RESUMEN
There is evidence of an association between thyroid hormones (TH) alterations and mental dysfunctions related to procedural and working memory functions, but the physiological link between these domains is still under debate, also for the presence of age as a confounding factor. Thus, we investigated the TH tuning of cerebral functions in young females affected by the borderline condition of subclinical hypothyroidism (SH) and in euthyroid females of the same age. The experiment consisted in the characterization of the affective state and cognitive abilities of the subjects by means of specific neuropsychological questionnaires, and of brain activity (EEG) in resting state and during the passive viewing of emotional video-clips. We found that SH had i) increased anxiety for Physical Danger; ii) better scores for both Mental Control and no-working-memory-related functions; iii) association between anxiety for Physical Danger and fT4 levels. Thus, in young adults, SH increases inward attention and paradoxically improves some cognitive functions. In addition, self-assessed questionnaires showed that SH had a greater susceptibility to unpleasant emotional stimulation. As for EEG data, SH compared to controls showed: i) reduction of alpha activity and of gamma left lateralization in resting state; ii) increased, and lateralized to the right, beta2 activity during stimulations. Both results indicated that SH have higher levels of arousal and greater susceptibility to negative emotion than controls. In conclusion, our study indicates that minimal changes in TH levels produce subtle but well-defined mental changes, thus encouraging further studies for the prediction of pathology evolution.
Asunto(s)
Encéfalo/metabolismo , Encéfalo/fisiopatología , Hipotiroidismo/complicaciones , Hipotiroidismo/patología , Estimulación Acústica , Adolescente , Adulto , Trastornos del Conocimiento/etiología , Electroencefalografía , Potenciales Evocados Auditivos/fisiología , Femenino , Humanos , Hipotiroidismo/sangre , Modelos Lineales , Trastornos de la Memoria/etiología , Memoria a Corto Plazo , Trastornos del Humor/etiología , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Psicometría , Encuestas y Cuestionarios , Hormonas Tiroideas/sangre , Tirotropina/sangre , Aprendizaje Verbal , Adulto JovenRESUMEN
AIM: Sensorineural hearing loss (SNHL) is complicated by additional disabilities in about 30% of cases, but the epidemiology of associated disorders, in terms of type, frequency and aetiology is still not clearly defined. Additional disabilities in a deaf child have important consequences in assessing and choosing a therapeutic treatment, in particular when considering cochlear implantation (CI) or hearing aids (HA). The aim of this paper was to evaluate frequency, type and severity of additional neurodevelopmental disabilities in children with profound bilateral sensorineural hearing loss and to investigate the relationship between disability and the etiology of deafness. METHODS: Eighty children with profound bilateral sensorineural hearing loss (mean age 5.4 years) were investigated by means of a diagnostic protocol including clinical, neurodevelopmental, and audiological procedures together with genetic and neurometabolic tests and neuroradiological investigation by brain MRI. RESULTS: Fifty-five percent of the sample exhibited one or more disabilities in addition to deafness, with cognitive, behavioural-emotional and motor disorders being the most frequent. The risk of additional disabilities varied according to aetiology, with a higher incidence in hereditary syndromic deafness, in cases due to pre-perinatal pathology (in comparison to unknown and hereditary non syndromic forms) and in the presence of major brain abnormalities at MRI. CONCLUSION: Our results suggest that the aetiology of deafness may be a significant risk indicator for the presence of neuropsychiatric disorders. A multidimensional evaluation, including aetiological, neurodevelopmental and MRI investigation is needed for formulating prognosis and for planning therapeutic intervention, especially in those children candidated to cochlear implant.
Asunto(s)
Sordera/diagnóstico , Sordera/etiología , Discapacidades del Desarrollo/complicaciones , Discapacidades del Desarrollo/diagnóstico , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/etiología , Pruebas Neuropsicológicas , Adolescente , Niño , Preescolar , Implantación Coclear , Sordera/complicaciones , Sordera/epidemiología , Sordera/terapia , Discapacidades del Desarrollo/epidemiología , Femenino , Audífonos , Pérdida Auditiva Sensorineural/complicaciones , Pérdida Auditiva Sensorineural/epidemiología , Pérdida Auditiva Sensorineural/terapia , Humanos , Incidencia , Lactante , Italia/epidemiología , Imagen por Resonancia Magnética , Masculino , Valor Predictivo de las Pruebas , Prevalencia , Muestreo , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
We describe the clinical and molecular features of a child harboring a novel mutation in SLC6A8 gene in association with a milder phenotype than other creatine transporter (CT1) deficient patients (OMIM 300352) [1-7]. The mutation c.757 G>C p.G253R in exon 4 of SLC6A8 was hemizygous in the child, aged 6 years and 6 months, who showed mild intellectual disability with severe speech and language delay. His carrier mother had borderline intellectual functioning. Although the neurochemical and biochemical parameters were fully consistent with those reported in the literature for subjects with CT1 deficit, in our patient within a general cognitive disability, a discrepancy between nonverbal and verbal skills was observed, confirming the peculiar vulnerability of language development under brain Cr depletion.
Asunto(s)
Discapacidad Intelectual/genética , Trastornos del Lenguaje/genética , Proteínas de Transporte de Membrana/genética , Mutación , Adulto , Secuencia de Bases , Niño , Femenino , Humanos , Discapacidad Intelectual/diagnóstico , Trastornos del Lenguaje/diagnóstico , Masculino , Datos de Secuencia Molecular , Alineación de SecuenciaRESUMEN
The results of medical specialist consultations sampled from several rural clinics located throughout India indicate that remote expert opinions can improve the speed and accuracy of diagnosis. Central to this presentation is a description of how real-time and store & forward telemedicine services can be provided to rural populations over hybrid networks made up of ISDN, POTS, VSAT, cellular, and Cable Internet connections. A model for meeting the specialized medical needs of developing countries will be highlighted. Descriptions, examples, and benefits of how Browser-based client-server architectures are being used in over 20 locations in India and Mexico for triaging real-time vital signs, DICOM images, audio & video, and clinical text information will be highlighted.
RESUMEN
Neurotrophin nerve growth factor (NGF) has been suggested to be involved in age-related neurodegenerative diseases, but no transgenic model is currently available to study this concept. We have obtained transgenic mice expressing a neutralizing anti-NGF recombinant antibody, in which the levels of antibodies are three orders of magnitude higher in adult than in newborn mice [F.R., S. C. , A.C., E. Di Daniel, J. Franzot, S. Gonfloni, G. Rossi, N. B. & A. C. (2000) J. Neurosci., 20, 2589-2601]. In this paper, we analyze the phenotype of aged anti-NGF transgenic mice and demonstrate that these mice acquire an age-dependent neurodegenerative pathology including amyloid plaques, insoluble and hyperphosphorylated tau, and neurofibrillary tangles in cortical and hippocampal neurons. Aged anti-NGF mice also display extensive neuronal loss throughout the cortex, cholinergic deficit in the basal forebrain, and behavioral deficits. The overall picture is strikingly reminiscent of human Alzheimer's disease. Aged anti-NGF mice represent, to our knowledge, the most comprehensive animal model for this severe neurodegenerative disease. Also, these results demonstrate that, in mice, a deficit in the signaling and/or transport of NGF leads to neurodegeneration.
Asunto(s)
Enfermedad de Alzheimer/etiología , Encéfalo/patología , Factor de Crecimiento Nervioso/inmunología , Envejecimiento , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Animales , Anticuerpos/sangre , Colina O-Acetiltransferasa/metabolismo , Trastornos del Conocimiento/etiología , Fragmentación del ADN , Humanos , Trastornos de la Memoria/etiología , Ratones , Ratones Transgénicos , Sistema Nervioso Parasimpático/fisiología , FosforilaciónRESUMEN
The disruption of the nerve growth factor (NGF) gene in transgenic mice leads to a lethal phenotype (Crowley et al., 1994) and hinders the study of NGF functions in the adult. In this study the phenotypic knockout of NGF in adult mice was achieved by expressing transgenic anti-NGF antibodies, under the control of the human cytomegalovirus promoter. In adult mice, antibody levels are 2000-fold higher than in newborns. Classical NGF targets, including sympathetic and sensory neurons, are severely affected. In the CNS, basal forebrain and hippocampal cholinergic neurons are not affected in the early postnatal period, whereas they are greatly reduced in the adult (55 and 62% reduction, respectively). Adult mice show a reduced ability in spatial learning behavioral tasks. Adult, but not neonatal, transgenic mice further show a new phenotype at the level of peripheral tissues, such as apoptosis in the spleen and dystrophy of skeletal muscles. The analysis of this novel comprehensive transgenic model settles the controversial issue regarding the NGF dependence of cholinergic neurons in adult animals and reveals new NGF functions in adult non-neuronal tissues. The results demonstrate that the decreased availability of NGF in the adult causes phenotypic effects via processes that are at least partially distinct from early developmental effects of NGF deprivation.