Doppler is used to assess venous flow when feasible. Color Doppler patterns in all major arteries are assessed. Spectral analysis of arterial flow is divided into four grades: grade 1: inverted flow during entire diastole with time average peak velocity (TAPV) less or equal to zero; grade 2: disappearance of the inverted diastolic flow at the end of diastole; grade 3: oscillating pattern in early diastole; and grade 4: no diastolic flow with systolic blip. To fulfill diagnosis of brain death, brain perfusion must be lost for 30 minutes. RESULTS: DEG is performed in 41 pediatric patients. In infants, loss of venous flow occurs regardless of the etiology. Grade 1 is the most common arterial color flow pattern and TAPV is always below zero. A pulsatile color flow is associated with three other types of flow patterns (grades 2-4). TAPV is not calculated, when there is loss of diastolic flow. Diagnosis of brain death is validated using nuclear brain scan in 4 patients. Two have a grade 1 flow pattern, while the other two have a grade 4 flow pattern. CONCLUSIONS: In children, DEG following a strict protocol can be used to confirm diagnosis of brain death in the appropriate clinical setting.
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Morte Encefálica , Encéfalo , Lactente , Humanos , Criança , Morte Encefálica/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Neuroimagem , Velocidade do Fluxo Sanguíneo , EcoencefalografiaRESUMO
BACKGROUND AND PURPOSE: Möbius sequence (MBS) previously known as Möbius syndrome is a rare nonprogressive developmental defect of the rhombencephalon leading to congenital abducens (VIth) and facial (VIIth) nerve palsy. Echoencephalography is the first, safe, noninvasive, and cost-effective imaging modality available at bedside. No study on the use of echoencephalography in neonates for the diagnosis of MBS has been previously reported. METHODS: In this single tertiary center study, more than 18,000 neonates underwent echoencephalographic imaging over the span of two decades. Imaging was performed through the anterior, posterior, and lambdoid fontanelles. All neonates found to have calcifications of brainstem tegmental nuclei underwent additional imaging studies. Each neonate with MBS was carefully examined by the same investigator. RESULTS: Five neonates were shown to have punctate, bilateral, symmetrical tegmental pontine calcifications through all three acoustic windows. These calcifications extended caudally in most patients, and rostrally in 2 patients. Brainstem hypoplasia was best seen through the posterior fontanelle. Three out of five infants were noted to have brainstem hypoplasia with straightening of the floor of the fourth ventricle. In two children, facial collicular bulges and hypoglossal eminences were present. All five infants fulfilled clinical diagnostic criteria of MBS. In addition, a wide array of cerebral defects is identified. Echoencephalographic findings were confirmed by other imaging modalities. CONCLUSION: Knowledge of echoencephalographic features of MBS should improve its early recognition. A detailed description of the various imaging phenotypes of MBS is necessary to characterize the etiology of this heterogeneous congenital cranial dysinnervation disorder.
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Calcinose , Transtornos Congênitos de Denervação Craniana , Síndrome de Möbius , Malformações do Sistema Nervoso , Humanos , Síndrome de Möbius/diagnóstico por imagem , Síndrome de Möbius/genética , Tronco Encefálico/diagnóstico por imagem , Calcinose/diagnóstico por imagem , EcoencefalografiaRESUMO
BACKGROUND: Menkes disease (MD) is a rare lethal X-linked, multisystem disorder of copper metabolism resulting from mutations in the ATP7A gene. Features such as Ehlers- Danlos syndrome, trichopoliodystrophy, urologic and skeletal changes have been reported. We present a case of classic MD treated with copper infusions who suffered from persistent natural killer (NK) cell dysfunction. CASE: A 2-year-old, Caucasian male child presented at 8-month-old of age with persistent hypotonia, kinky hair and developmental regression. Diagnosis of MD was based on low serum levels of copper [5 mg/dl (18-37)] and ceruloplasmin [18 ug/dl (75-153)] and gene-targeted deletion/duplication analysis performed by the reference laboratory. Brain MRI showed mild hypoplasia of the cerebellar vermis and vascular tortuosity typical of MD. Copper chloride treatment was immediately initiated. The child became more alert with excellent eye contact and purposeful movements. The child was hospitalized for recurrent respiratory infections, each time caused by enterovirus as confirmed by multiplex polymerase chain reaction (PCR). Extensive immunologic studies were negative, except for a severe NK cell dysfunction on multiple occasions (0.6 NK lytic Units; N > 2.6). CONCLUSION: We postulate that NK cell dysfunction in a classic MD can be explained by the deficient incorporation of copper in the endoplasmic reticulum resulting in an abnormal Fenton chemistry within phagosomes.
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Síndrome dos Cabelos Torcidos , Pré-Escolar , ATPases Transportadoras de Cobre/genética , Humanos , Lactente , Células Matadoras Naturais , Masculino , Síndrome dos Cabelos Torcidos/diagnóstico , Síndrome dos Cabelos Torcidos/genética , Hipotonia Muscular , MutaçãoRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Guillain-Barré syndrome is characterized by progressive motor weakness, sensory changes, dysautonomia, and areflexia. Cranial nerve palsies are frequent in Guillain-Barré syndrome. Among cranial nerve palsies in Guillain-Barré syndrome, facial nerve palsy is the most common affecting around half of the cases. Facial palsy in Guillain-Barré syndrome is usually bilateral. We describe a pediatric Guillain-Barré syndrome variant presenting with unilateral peripheral facial palsy and dysphagia. A 5-year-old boy had progressive lower extremity weakness and pain 3 days prior to onset of unilateral peripheral facial palsy. On presentation, diagnosis of Guillain-Barré syndrome was supported by areflexia and albuminocytologic dissociation. His condition deteriorated with a decline in his respiratory effort and inability to handle secretions. He was given non-invasive ventilation to prevent worsening of his acute respiratory failure. Brain and spine magnetic resonance imaging scans showed enhancement of the left bulbar nerve complex and anterior and posterior cervical nerve roots with gadolinium. Treatment with intravenous immunoglobulin led to an uneventful clinical course with partial recovery within 2 weeks. In summary, Guillain-Barré syndrome should be considered as a possible cause of unilateral peripheral facial palsy. Guillain-Barré syndrome patients with facial nerve and bulbar palsy require close monitoring as they are at risk of developing acute respiratory failure. Early intervention with intravenous immunoglobulin may benefit these patients. Magnetic resonance imaging findings may lend support to early intervention.
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OBJECTIVE: To evaluate whether rates of perinatal brain injury among extremely low birth weight infants are comparable between two treatments: single-dose indomethacin prophylaxis (SGL-IP) (0.2 mg/kg, given once) vs. standard-dose indomethacin prophylaxis (STD-IP) (0.1 mg/kg/day, 3 days). METHODS: In this retrospective study, the primary outcome was perinatal brain injury (neuro-imaging evidence of intraventricular hemorrhage or periventricular leukomalacia) or death before discharge. A non-inferior efficacy of an SGL-IP regimen compared with a STD-IP regimen was determined by calculating the adjusted difference in the risk of the primary outcome using a multivariable logistic regression model. A 10-percentage point non-inferiority margin was favored. RESULTS: Prevalence rates of primary outcome were 41.7% in the SGL-IP group (n = 403) and 42.5% in the STD-IP group (n = 509) (adjusted risk difference: -1.2, 95% CI: -7.6 to +5.2, p = 0.71). CONCLUSION: Use of a single prophylactic indomethacin dose was as effective as a standard regimen in preventing perinatal brain injury.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Hemorragia Cerebral/prevenção & controle , Indometacina/administração & dosagem , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Leucomalácia Periventricular/prevenção & controle , Alabama/epidemiologia , Hemorragia Cerebral/epidemiologia , Esquema de Medicação , Estudos de Equivalência como Asunto , Feminino , Mortalidade Hospitalar , Humanos , Recém-Nascido , Leucomalácia Periventricular/epidemiologia , Modelos Logísticos , Masculino , Análise Multivariada , Estudos RetrospectivosRESUMO
Lhermitte-Duclos disease is a rare hamartomatous tumor of the cerebellum resulting from a mutation in the phosphatase and tensin homolog (PTEN) gene: it has been reported in fewer than 10 infants. Rapamycin treatment has not yet been described in Lhermitte-Duclos disease. The infant underwent shunt placement shortly after birth for aqueductal stenosis. Her clinical progression included failure to thrive, seizures, episodes of decerebrate posturing, loss of respiratory drive, and pituitary insufficiency from mass effect. The characteristic "tiger stripe" sign on imaging prompted diagnosis. Rapamycin therapy was initiated at 18 months. Within 5 months, our patient has become responsive to her surroundings and had return of spontaneous breathing. Repeat magnetic resonance imaging (MRI) reveals lack of brainstem compression or distortion of pituitary stalk. Rapamycin should be considered in cases of Lhermitte-Duclos disease where surgical removal may not be an option, as in our case where the cerebellum was entirely involved.
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Antibióticos Antineoplásicos/uso terapêutico , Encéfalo/diagnóstico por imagem , Síndrome do Hamartoma Múltiplo/tratamento farmacológico , Sirolimo/uso terapêutico , Feminino , Síndrome do Hamartoma Múltiplo/diagnóstico por imagem , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Resultado do TratamentoRESUMO
Congenital lymphocytic choriomeningitis virus (LCMV) infection is a transient intrauterine viral infection with selective teratogenicity depending on the timing of the primary maternal infection. LCMV is cleared from the body of the fetus after the acute phase of illness and, in most cases, has lost its virulence at the time of birth. LCMV competes with extracellular matrix proteins for its tropism toward heavily glycosylated alpha-dystroglycan. In the first trimester, while tropism toward heart myoblasts is high, intrauterine infection (IUI) can lead to miscarriage or fetal demise. Later in pregnancy, LCMV becomes neurotropic with tropism toward retina and brain. Most often systemic symptoms are subtle or absent at the time of birth. The timing of the IUI determines the neuroteratogenic phenotypes of congenital LCMV infection. IUI that occurs early during gestation can lead to isolated cerebellar dysgenesis and hypoplasia. When IUI occurs during neural radial migration, echoencephalography shows defective cerebral opercularization, intracranial calcifications at the gray-white matter junction, enlarged extra-axial subarachnoid space, and cortical dysplasia. When IUI occurs after the completion of insular opercularization (late second trimester), echoencephalography shows extensive cystic periventricular leukomalacia with bi-occipital porencephaly and mild defects in gyrogenesis. A late gestation IUI induces aseptic LCMV meningitis with occlusion of the aqueduct of Sylvius, leading to congenital obstructive hydrocephalus. Congenital LCMV remains underdiagnosed as clinical manifestations are predominantly neurologic. As echoencephalography remains the preferred screening strategy for detecting neonatal central nervous system pathology, prior knowledge of echoencephalography of congenital LCMV may facilitate its recognition, prompting a serological evaluation.
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Encefalopatias , Vírus da Coriomeningite Linfocítica , Ecoencefalografia , HumanosRESUMO
BACKGROUND AND PURPOSE: By pareidolically recognizing specific patterns indicative of particular diseases, neuroimagers reinforce their mnemonic strategies and improve their neuroimaging diagnostic skills. Joubert Syndrome (JS) is an autosomal recessive disorder characterized clinically by mental retardation, episodes of abnormal deep and rapid breathing, abnormal eye movements, and ataxia. Many neuroimaging signs characteristic of JS have been reported. METHODS: In retrospective case study, two consanguineous neonates diagnosed with JS were evaluated with brain magnetic resonance imaging (MRI), computed tomography (CT), and neurosonography. RESULTS: Both cranial ultrasound and MRI of the brain showed the characteristic molar tooth sign. There was a shepherd's crook in the sagittal views of the posterior fossa where the shaft of the crook is made by the brainstem and the pons. The arc of the crook is made by the abnormal superior cerebellar peduncle and cerebellar hemisphere. By ultrasound, the shepherd's crook sign was seen through the posterior fontanelle only. CT imaging also showed the shepherd's crook sign. CONCLUSIONS: Neuroimaging diagnosis of JS, which already involves the pareidolical recognition of specific patterns indicative of the disease, can be improved by recognition of the shepherd's crook sign on MRI, CT, and cranial ultrasound.
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Encéfalo/patologia , Cerebelo/anormalidades , Neuroimagem/métodos , Retina/anormalidades , Anormalidades Múltiplas/diagnóstico , Ecoencefalografia/métodos , Anormalidades do Olho/diagnóstico , Feminino , Humanos , Recém-Nascido , Doenças Renais Císticas/diagnóstico , Imageamento por Ressonância Magnética/métodos , MasculinoAssuntos
Transtorno Autístico/diagnóstico , Suspensão da Respiração/genética , Transtornos Cromossômicos/diagnóstico , Cianose/diagnóstico , Deficiência Intelectual/diagnóstico , Transtornos do Neurodesenvolvimento/genética , Transtorno Autístico/complicações , Deleção Cromossômica , Transtornos Cromossômicos/complicações , Cromossomos Humanos Par 16 , Cianose/etiologia , Eletroencefalografia/métodos , Seguimentos , Humanos , Lactente , Deficiência Intelectual/complicações , Imageamento por Ressonância Magnética/métodos , Masculino , Transtornos do Neurodesenvolvimento/diagnóstico , Medição de RiscoRESUMO
Gliomatosis cerebri (GC) is a diffuse infiltrating glial neoplasm of astrocytic origin. GC in children is rare and difficult to diagnose, often presenting with a variety of signs and symptoms that may mimic encephalitis. We discuss here the presentation and diagnosis of GC in 2 children who were initially suspected to have acute disseminating encephalomyelitis. In this report we underscore the limitations of relying on clinical presentation and neuroimaging as well as the essential role of pathologic evaluation for the diagnosis of GC in children.
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Encefalomielite Aguda Disseminada/diagnóstico , Neoplasias Neuroepiteliomatosas/patologia , Adolescente , Criança , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Coffin-Lowry syndrome (CLS) is an X-linked mental retardation syndrome caused by defects in the RSK2 gene. We have identified a CLS family with four patients in two generations. The patients in this family, a mother and her three children (a male and two females), all have severe mental retardation with the typical CLS phenotype. In addition, brain MRI studies on the three siblings revealed abnormalities in deep subcortical white matter, thinning of the corpus callosum, hypoplastic cerebellar vermis, and asymmetry of the lateral ventricles. The degree of severity of the MRI findings correlated with the severity of mental retardation in the patients. Extensive mutation screening was performed on the entire RSK2 gene in this family. Twenty-two exons including the intron/exon junctions were amplified by PCR and subsequently sequenced on both strands. A novel mutation, a two-nucleotide insertion (298 ins TG), was identified. The insertion creates a stop codon at codon 100, resulting in a 99 amino acid truncated RSK2 protein. All patients tested have the same mutation, and no other mutation could be found in the RSK2 gene from the proband. The mutation was confirmed by PCR/RFLP. X-chromosome inactivation assay on the female patients revealed significant skewing toward inactivation of the normal RSK2 allele. Thus, this novel mutation is likely to be responsible for the unusual clinical presentation in this family, which includes full phenotypic expression in females and unique brain MRI abnormalities. The pathological function of the mutation and genotype/phenotype correlation between the mutation and this unusual clinical presentation await further clarification.
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Encéfalo/anormalidades , Encéfalo/diagnóstico por imagem , Síndrome de Coffin-Lowry/genética , Imageamento por Ressonância Magnética , Mutação , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Alelos , Éxons , Feminino , Humanos , Deficiência Intelectual/genética , Masculino , Mutagênese Insercional , Núcleo Familiar , Radiografia , Deleção de Sequência , Índice de Gravidade de Doença , Irmãos , Síndrome , Inativação do Cromossomo X/genéticaRESUMO
Many phenotypic manifestations have been reported in cardiofaciocutaneous (CFC) syndrome, but none, to date, are pathognomonic or obligatory. Previous histopathological studies reported findings in skin and hair; no autopsy studies have been published. We report the clinical and autopsy findings of a 7-year-old boy with severe CFC syndrome and malnutrition of psychosocial origin. Manifestations of CFC, reported previously, included macrocephaly and macrosomia at birth; short stature; hypotonia; global developmental delays; dry, sparse thin curly hair; sparse eyebrows and eyelashes; dilated cerebral ventricles; high cranial vault; bitemporal constriction; supraorbital ridge hypoplasia; hypertelorism; ptosis; exophthalmos; depressed nasal bridge; anteverted nostrils; low-set, posteriorly-rotated, large, thick ears; decayed, dysplastic teeth; strabismus; hyperelastic skin; wrinkled palms; keratosis pilaris atrophicans faciei; ulerythema ophryogenes; hyperkeratosis; gastroesophageal reflux; and tracheobronchomalacia. Additional findings, not previously reported, include islet cell hyperplasia, lymphoid depletion, thymic atrophy and congenital hypertrophy of peripheral nerves with onion bulb formations. Although the islet cell hyperplasia, lymphoid depletion, and thymic atrophy are nonspecific findings that may be associated with either CFC or malnutrition, the onion bulb hypertrophy is specific for a demyelinating-remyelinating neuropathy. These findings implicate congenital peripheral neuropathy in the pathogenesis of the developmental delays, feeding difficulties, respiratory difficulties, ptosis and short stature in this case. Additional studies of other cases of CFC are needed.
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Anormalidades Múltiplas/patologia , Transtornos da Nutrição Infantil/patologia , Face/anormalidades , Cardiopatias Congênitas/patologia , Doenças do Sistema Nervoso Periférico/patologia , Anormalidades da Pele , Anormalidades Múltiplas/genética , Autopsia , Criança , Evolução Fatal , Humanos , Cariotipagem , Masculino , Doenças do Sistema Nervoso Periférico/congênito , SíndromeRESUMO
BACKGROUND: Autistic Disorder is an early-onset developmental disorder with severe lifelong impact on social functioning, communication, and behavior. There is currently no marker or cure. The pathophysiology and etiology are obscure. Evidence for abnormal gamma-aminobutyric acid (GABA) function in Autistic Disorders is limited. A few case-reports and small studies have reported differences in GABA levels in plasma, platelets, and urine, compared to controls. Further studies on abnormalities of GABA function in Autistic Disorder are warranted. MATERIAL/METHODS: Plasma GABA levels were measured using a new and sensitive technique, based on gas chromatography/mass spectrometry, in a small group of youngsters with Autistic Disorder and Attention-Deficit/Hyperactivity Disorder. Participants were outpatients between ages 5-15, satisfying modern criteria for these disorders. RESULTS: Elevated plasma GABA levels were found in youngsters with Autistic Disorder. Psychotropic medications did not seem to affect plasma GABA levels in this study. Plasma GABA levels decreased with age. CONCLUSIONS: Elevated plasma GABA levels may be a biochemical marker of Autistic Disorder. This study supports the hypothesis that GABAergic mechanisms play a role in the etiology or pathophysiology of Autistic Disorder. However, the hypothesis remains unspecified owing to lack of research. Future studies on the clinical associations of seizure disorders, mood disorders, and catatonia in autistic people may provide the necessary data to formulate a coherent theory of GABA dysfunction in Autistic Disorder. More trials of medication with known or suspected effects on GABA function are warranted.