RESUMEN
Using a Sendai Virus based vector delivering Yamanaka Factors, we generated induced Pluripotent Stem Cells (iPSCs) from peripheral blood mononuclear cells of a patient affected by Ataxia Telangiectasia (AT), caused by a novel homozygous deletion in ATM, spanning exons 5-7. Three clones were fully characterized for pluripotency and capability to differentiate. These clones preserved the causative mutation of parental cells and genomic stability over time (>100 passages). Furthermore, in AT derived iPSCs we confirmed the impaired DNA damage response after ionizing radiation. All these data underline potential usefulness of our clones as in vitro AT disease model.
Asunto(s)
Proteínas de la Ataxia Telangiectasia Mutada/genética , Ataxia Telangiectasia/genética , Ataxia Telangiectasia/patología , Diferenciación Celular , Células Madre Pluripotentes Inducidas/patología , Leucocitos Mononucleares/patología , Mutación , Adulto , Células Cultivadas , Reprogramación Celular , Femenino , Homocigoto , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Leucocitos Mononucleares/metabolismo , Adulto JovenRESUMEN
The long-term course of migraine with aura (MA) has been poorly explored. The present 11-year follow-up study assessed the long-term natural history and possible prognostic factors of MA with onset in childhood or adolescence. Patients were recruited from the original case records of our department, which are specifically designed to report all headache characteristics, aura symptoms and electroencephalogram (EEG) findings. A total of 77 patients (47 females; 30 males) whose records contained detailed descriptions of both headache and aura symptoms apparently meeting the International Classification of Headache Disorders (ICHD)-II criteria for MA (i.e., 1.2.1, 1.2.2, 1.2.6) underwent structured face-to-face follow-up headache interviews, all of which were conducted by the same neurologist, who has particular expertise in this field. A multivariate model (logistic regression analysis) was used to investigate the association between possible prognostic factors and the remission of both aura and headache at follow-up. The results of our study showed that 23.4% of the MA patients were headache-free at follow-up, 44.1% still had MA and 32.5% had a transformed headache diagnosis (i.e., fulfilling the criteria for ICHD-II 1.1. or 2). Patients with basilar-type migraine (1.2.6) showed the highest headache remission rate (38.5%). Our study seems to show that migraine with typical aura (1.2.1-1.2.2) is associated with a favourable evolution of aura symptoms over time (remission of aura in 54.1% of patients). Subjects experiencing only visual aura had a lower remission rate compared with those with visual +/- sensory +/- aphasic aura symptoms (36.8% vs. 61.5%, p = 0.054). A short headache duration (<12 hrs) and the presence of EEG abnormalities at baseline were the only significant predictors of aura remission at follow-up (odds ratio [OR] = 9.12, 95% confidence interval [CI]: 1.79 +/- 46.51, and OR = 4.76, 95% CI: 1.18 +/- 19.15, respectively). No significant predictors of headache remission were found. In conclusion, our results suggest that MA shows a favourable course. Further prospective studies with detailed EEG analysis both at baseline and at follow-up are needed in order to confirm the possible prognostic role of EEG abnormalities in MA. That said, it would, in our opinion, be highly premature at present to submit children with MA to EEG examinations for prognostication purposes.
Asunto(s)
Migraña con Aura/fisiopatología , Adolescente , Edad de Inicio , Niño , Preescolar , Femenino , Humanos , Masculino , PronósticoAsunto(s)
Encefalopatías/líquido cefalorraquídeo , Encefalopatías/diagnóstico , Líquido Cefalorraquídeo/química , Perfilación de la Expresión Génica , Análisis de Secuencia por Matrices de Oligonucleótidos , Algoritmos , Encefalopatías/genética , Calcinosis/líquido cefalorraquídeo , Calcinosis/diagnóstico , Calcinosis/etiología , Líquido Cefalorraquídeo/citología , Niño , Preescolar , Análisis por Conglomerados , Estudios de Factibilidad , Femenino , Humanos , Lactante , Interferón-alfa/líquido cefalorraquídeo , Linfocitos/química , Masculino , Valor Predictivo de las Pruebas , Análisis de Componente Principal , SíndromeRESUMEN
BACKGROUND: The level of language development reached in pre-school age is considered the most reliable predictor of reading acquisition. In normally developing children, learning to read is strongly related to early language skills, and in particular to phonological processing abilities. In dyslexic children, reading abilities seem to show a correlation with phonological awareness. METHODS: A group of 65 children (aged 5-6 years) were recruited and submitted to an in-depth neuropsychological assessment [i.e. metaphonological skills, intelligence, verbal short-term memory (VSTM) and other aspects of receptive and expressive language]. We were able to identify 14 children with significant metaphonological difficulties (MD): 11 children with exclusively MD, and the other three children with specific language impairment. This study compares the neuropsychological profile obtained from children with MD with that of a peer group without any language impairment (N). RESULTS: The performances of the MD were within the normal ability range in almost all the administered tests but significantly lower compared with those of their peers without language impairment (N) in some items of the intelligence scale (Wechsler Preschool and Primary Scale of Intelligence) and in the tests of VSTM and of receptive/expressive language. Nevertheless, there were not statistically significant differences between MD and N in output phonology. CONCLUSIONS: In pre-school age, in a group of non-clinical children, with a range of abilities, those with MD appear to be at the lower end of the normal range in many other verbal skills. These children could be considered at-risk for possible subsequent difficulties learning to read and thus need to be identified and to warrant prompt treatment.
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Pruebas de Articulación del Habla/métodos , Trastornos del Habla/terapia , Niño , Preescolar , Intervención Educativa Precoz , Femenino , Humanos , Pruebas de Inteligencia/estadística & datos numéricos , Pruebas del Lenguaje , Masculino , Lectura , Pruebas de Articulación del Habla/psicología , Trastornos del Habla/complicaciones , Logopedia/métodos , Logopedia/psicologíaRESUMEN
To date, studies addressing the role of pharmacotherapy in the treatment of anorexia nervosa are limited, especially in childhood and adolescence. The aim of this retrospective naturalistic study was to evaluate the efficacy and safety of pharmacotherapy in 19 anorexic preadolescents and adolescents referred, for the first time, to a specialist psychiatry unit. Almost all the patients showed an improvement both in their eating behaviors, and in their mood and obsessive symptoms. No evidence was found of dangerous adverse events. Combined with a multidisciplinary approach that includes nutritional rehabilitation and psychotherapy, adjunctive pharmacotherapy may be useful in addressing both eating disorder psychopathology and comorbid psychiatric disorders.
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Anorexia Nerviosa/tratamiento farmacológico , Antidepresivos/uso terapéutico , Antipsicóticos/uso terapéutico , Adolescente , Antidepresivos/efectos adversos , Antipsicóticos/efectos adversos , Niño , Femenino , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
There is much evidence in the literature suggesting that children with congenital blindness can also present autistic like features. The aetiopathogenetic and clinical significance of this association is still unclear. Given the central role played by vision in development, we set out to establish the significance of autistic-like behaviours in children with early-onset severe visual impairment. Our sample comprised 24 children (13 males, 11 females; mean age 5y 2mo; range 2-11y) affected by Leber's congenital amaurosis (LCA). The results of our administration of a modified Childhood Autism Rating Scale--excluding item VII (Visual Responsiveness)--showed that only four of the children gave an overall score indicating the presence of autism (moreover, of mild/moderate degree). Hardly any of the children in our LCA sample presented major dysfunctions in their relationships with other people or in their social and emotional responsiveness, thus allowing us to exclude a genuine comorbidity with a picture of autism. Indeed, the risk facing the visually impaired child seems to concern their early interactive experiences, which may be affected by their inability to connect with others, and may be prevented through the development of specific strategies of intervention.
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Trastorno Autístico/complicaciones , Neuropatía Hereditaria Motora y Sensorial/complicaciones , Atrofias Ópticas Hereditarias/complicaciones , Visión Ocular/fisiología , Niño , Preescolar , Femenino , Humanos , Masculino , Índice de Severidad de la Enfermedad , Conducta Estereotipada/fisiologíaAsunto(s)
Antígenos CD40/deficiencia , Trasplante de Células Madre Hematopoyéticas , Inmunodeficiencia Combinada Grave/terapia , Preescolar , Supervivencia de Injerto/genética , Supervivencia de Injerto/inmunología , Humanos , Masculino , Inducción de Remisión , Inmunodeficiencia Combinada Grave/genética , Inmunodeficiencia Combinada Grave/inmunología , Trasplante HomólogoRESUMEN
BACKGROUND: Headache is a disease that has a high social impact in the paediatric as well as in the adult population, often resulting in a significant reduction in the young patient's quality of life, reflected primarily in a greater number of days off school and increasingly frequent recourse to symptomatic drugs. The idea for this study came from the clinical impression that some paediatric headache patients might benefit more from inpatient than outpatient care. AIM: The aim of our study was to compare the effectiveness of hospitalization to outpatient care of patients with newly diagnosed frequent and disabling headache. METHODS: A pragmatic randomized open-label trial was conducted at the Child Neurology Clinic of the University of Pavia, Italy. Children and adolescents with a 2- to 6-month moderate-to-severe migraine or tension-type headache history were randomized to hospital admission or outpatient assessment and followed for 6 months. The efficacy of the two therapeutic strategies was measured by counting the number of responders in each arm. Other end points included the mean frequency and duration of attacks, the number of drug prescriptions taken to control pain, and the number of patients and physicians expressing satisfaction with treatment. RESULTS: The study population included 27 girls and 23 boys aged 8 through 18 years with migraine (23 cases) or tension-type headache (27 cases). Compared to outpatient assessment, hospital admission was correlated to a significant increase in the number of responders: 0 vs. 44% (1 month), 0 vs. 68% (3 months), and 12 vs. 68% (6 months). The mean frequency and duration of attacks were significantly lower in hospitalized patients (p < 0.0001). Hospitalization was correlated with a significant reduction of patients with severe headache (p < 0.005), a reduction of drug use, and a higher number of satisfied patients and physicians (p < 0.05). Logistic regression analysis confirmed the higher responder rate among hospitalized patients after adjusting for age, sex, diagnosis, and headache characteristics or admission. CONCLUSIONS: We think hospitalization reduces the emotional mechanisms that provoke stress in children and often induce or favour headache attacks. If these mechanisms can be interrupted, the management of disease may become easier and with enduring benefits.
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Atención Ambulatoria , Hospitalización , Cefalea de Tipo Tensional/rehabilitación , Adolescente , Atención Ambulatoria/estadística & datos numéricos , Encéfalo/anatomía & histología , Encéfalo/diagnóstico por imagen , Niño , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Admisión del Paciente/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Cefalea de Tipo Tensional/diagnóstico , Cefalea de Tipo Tensional/epidemiología , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Described are the outcomes of 11 Italian patients with Aicardi-Goutières syndrome. Neurologic symptoms progressed in the first year of life and stabilized by the end of the second year in 10 patients. White matter abnormalities remained stable; cerebral atrophy was stable in four patients and progressive in two. Calcifications increased (in number and size) in two of six patients. Serial CSF and serum interferon-alpha measurements (three patients) showed reduced CSF interferon-alpha levels.
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Anomalías Múltiples/fisiopatología , Atrofia/fisiopatología , Encéfalo/fisiopatología , Calcinosis/fisiopatología , Epilepsia/fisiopatología , Trastornos Heredodegenerativos del Sistema Nervioso/fisiopatología , Anomalías Múltiples/sangre , Anomalías Múltiples/líquido cefalorraquídeo , Atrofia/congénito , Atrofia/patología , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Calcinosis/congénito , Calcinosis/patología , Líquido Cefalorraquídeo/química , Líquido Cefalorraquídeo/citología , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Genes Recesivos , Trastornos Heredodegenerativos del Sistema Nervioso/sangre , Trastornos Heredodegenerativos del Sistema Nervioso/líquido cefalorraquídeo , Humanos , Lactante , Recién Nacido , Interferón-alfa/sangre , Interferón-alfa/líquido cefalorraquídeo , Italia , Estudios Longitudinales , Masculino , Fibras Nerviosas Mielínicas/patología , Radiografía , Enfermedades Raras , Enfermedades de la Piel/fisiopatología , SíndromeRESUMEN
AIM: Personal experience in a sample group of children with AIDS vertically transmitted followed from birth to adolescence (out of 56 cases with documented HIV infection, 9 who have reached the age of 13 have been studied) is presented. METHODS: The evaluation protocol includes: hematochemical, serological and virological tests to monitor the infectious status, as well as annual EEG, CT/MRI scan to detect anatomical alteration of CNS, neurological examination, intelligence test (WISC-R), interview and projective test (Blacky Pictures) to investigate emotional situation. RESULTS: As to the status of the disease, according to the CDC classification, 2 patients are asymptomatic, 2 paucisymptomatic, 2 with moderate symptoms, 2 severely symptomatic; 1 patient died due to progressive encephalopathy. Of the 2 severely symptomatic cases, 1 presents cortical atrophy and the other basal nuclei calcifications. No one of them has clinical signs of encephalopathy. All patients receive anti-retroviral medications. From tests and interviews emotional problem-emerge, future is seen as menacing and insidious, and defensive mechanisms are fragile and inconstant; denial can lead to a refusal of the pharmacological therapy; families themselves often refuse medical staff the consent to communicate the diagnosis fearing that this could induce unbearable anguish. CONCLUSIONS: It seems important that patients are informed, considering their capacity to make front to the communication, even if one must bear in mind that understanding and accepting the diagnosis may be a long and painful process requiring a long time.
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Seropositividad para VIH , Transmisión Vertical de Enfermedad Infecciosa , Adolescente , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Niño , Preescolar , Electroencefalografía , Seropositividad para VIH/epidemiología , Seropositividad para VIH/fisiopatología , Seropositividad para VIH/psicología , Seropositividad para VIH/transmisión , Humanos , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos XRESUMEN
The authors report a girl with autosomal recessive congenital muscular dystrophy linked to chromosome 6 (MDC1A) who carries a homozygous out-of-frame deletion in exon 56 of the LAMA2 gene but has a mild phenotype. She is still ambulant at age 13 years, shows white matter abnormalities on MRI, and traces of laminin alpha2 in her muscle biopsy with one of three antibodies used. This patient suggests that modulating factors can be associated with a less severe clinical phenotype in MDC1A.
Asunto(s)
Laminina/deficiencia , Distrofias Musculares/genética , Eliminación de Secuencia , Adolescente , Biopsia , Encéfalo/patología , Niño , Cromosomas Humanos Par 6/genética , Exones/genética , Femenino , Genes Recesivos , Homocigoto , Humanos , Discapacidad Intelectual/genética , Laminina/análisis , Laminina/genética , Laminina/fisiología , Imagen por Resonancia Magnética , Músculo Esquelético/química , Músculo Esquelético/patología , Distrofias Musculares/congénito , Análisis de Secuencia de ADNAsunto(s)
Anomalías Múltiples/genética , Proteínas Portadoras/genética , Proteínas del Citoesqueleto/genética , Atresia Esofágica/patología , Proteínas del Tejido Nervioso/genética , Fístula Traqueoesofágica/patología , Translocación Genética , Anomalías Múltiples/patología , Animales , Secuencia de Bases , Encéfalo/metabolismo , Línea Celular , Preescolar , Bandeo Cromosómico , Cromosomas Humanos Par 15/genética , Cromosomas Humanos Par 6/genética , Trastornos del Conocimiento/patología , Cricetinae , Discapacidades del Desarrollo/patología , Distonina , Femenino , Perfilación de la Expresión Génica , Genotipo , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Músculos/metabolismo , Mutación , Polimorfismo de Nucleótido Simple , Isoformas de Proteínas/genéticaRESUMEN
BACKGROUND: The prevalence of tic disorders in children varies from 1% to 29% depending on the characteristics of the study population, the diagnostic criteria, and the study design and methods. AIMS: To calculate the prevalence of tic disorders among primary school children in Italy. METHODS: The study population comprised 2347 primary school children from the city of Pavia (pop. 80 073), Northern Italy. Using trained school teachers as the source of cases, all children with motor or vocal tics occurring intermittently and unpredictably out of a background of normal motor activity were accepted. The type, frequency, and circumstances of tic disorders were noted. School performance was correlated to the presence of tics. RESULTS: A total of 68 children (56 boys, 12 girls) aged 6-11 years were identified with tic disorders. The period prevalence was 2.9% (95% CI 2.3 to 3.7). The prevalence was 4.4% in boys and 1.1% in girls, with no detectable trends at age 6-11. Motor tics were present in 46 cases, vocal tics in 6, and motor and vocal tics in 16. Situation related tics were noted in 37 cases. A significant correlation was found between the presence of tic disorders and impaired school performance. DISCUSSIONS: Tic disorders are a fairly uncommon but disabling clinical disorder among primary school children from an urban community. The fairly low prevalence of this clinical condition, as compared to other reports, can be explained by the choice of stringent diagnostic criteria and the exclusion of patients with other movement disorders.
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Trastornos de Tic/epidemiología , Distribución de Chi-Cuadrado , Niño , Femenino , Humanos , Italia/epidemiología , Masculino , Prevalencia , Salud UrbanaRESUMEN
The objective of the study was to assess whether a family history of vascular disorders is more common in children and adolescents with migraine than in the general population. Family history of stroke, arterial hypertension, myocardial infarction and diabetes was investigated by history taking in relatives of ambulatory children and young adults with migraine and in a control group. The odds ratios (ORs) with 95% confidence intervals (95% CI) were used as a risk measure. Using univariate and multivariate (logistic regression) analysis, family history was assessed in the whole sample and in subgroups by sex and age, degree of relationship (parents and grandparents vs. relatives), disease type (migraine with and without aura), and type of vascular disorder. The sample included 143 cases (migraine with aura 35, migraine without aura 108) and 164 controls aged 3-24 years (mean 12 +/- 3.8 years). Patients with migraine were at increased risk of vascular disorders in parents and grandparents but not in all relatives. Multivariate analysis indicated family history of stroke as most common only in boys. In conclusion, our study provides some clues to the assumption that migraine and vascular disorders have common pathogenic mechanisms and that genetic susceptibility plays a role in increasing the risk of migraine in the offspring of families with one or more cerebrovascular or cardiovascular conditions.
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Predisposición Genética a la Enfermedad , Trastornos Migrañosos/genética , Enfermedades Vasculares/epidemiología , Enfermedades Vasculares/genética , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Niño , Preescolar , Familia , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de RiesgoRESUMEN
"Generalized epilepsy with febrile seizures plus" (GEFS+) syndrome has been recently described. This term defines a heterogeneous group of generalized epilepsies observed in several members of large pedigree studies. The syndrome spectrum has been widened by including others forms of generalized epilepsy. We report two Italian families in which the fathers showed febrile seizure plus (FS+), and two sons had severe myoclonic epilepsy of infancy (SMEI). The clinical setting of each epileptic member of the family will be discussed, focusing on the relationship with the GEFS+ group, confirming its wide clinical spectrum. In fact, GEFS+ is different from most other epilepsy syndromes as it is defined not by a set of associated symptoms but by the genetic transmission of a predisposition to febrile convulsions and other seizures, with a variable expression in several members of the same pedigree, perhaps due to ionic channel dysfunction. SMEI could represent the most severe end of the spectrum.
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Epilepsias Mioclónicas/diagnóstico , Epilepsia Generalizada/diagnóstico , Convulsiones Febriles/diagnóstico , Adulto , Anciano , Niño , Preescolar , Cromosomas Humanos Par 19/genética , Cromosomas Humanos Par 2/genética , Epilepsias Mioclónicas/genética , Epilepsia Generalizada/genética , Humanos , Lactante , Italia , Linaje , Convulsiones Febriles/genéticaRESUMEN
We evaluate personality traits, anxiety and depression in a population of paediatric and adolescent patients, correlating personality characteristics with headache and sociodemographic variables. The clinical features of headache include specific personality traits. We report a clinical study of 57 patients (age 8-18 years), divided up as follows: 12 migraine with aura, 29 migraine without aura and 16 tension-type headache. One of Cattel's tests was administered to every patient; the Children's Depression Inventory test was administered to 53 patients and the Test Anxiety Inventory test to 43 subjects. The scores obtained by every patient in each test were correlated with the characteristics of headache and with sociodemographic data. We found that patients affected by idiopathic headache share some personality traits, mainly emotional rigidity and tendency to repress anger and aggression. These traits do not seem to be correlated with sociodemographic data and the duration of headache: we considered these as characteristic of migrainous patients.
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Cefalea/psicología , Personalidad , Adolescente , Ansiedad/complicaciones , Niño , Depresión/complicaciones , Femenino , Cefalea/complicaciones , Humanos , Masculino , Determinación de la Personalidad , Clase SocialRESUMEN
Developmental reading disability (dyslexia) has traditionally been attributed to impaired linguistic skills. Recent psychophysical data suggest that dyslexia may be related to a visual perceptual deficit. A few visual evoked potential (VEP) studies have addressed this hypothesis, but their results are far from consistent. We submitted 9 dyslexic subjects and 9 age- and sex-matched normal controls to checkerboard pattern reversal VEPs. The main experimental variables were: large (0.5 cycles per degree; cpd) and small (2 cpd) checks and two reversal frequencies (2.1 Hz and 8 Hz); mean luminance and contrast (60 cd/m2 and 50%, respectively) were kept constant in all four conditions. Transient VEP (2.1 Hz) parameters did not differ between controls and dyslexics at 2 cpd. At 0.5 cpd, N70 amplitude was significantly smaller and N70 latency significantly shorter in dyslexics. Amplitudes for the fundamental frequency (8 Hz), as well as for the second and third harmonics of the steady-state VEPs were smaller in dyslexics for both stimulus sizes. A discriminant analysis correctly classified each subject. Our data confirm the hypothesis of a perceptual deficit in dyslexic subjects. The abnormalities are related to spatial and temporal stimulus frequencies: they appear when large stimuli are presented, or when the stimulation frequency is high. These data support the hypothesis of selective magnocellular dysfunction in dyslexia.
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Dislexia/fisiopatología , Potenciales Evocados Visuales/fisiología , Adolescente , Niño , Electroencefalografía , Femenino , Humanos , Masculino , Reconocimiento Visual de Modelos/fisiología , Estimulación Luminosa , LecturaAsunto(s)
Distrofia Muscular de Duchenne/fisiopatología , Composición Corporal , Encéfalo/fisiopatología , Metabolismo Energético , Humanos , Músculo Esquelético/enzimología , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patología , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo I , DescansoRESUMEN
Continuous spikes and waves during slow sleep (CSWS) are a well-known EEG pattern that can be associated with cognitive and behavioural deterioration. We present the long-term clinical, neuropsychological and EEG follow-up of two patients who developed CSWS during childhood. In both the CSWS onset was followed immediately by rapid cognitive and behavioural deterioration. Later the CSWS fragmented or fluctuated and the spike-wave discharges diminished and this was associated with progressive clinical improvement. At the same time bilateral frontal EEG abnormalities appeared awake and in sleep. After the initial period of rapid cognitive and linguistic improvement both patients stabilised. The latest neuropsychological assessment showed a frontal syndrome. The presence of frontal EEG abnormalities superimposed on CSWS, their persistence after CSWS resolution and, in addition, the finding of subtle frontal-type neuropsychological alterations early in recovery may indicate poor long-term outcome.