RESUMO
Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P<5 × 10(-8)); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (P=1.85 × 10(-6)). A secondary analysis including an additional 211 cases and 285 controls from two closely related Latin American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (P=3.6 × 10(-7) for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder.
Assuntos
Colágenos Fibrilares/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único/genética , Síndrome de Tourette/genética , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 9/genética , Feminino , Genótipo , Humanos , Cooperação Internacional , Masculino , Metanálise como Assunto , Transtorno Obsessivo-Compulsivo/etiologia , Transtorno Obsessivo-Compulsivo/genética , Síndrome de Tourette/complicações , População Branca/genética , Adulto JovemRESUMO
OBJECTIVE: To test the hypothesis that atomoxetine does not significantly worsen tic severity relative to placebo in children and adolescents with attention deficit/hyperactivity disorder (ADHD) and comorbid tic disorders. METHODS: Study subjects were 7 to 17 years old, met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for ADHD, and had concurrent Tourette syndrome or chronic motor tic disorder. Patients were randomly assigned to double-blind treatment with placebo (n = 72) or atomoxetine (0.5 to 1.5 mg/kg/day, n = 76) for up to 18 weeks. RESULTS: Atomoxetine treatment was associated with greater reduction of tic severity at endpoint relative to placebo, approaching significance on the Yale Global Tic Severity Scale total score (-5.5 +/- 6.9 vs -3.0 +/- 8.7, p = 0.063) and Tic Symptom Self-Report total score (-4.7 +/- 6.5 vs -2.9 +/- 5.2, p = 0.095) and achieving significance on the Clinical Global Impressions (CGI) tic/neurologic severity scale score (-0.7 +/- 1.2 vs -0.1 +/- 1.0, p = 0.002). Atomoxetine patients also showed greater improvement on the ADHD Rating Scale total score (-10.9 +/- 10.9 vs -4.9 +/- 10.3, p < 0.001) and CGI severity of ADHD/psychiatric symptoms scale score (-0.8 +/- 1.1 vs -0.3 +/- 1.0, p = 0.015). Discontinuation rates were not significantly different between treatment groups. Atomoxetine patients had greater increases in heart rate and decreases of body weight, and rates of treatment-emergent decreased appetite and nausea were higher. No other clinically relevant treatment differences were seen in any other vital sign, adverse event, or electrocardiographic or laboratory measures. CONCLUSIONS: Atomoxetine did not exacerbate tic symptoms. Rather, there was some evidence of reduction in tic severity with a significant reduction of attention deficit/hyperactivity disorder symptoms. Atomoxetine treatment appeared safe and well tolerated.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Propilaminas/administração & dosagem , Transtornos de Tique/tratamento farmacológico , Adolescente , Agonistas Adrenérgicos/administração & dosagem , Agonistas Adrenérgicos/efeitos adversos , Cloridrato de Atomoxetina , Peso Corporal/efeitos dos fármacos , Criança , Comorbidade , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Efeito Placebo , Propilaminas/efeitos adversos , Taquicardia/induzido quimicamente , Resultado do TratamentoRESUMO
BACKGROUND: Self injurious behaviour (SIB), the deliberate, repetitive infliction of self harm, is present in a wide variety of neuropsychiatric disorders, including Tourette syndrome (TS). Although SIB occurs in up to 60% of individuals with TS, and can cause significant clinical impairment and distress, little is known about its aetiology. OBJECTIVE: This study examined the relationship between SIB and other behavioural features that commonly co-occur with TS in nearly 300 subjects with TS participating in three genetic studies. SIB, obsessions, compulsions, tic severity, attention deficit hyperactivity disorder related impulsivity, risk taking behaviours, and rages were systematically assessed in all subjects. METHODS: Using logistic regression, a best fit model was determined for both mild to moderate SIB and severe SIB. RESULTS: Mild/moderate SIB in TS was correlated with the presence of obsessive and compulsive symptoms such as the presence of aggressive obsessions or violent or aggressive compulsions, and with the presence of obsessive-compulsive disorder and overall number of obsessions. Severe SIB in TS was correlated with variables related to affect or impulse dysregulation; in particular, with the presence of episodic rages and risk taking behaviours. Both mild/moderate and severe SIB were also correlated with tic severity. CONCLUSIONS: This study suggests that mild/moderate and severe SIB in TS may represent different phenomena, which has implications for clinical management of these symptoms.
Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta/psicologia , Comportamento Autodestrutivo/etiologia , Comportamento Autodestrutivo/psicologia , Síndrome de Tourette/complicações , Síndrome de Tourette/psicologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/psicologia , Fúria , Assunção de Riscos , Índice de Gravidade de DoençaRESUMO
This study reports on the seizure and psychosocial outcome of 29 patients with electroclinically well-defined childhood-onset symptomatogenic or cryptogenic partial epilepsy with complex partial seizures who were followed prospectively over 14 years. Many were refractory at the time of enrollment. At 14-year follow-up, we acquired information on seizure type and frequency, psychiatric history, substance abuse, criminal activity, in addition to educational, vocational, and marital status through chart reviews and/or structured telephone interviews. Sixteen patients were only treated medically. They were divided by their following responses to medications: eight patients with less than one seizure per month were in the medically responsive group and eight patients with at least one seizure per month constituted the medically refractory group. Thirteen patients underwent focal resection for medically refractory epilepsy. Medically refractory patients displayed worse educational, vocational, social, and behavioral outcomes than medically responsive patients. Behavioral abnormalities persisted or evolved in five medically refractory patients when they became seizure free. Other studies have indicated that patients with medically refractory complex partial seizures have poor psychosocial outcomes. Although behavioral problems can occur even when seizures are well controlled, their early detection and treatment may be essential to the improvement of psychosocial outcomes.
Assuntos
Epilepsia Parcial Complexa/psicologia , Epilepsia Parcial Complexa/terapia , Ajustamento Social , Adulto , Criança , Escolaridade , Eletroencefalografia , Emprego , Epilepsia Parcial Complexa/tratamento farmacológico , Epilepsia Parcial Complexa/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Estado Civil , Transtornos Mentais/etiologia , Estudos Prospectivos , Psicopatologia , Resultado do TratamentoRESUMO
Tay-Sachs disease (TSD) results from a deficiency of beta-hexosaminidase A (EC 3.2.1.52) activity. A child with late-infantile TSD was found to have two HEXA mutations, 986 + 3A-->G (A-->G at the +3 position of intron 8) and 533G-->A, associated with the variant B1 form of TSD. We were able to detect exon 8-deleted, but no correctly spliced HEXA mRNA, from the non-533G-->A allele in this patient. This suggests that 986 + 3A-->G results in missplicing and, together with 533G-->A, TSD.
Assuntos
Mutação Puntual , Doença de Tay-Sachs/genética , beta-N-Acetil-Hexosaminidases/genética , Alelos , Sequência de Bases , Criança , Primers do DNA/genética , Éxons , Feminino , Heterozigoto , Hexosaminidase A , Humanos , Íntrons , Dados de Sequência Molecular , Splicing de RNA/genética , RNA Mensageiro/genéticaAssuntos
Comitês de Ética Clínica , Comissão de Ética/organização & administração , Consultoria Ética , Auditoria Administrativa , Encaminhamento e Consulta/normas , Comportamento do Consumidor , Eticistas , Comissão de Ética/normas , Retroalimentação , Processos Grupais , Relações Hospital-Paciente , Hospitais de Prática de Grupo/organização & administração , Hospitais de Prática de Grupo/normas , Ohio , Registros , Inquéritos e QuestionáriosAssuntos
Atitude do Pessoal de Saúde , Eticistas , Comitês de Ética Clínica , Comissão de Ética/estatística & dados numéricos , Hospitais de Prática de Grupo/normas , Serviços de Informação/estatística & dados numéricos , Temas Bioéticos , Ética Clínica , Conhecimentos, Atitudes e Prática em Saúde , Hospitais de Prática de Grupo/estatística & dados numéricos , Humanos , Capacitação em Serviço , Ohio , Política Organizacional , Avaliação de Programas e Projetos de Saúde/métodos , Avaliação de Programas e Projetos de Saúde/estatística & dados numéricos , Registros , Encaminhamento e Consulta/estatística & dados numéricos , Inquéritos e QuestionáriosRESUMO
Children with learning disabilities form a large pool of patients seen by neurologists for help in understanding the disability and deciding which forms of remediation are appropriate. Learning disabilities may accompany a large variety of other neurologic disabilities, but the usual child with such a problem is in excellent health. A thorough office evaluation for possible medical problems is always necessary, but most children do not require laboratory testing. All children with learning disabilities, whether or not they have accompanying neurologic problems, should be seen for psychological and/or educational evaluation. Some children may also benefit from an evaluation by a speech and language pathologist, occupational therapist, or ophthalmologist. The neurologist, alone or in association with a child psychologist, should also investigate the possible association of learning disabilities with attention deficit hyperactivity disorder. It is only for children with this component of learning problems that the possibility of medication arises. Working closely with the family, the child's school system, and other involved professionals becomes an important aspect of providing full and necessary help to children with learning disabilities. A caring physician can be a major help to the child and his family in understanding this disorder and supporting them during a difficult time.
Assuntos
Deficiências da Aprendizagem/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiologia , Mapeamento Encefálico , Criança , Eletroencefalografia , Potenciais Evocados Auditivos/fisiologia , Potenciais Evocados Visuais/fisiologia , Humanos , Deficiências da Aprendizagem/diagnóstico , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios XRESUMO
Psychogenic seizures in 21 nonepileptic children and adolescents, aged 8 to 18 (mean 14.5) years, were recorded by means of video recording and electroencephalography. The episodes included thrashing movements, limb jerking, or staring, with unresponsiveness. Ictal and interictal electroencephalograms showed no abnormalities after antiepileptic medication was discontinued. Fifteen patients had psychogenic seizures spontaneously during recording, and six had seizures in response to suggestion and intravenous saline injection. After the video-electroencephalographic evaluation, patients and families were told that the episodes were emotional in origin. All patients but 1 agreed to remain without antiepileptic medication, and 16 patients (76%) agreed to begin psychiatric treatment. At 6 to 66 (mean 30) months' follow-up, 14 of 18 (78%) were free of episodes. These data indicate that the majority of young patients with psychogenic seizures have a good outcome. A firm diagnosis is critical so that the episodes can be classified and emphasized as medically not worrisome, permitting a shift away from antiepileptic medication and toward psychiatric treatment.
Assuntos
Eletroencefalografia , Convulsões/diagnóstico , Adolescente , Criança , Seguimentos , Humanos , Prognóstico , Desempenho Psicomotor/fisiologia , Convulsões/fisiopatologia , Convulsões/psicologia , Gravação em VídeoAssuntos
Transtornos de Tique/tratamento farmacológico , Adolescente , Adulto , Criança , Clonazepam/efeitos adversos , Clonazepam/uso terapêutico , Clonidina/efeitos adversos , Clonidina/uso terapêutico , Haloperidol/efeitos adversos , Haloperidol/uso terapêutico , Humanos , Pimozida/efeitos adversos , Pimozida/uso terapêutico , Síndrome de Tourette/tratamento farmacológicoRESUMO
To evaluate the utility and safety of chronic extraoperative subdural EEG and functional localization studies in children compared to adults, we studied 61 patients each of whom had similar evaluations for epilepsy surgery, regardless of age. The 23 children and adolescents (3 to 18 years old) and the 38 adults (20 to 41 years old) each had several days and nights of extraoperative EEG from scalp and chronically-implanted subdural electrodes, and the same percentage of children and adults also had functional localization studies including cortical electrical stimulation. The methods and results of these studies and of the subsequent resections did not differ between the two groups, and they both had similar rate of complications and similar incidence of good outcome. The subdural technique was as effective and well-tolerated in children and adolescents as in adults. Other invasive EEG techniques have not yet been systematically compared between children and adults, but the subdural technique, at least, appears to be suitable for patients over a wide age range.
Assuntos
Eletrodos , Epilepsia/cirurgia , Monitorização Fisiológica/métodos , Lobo Temporal/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Eletroencefalografia , Epilepsia/complicações , Epilepsia/fisiopatologia , Seguimentos , Humanos , Lobo Temporal/fisiopatologiaRESUMO
Few detailed studies have examined the long-term outcome of complex partial seizures (CPS) in children and adolescents. Previous studies have selected patients on clinical criteria only or have included those with benign focal epileptiform discharges of childhood, nonepileptiform sharp transients, and generalized epileptiform discharges. We have followed up 29 patients with clinically and electroencephalographically defined CPS of childhood onset for five years or more. Twelve patients are seizure free, eight of them after having epilepsy surgery. Of the remaining, eight patients have intractable seizures. Only one patient was able to discontinue anticonvulsant therapy after epilepsy surgery. No patient had spontaneous remission of seizures without anticonvulsant medications. School difficulties, behavior problems, and unemployment were seen in half the group. We believe CPS in this age group are difficult to control and need aggressive management. In selected patients, epilepsy surgery offers a good chance of seizure control and improvement of educational, social, and vocational potential.