Neurodevelopmental disorders in children with severe to profound sensorineural hearing loss: a clinical study.
ABSTRACT The effects of sensorineural hearing loss (SNHL) are often complicated by additional disabilities, but the epidemiology of associated disorders is not clearly defined. The aim of this study was to evaluate the frequency and type of additional neurodevelopmental disabilities in a sample of children with SNHL and to investigate the relation between these additional disabilities and the aetiology of deafness.
One hundred children with severe/profound SNHL (60 males, 40 females; mean age 5 y 7 mo, SD 3 y 6 mo, range 8 mo-16 y) were investigated using a diagnostic protocol including neurodevelopmental, genetic, neurometabolic, and brain magnetic resonance imaging (MRI) assessment.
Forty-eight per cent of the sample exhibited one or more additional disabilities, with cognitive, behavioural-emotional, and motor disorders being the most frequent. The risk of additional disabilities varied according to the type of aetiology. Thirty-seven out of 80 individuals with available MRIs showed signal abnormalities, in particular brain malformations (46%) and white matter abnormalities (54%). Frequency and type of disability were associated with aetiology (p=0.015) and MRI data (p<0.001).
A multidimensional evaluation, including aetiological, neurodevelopmental, and MRI investigation, is needed for planning therapeutic intervention, such as cochlear implantation in children with severe to profound hearing impairment. The aetiology of deafness is a relevant risk indicator for the presence of an associated disorder.
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ABSTRACT: High-resolution magnetic resonance studies are an important tool in the investigation of the etiology of childhood sensorineural hearing loss. An added benefit with magnetic resonance is the ability to screen the central nervous system for findings which may adversely affect the neurodevelopmental outcome of these children. To determine the proportion of cases and significance of associated intracranial abnormalities as detected by central nervous system high-resolution magnetic resonance imaging in children with profound sensorineural hearing loss. Retrospective chart review of children undergoing evaluation for cochlear implantation in a tertiary care academic children's hospital with high-resolution magnetic resonance of the temporal bone and brain during a 21 month period. Magnetic resonance studies were interpreted by an experienced senior neuroradiologist blinded to the identity and clinical data of the patients. Forty patients were identified. All had the same magnetic resonance study consisting of a 3D high-resolution sequence through the temporal bone as well as a T1 sagittal and T2 axial screening sequence of the brain. Eight patients (20%) showed significant brain abnormalities by magnetic resonance imaging ranging from myelination delays to migrational anomalies. Temporal bone abnormalities were not seen. Three patients with Connexin-26 mutations had no associated brain abnormalities by magnetic resonance. A significant proportion of our patients being investigated by magnetic resonance imaging for profound sensorineural hearing loss show migrational abnormalities of the central nervous system, suggesting a central origin to their hearing loss. Some of these findings may result in neurodevelopmental delay and hence, negatively impact the success of cochlear implantation. We propose that magnetic resonance imaging of the temporal bone as part of the evaluation protocol for cochlear implantation in children should include central nervous system screening.International Journal of Pediatric Otorhinolaryngology 06/2006; 70(5):863-8. · 1.35 Impact Factor
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ABSTRACT: To document progress and benefit of multi-handicapped children using cochlear implants. The evaluation of auditory responses to speech (EARS) test battery was performed on the children in this study at regular intervals following implantation. All children went through individually tailored intensive audiological rehabilitation programs following cochlear implantation. Individual results from ten multi-handicapped children receiving cochlear implants are presented in this paper. The majority of children in this study are successful implant users. Whenever possible, test scores are included as well as subjective case reports. Providing multi-handicapped children with cochlear implants can result in substantial benefit for both the child and parents. Multi-handicapped children are not contraindicated for cochlear implantation, although not all are considered to be good candidates.International Journal of Pediatric Otorhinolaryngology 01/2001; 56(3):169-74. · 1.35 Impact Factor
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ABSTRACT: Periventricular heterotopia (PH) is a disorder characterized by neuronal nodules, ectopically positioned along the lateral ventricles of the cerebral cortex. Mutations in either of two human genes, Filamin A (FLNA) or ADP-ribosylation factor guanine exchange factor 2 (ARFGEF2), cause PH (Fox et al. in 'Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia'. Neuron, 21, 1315-1325, 1998; Sheen et al. in 'Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex'. Nat. Genet., 36, 69-76, 2004). Recent studies have shown that mutations in mitogen-activated protein kinase kinase kinase-4 (Mekk4), an indirect interactor with FlnA, also lead to periventricular nodule formation in mice (Sarkisian et al. in 'MEKK4 signaling regulates filamin expression and neuronal migration'. Neuron, 52, 789-801, 2006). Here we show that neurons in post-mortem human PH brains migrated appropriately into the cortex, that periventricular nodules were primarily composed of later-born neurons, and that the neuroependyma was disrupted in all PH cases. As studied in the mouse, loss of FlnA or Big2 function in neural precursors impaired neuronal migration from the germinal zone, disrupted cell adhesion and compromised neuroepithelial integrity. Finally, the hydrocephalus with hop gait (hyh) mouse, which harbors a mutation in Napa [encoding N-ethylmaleimide-sensitive factor attachment protein alpha (alpha-SNAP)], also develops a progressive denudation of the neuroepithelium, leading to periventricular nodule formation. Previous studies have shown that Arfgef2 and Napa direct vesicle trafficking and fusion, whereas FlnA associates dynamically with the Golgi membranes during budding and trafficking of transport vesicles. Our current findings suggest that PH formation arises from a final common pathway involving disruption of vesicle trafficking, leading to impaired cell adhesion and loss of neuroependymal integrity.Human Molecular Genetics 12/2008; 18(3):497-516. · 7.69 Impact Factor