RESUMO
Paroxysmal nonepileptic disorders are very frequent in infants and children and pediatric neurologists need to be as familiar with them as with epileptic seizures. Syncopes are the most important of these episodic disorders and amongst the syncopes the various subtypes of so-called neurally mediated syncopes (vagal, vasovagal, and so forth) predominate. In such syncopes there is almost always a trigger or provoking situation and this is the major clinical clue to the diagnosis. Whatever the mechanism of a syncope it is commonly "convulsive" in that there is a motor element, with tonic extensions and arrhythmic nonepileptic spasms ("jerks"). This everyday situation must be distinguished from the much less common combination of a syncope and a true epileptic seizure. In such anoxic-epileptic seizures the epileptic component is usually clonic, with rhythmic or semi-rhythmic jerks quite different from the arrhythmic spasms of the usual nonepileptic convulsive syncope. Syncope from compulsive Valsalva maneuver may be extremely frequent in affected (usually autistic) children. Diagnosis is easy if one obtains a video recording with audio: the premonitory hyperventilation stops leaving 11 seconds of silence before the tonic extension that signifies the syncope. Syncopes of more serious kind include those in long QT syndrome, hyperekplexia, paroxysmal extreme pain disorder, and congenital myasthenia; each has recognizable characteristics. Other nonsyncopal nonepileptic paroxysmal disorders are described further in the text.
Assuntos
Narcolepsia/diagnóstico , Convulsões/diagnóstico , Síncope/diagnóstico , Criança , Diagnóstico Diferencial , Humanos , Manobra de Valsalva , Gravação em VídeoRESUMO
Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.
Assuntos
Anormalidades Múltiplas/genética , Predisposição Genética para Doença/genética , Telangiectasia Retiniana/genética , Proteínas de Ligação a Telômeros/genética , Telômero/patologia , Sequência de Bases , Citometria de Fluxo , Histonas/metabolismo , Dados de Sequência Molecular , Telangiectasia Retiniana/patologia , Análise de Sequência de DNA/métodosAssuntos
Síndrome de Asperger/diagnóstico , Transtorno Autístico/diagnóstico , Doença de Leigh/diagnóstico , Pais , Síndrome de Asperger/fisiopatologia , Transtorno Autístico/fisiopatologia , Pré-Escolar , Movimentos Oculares , Feminino , Humanos , Lactente , Doença de Leigh/fisiopatologia , MasculinoRESUMO
We reviewed those paroxysmal disorders of infancy and of the newborn in which the normal process of bathing may be an important trigger. We focused on infant bathing in normal temperature water (37 degrees C, range 36-38 degrees C) rather than in hot water that is above body temperature. Four principal diagnostic categories emerged: bathing epilepsy, alternating hemiplegia of childhood, hyperekplexia and paroxysmal extreme pain disorder. Bathing or water immersion epilepsy was the best studied and is arguably distinct from hot water epilepsy. The paroxysmal episodes previously attributed to aquagenic urticaria may have been examples of bathing epilepsy with a genetic component. Despite suggestions in the literature to the contrary, no convincing reports of bath-induced infantile syncope have been found. The underlying mechanisms of bath-induced paroxysmal disorders in infancy remain poorly understood, but all have autonomic manifestations and some if not all may be channelopathies.
Assuntos
Banhos , Epilepsia Reflexa/etiologia , Hemiplegia/etiologia , Dor/etiologia , Síncope/etiologia , Água , Epilepsia Reflexa/fisiopatologia , Hemiplegia/fisiopatologia , Humanos , Lactente , Recém-Nascido , Dor/fisiopatologia , Síncope/fisiopatologia , TemperaturaAssuntos
Neurologia/história , Adolescente , Adulto , Manchas Café com Leite/genética , Criança , Cardiopatias/complicações , História do Século XX , Humanos , Deficiências da Aprendizagem/genética , Deficiências da Aprendizagem/psicologia , Masculino , Debilidade Muscular/etiologia , Doenças do Sistema Nervoso Periférico/etiologia , Senso de Humor e Humor como AssuntoAssuntos
Cuidadores/psicologia , Ataxia de Friedreich/diagnóstico , Simulação de Doença/diagnóstico , Neurologia/ética , Relações Médico-Paciente/ética , Acidente Vascular Cerebral/diagnóstico , Adolescente , Criança , Erros de Diagnóstico/prevenção & controle , Feminino , Ataxia de Friedreich/tratamento farmacológico , Ataxia de Friedreich/reabilitação , Humanos , Masculino , Simulação de Doença/psicologia , Neurologia/normas , Acidente Vascular Cerebral/psicologiaAssuntos
Doença de Huntington/diagnóstico , Distrofias Musculares/diagnóstico , Fenilcetonúrias/diagnóstico , Gânglios da Base/patologia , Córtex Cerebral/patologia , Criança , Pré-Escolar , Humanos , Doença de Huntington/genética , Doença de Huntington/fisiopatologia , Masculino , Distrofias Musculares/genética , Distrofias Musculares/fisiopatologia , Fenilcetonúrias/genética , Fenilcetonúrias/fisiopatologiaAssuntos
Epilepsia/diagnóstico , Epilepsia/história , Fenômenos Fisiológicos Oculares , Criança , Eletroencefalografia , História do Século XX , Humanos , Hipóxia/complicações , Hipóxia/fisiopatologia , Pressão , Reflexo/fisiologia , Mecânica Respiratória/fisiologia , Síncope/diagnóstico , Síncope/fisiopatologiaRESUMO
In 1984, Jean Aicardi and Françoise Goutières described 8 children showing both severe brain atrophy and chronic cerebrospinal fluid lymphocytosis, with basal ganglia calcification in at least one member of each affected family. The course was rapid to death or a vegetative outcome. Aicardi and Goutières correctly predicted that the disorder would be genetic, but emphasised that "some features, especially the pleocytosis, may erroneously suggest an inflammatory condition". The increased interferon-alpha in affected children (Pierre Lebon, Paris) mimicked congenital viral infection, but the associated chilblains (pernio) pointed to lupus erythematosus and an autoimmune mechanism. Genetic research led by Yanick Crow has clarified these puzzling relationships in Aicardi-Goutières syndrome, a syndrome that now includes conditions previously known as microcephaly-intracranial calcification syndrome, pseudo-TORCH and Cree encephalitis. At the time of writing, Crow's team has discovered that over 80% of families with Aicardi-Goutières syndrome have mutations in one of four nuclease genes, the exonuclease TREX1 and the genes for all three subunits of the ribonuclease H2 enzyme complex. Aicardi-Goutières syndrome is both genetically and phenotypically heterogeneous, with a range of severity from life-threatening perinatal illness to mild late infancy onset. All infants of whatever genotype have increased interferon-alpha in the first year of life and this appears to be the final common pathway that links Aicardi-Goutières syndrome, congenital virus infection and systemic lupus erythematosus.
Assuntos
Doenças Autoimunes do Sistema Nervoso/enzimologia , Doenças Autoimunes do Sistema Nervoso/genética , Doenças dos Gânglios da Base/enzimologia , Doenças dos Gânglios da Base/genética , Exodesoxirribonucleases/genética , Predisposição Genética para Doença/genética , Fosfoproteínas/genética , Doenças Autoimunes do Sistema Nervoso/fisiopatologia , Doenças dos Gânglios da Base/fisiopatologia , Calcinose/enzimologia , Calcinose/genética , Calcinose/fisiopatologia , Diagnóstico Diferencial , Humanos , Lactente , Recém-Nascido , Interferon-alfa/genética , Linfocitose/líquido cefalorraquidiano , Ribonuclease H/genética , SíndromeRESUMO
A recent article in this journal suggested that ocular compression during electroencephalography was useful in distinguishing "breath-holding spells and syncope" from epileptic seizures. The method proposed involved measurement of the RR interval on the simultaneously recorded electrocardiographic trace and determining both the absolute RR lengthening and the change in RR interval as compared with the baseline value. It is argued by the present author that this is not an appropriate way to come to a diagnosis in episodic loss of consciousness in children. It is pointed out that so-called "breath-holding spells" are reflex syncopes and that the diagnosis of reflex syncopes should be by clinical history, even if this means delaying the diagnosis until a future consultation. Published evidence on the nature and clinical diagnosis of reflex syncopes in infants and children is reviewed in depth. It is concluded that routine electroencephalography is not an appropriate investigation when the diagnosis of episodic loss of consciousness is in doubt and has the implicit danger of false positive "abnormality". Aside from scientific exploration of the developing autonomic nervous system, the only current indication for diagnostic ocular compression is to induce a syncope so that its nature may be better understood. Such a circumstance might be a history of an apparent reflex syncope but with atypical features, including prolonged post-syncopal unconsciousness such as might indicate epileptic absence status. Several additional investigations of a primarily cardiological nature may be indicated in some cases, but a wait-and-see policy is usually to be preferred.
Assuntos
Epilepsia/fisiopatologia , Olho/fisiopatologia , Síncope/diagnóstico , Síncope/fisiopatologia , Diagnóstico Diferencial , Eletrocardiografia , Eletroencefalografia , Humanos , RespiraçãoRESUMO
Aicardi-Goutières syndrome (AGS) is an autosomal recessive neurological disorder, the clinical and immunological features of which parallel those of congenital viral infection. Here we define the composition of the human ribonuclease H2 enzyme complex and show that AGS can result from mutations in the genes encoding any one of its three subunits. Our findings demonstrate a role for ribonuclease H in human neurological disease and suggest an unanticipated relationship between ribonuclease H2 and the antiviral immune response that warrants further investigation.
Assuntos
Transtornos Heredodegenerativos do Sistema Nervoso/enzimologia , Transtornos Heredodegenerativos do Sistema Nervoso/genética , Ribonuclease H/genética , Sequência de Aminoácidos , Sequência de Bases , DNA/genética , Encefalite Viral/congênito , Feminino , Humanos , Masculino , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Estrutura Quaternária de Proteína , Subunidades Proteicas , Ribonuclease H/química , Ribonuclease H/metabolismo , SíndromeRESUMO
Hyperekplexia is a human neurological disorder characterized by an excessive startle response and is typically caused by missense and nonsense mutations in the gene encoding the inhibitory glycine receptor (GlyR) alpha1 subunit (GLRA1). Genetic heterogeneity has been confirmed in rare sporadic cases, with mutations affecting other postsynaptic glycinergic proteins including the GlyR beta subunit (GLRB), gephyrin (GPHN) and RhoGEF collybistin (ARHGEF9). However, many individuals diagnosed with sporadic hyperekplexia do not carry mutations in these genes. Here we show that missense, nonsense and frameshift mutations in SLC6A5 (ref. 8), encoding the presynaptic glycine transporter 2 (GlyT2), also cause hyperekplexia. Individuals with mutations in SLC6A5 present with hypertonia, an exaggerated startle response to tactile or acoustic stimuli, and life-threatening neonatal apnea episodes. SLC6A5 mutations result in defective subcellular GlyT2 localization, decreased glycine uptake or both, with selected mutations affecting predicted glycine and Na+ binding sites.