Congenital bilateral perisylvian syndrome: familial occurrence, clinical and psycholinguistic aspects correlated with MRI.

OBJECTIVE: Congenital bilateral perisylvian syndrome (CBPS) is frequently caused by polymicrogyria (PMG). The aim of this study was to correlate the clinical and psycholinguistic aspects with neuroradiological data of patients with CBPS. METHODS: Thirty-one patients were studied. We performed a clinical investigation of the patients and their families, including MRI scanning, neuropsychological tests and language evaluation. RESULTS: The statistical analysis showed that: a) prenatal events are associated with the non-familial type of PMG; b) diffuse PMG is associated with pseudobulbar signs, as opposed to BPPP; c) motor deficit is associated with diffuse PMG; d) epilepsy is equally present in patients with both familial or non-familial PMG, but is more frequently seen in patients with diffuse PMG; e) dyslexia and SLI can be a feature of both the diffuse or BPPP, and either familial or sporadic cases of PMG. CONCLUSIONS: The severity of clinical manifestations in CBPS is correlated with the extent of cortical involvement. Most patients with CBPS have a history of speech delay or language difficulties and no epilepsy. Dyslexia can be found in patients with PMG.

Developmental language disorder associated with polymicrogyria.

BACKGROUND: Subtle disorders of neuronal migration occur in the brains of some dyslexic patients who presented developmental language disorder (DLD) during early childhood. OBJECTIVE: To investigate a possible neuroanatomical substrate based on neuroimaging evaluation in children with DLD. METHODS: The authors obtained psychological assessment, language evaluation, neurologic examination, and neuroimaging investigation. Inclusion criteria were as follows: children should be at least 4 years of age; primary complaint of language delay; normal hearing; IQ >70; and an informed consent form signed by parents or guardians. Exclusion criteria were severe motor and cognitive handicap. RESULTS: Fifteen children met all inclusion criteria. Ages ranged from 4 to 14 years and 11 were boys. Six patients presented diffuse polymicrogyria (PMG) around the entire extent of the sylvian fissure on MRI, and they had severe clinical manifestation of DLD: they did not speak at all or had mixed phonologic-syntactic deficit syndrome. Six children presented PMG restricted to the posterior aspects of the parietal regions, and they had a milder form of DLD: mainly phonologic programming deficit syndrome. The other three children had different imaging findings. CONCLUSIONS: Developmental language disorder can be associated with polymicrogyria and the clinical manifestation varies according to the extension of cortical abnormality. A subtle form of posterior parietal polymicrogyria presenting as developmental language disorder is a mild form of perisylvian syndrome.

Chloramphenicol induces apoptosis in the developing brain.

Programmed cell death was studied in the superior colliculus of the developing rat brain following injections of chloramphenicol. Neonatal rats were either subject to unilateral eye removal or left untouched. Following a 3-h post-operative survival, the animals were perfused with fixatives and frozen sections of their brains were examined for apoptosis after either neutral-red staining, in situ nick-end labeling of fragmented DNA, or immunocytochemistry to activated caspase-3. Chloramphenicol induced apoptosis in control brains and potentiated cell death in deafferented superior colliculi. The results show that CMP has a general pro-apoptotic effect in the developing brain.

Death in a dish: controls of apoptosis within the developing retinal tissue.

Studies of programmed cell death in the developing retina in vitro are currently reviewed. The results of inhibiting protein synthesis in retinal explants indicate two mechanisms of apoptosis. One mechanism depends on the synthesis of positive modulators ('killer proteins'), while a distinct, latent mechanism appears to be continuously blocked by negative modulators. Extracellular modulators of apoptosis include the neurotrophic factors NT-4 and BDNF, while glutamate may have either a positive or a negative modulatory action on apoptosis. Several protein kinases selectively modulate apoptosis in distinct retinal layers. Calcium and nitric oxide were also shown to affect apoptosis in the developing retinal tissue. The protein c-Jun was found associated with apoptosis in various circumstances, while p53 seems to be selectively expressed in some instances of apoptosis. The results indicate that the sensitivity of each retinal cell to apoptosis is controlled by multiple, interactive, cell type- and context-specific mechanisms. Apoptosis in the retina depends on a critical interplay of extracellular signals delivered through neurotrophic factors, neurotransmitters and neuromodulators, several signal transduction pathways, and the expression of a variety of genes.

Death in dish: controls of apoptosis within the developing retinal tissue

Studies of programmed cell death in the developing retina in vitro are currently reviewed. The results of inhibiting protein synthesis in retinal explants indicate two mechanisms of apoptosis. One mechanism depends on the synthesis of positive modulators ('killer proteins'), while a distinct, latent mechanism appears to be continuously blocked by negative modulators. Extracellular modulators of apoptosis include the neurotrophic factors NT-4 and BDNF, while glutamate may have either a positive or a negative modulatory action on apoptosis. Several protein kinases selectively modulate apoptosis in distinct retinal layers. Calcium and nitric oxide were also shown to affect apoptosis in the developing retianl tissue. The protein c-Jun was found associated with apoptosis in various circumstances, while p53 seems to be selectively expressed in some instances of apoptosis. The results indicate that the sensitivity of each retinal cell to apoptosis is controlled by multiple, interactive, cell type- and context-specific mechanisms. Apoptosis in the retina depends on a critical interplay of extracellular signals delivered through neurotrophic factors, neurotransmitters and neuromodulators, several signal transduction pathways, and the expression of a variety of genes.