Hereditary spastic paraplegia associated with thin corpus callosum.
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Autosomal recessive hereditary spastic paraplegia (AR-HSP) associated with thin corpus callosum was recently described in Japan, and most families were linked to chromosome 15 q13-15. We report two patients from two different Brazilian families with progressive gait disturbance starting at the second decade of life, spastic paraparesis, and mental deterioration. One patient presented cerebellar ataxia. Magnetic resonance imaging (MRI) of the head of both patients showed a thin corpus callosum. AR-HSP with a thin corpus callosum is a rare disorder, mainly described in Japanese patients. We found only 4 Caucasian families with AR-HSP with thin corpus callosum described in the literature. Further studies including additional Caucasian families of AR-HSP with thin corpus callosum are required to delineate the genetic profile of this syndrome in occidental countries. (+info)
Growth-associated protein-43 is required for commissural axon guidance in the developing vertebrate nervous system.
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Growth-associated protein-43 (GAP-43) is a major growth cone protein whose phosphorylation by PKC in response to extracellular guidance cues can regulate F-actin behavior. Here we show that 100% of homozygote GAP-43 (-/-) mice failed to form the anterior commissure (AC), hippocampal commissure (HC), and corpus callosum (CC) in vivo. Instead, although midline fusion was normal, selective fasciculation between commissural axons was inhibited, and TAG-1-labeled axons tangled bilaterally into Probst's bundles. Moreover, their growth cones had significantly smaller lamellas and reduced levels of F-actin in vitro. Likewise, 100% of GAP-43 (+/-) mice with one disrupted allele also showed defects in HC and CC, whereas the AC was unaffected. Individual GAP-43 (+/-) mice could be assigned to two groups based on the amount that PKC phosphorylation of GAP-43 was reduced in neocortical neurons. In mice with approximately 1% phosphorylation, the HC and CC were absent, whereas in mice with approximately 10% phosphorylation, the HC and CC were smaller. Both results suggest that PKC-mediated signaling in commissural axons may be defective. However, although Probst's bundles formed consistently at the location of the glial wedge, both GAP-43 (-/-) and GAP-43 (+/+) cortical axons were still repulsed by Slit-2 in vitro, precluding failure of this deflective signal from the glial wedge as the source of the phenotype. Nonetheless, the data show that a functional threshold of GAP-43 is required for commissure formation and suggests that failure to regulate F-actin in commissural growth cones may be related to inhibited PKC phosphorylation of GAP-43. (+info)
Two Japanese CADASIL families with a R141C mutation in the Notch3 gene.
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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary disease characterized by recurrent transient ischemic attacks (TIA) and strokes, and vascular dementia with Notch3 gene mutations as the cause of the disease. To date, there are only a few Japanese families ever reported with a mutation in the gene. Here, we report two more Japanese CADASIL families carrying a missense mutation in the Notch3 gene (R141C) with a unique lesion in the corpus callosum. This is the first report of two unrelated Japanese CADASIL families with a R141C mutation in the Notch3 gene. Although the disease is very rare among the Japanese population, our result suggests a possible relationship of this particular mutation (R141C) with the lesions of the corpus callosum. (+info)
Sound localization in callosal agenesis and early callosotomy subjects: brain reorganization and/or compensatory strategies.
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In order to evaluate the callosal involvement in sound localization, the present study examined the response accuracy of acallosal and early callosotomized subjects to monaural and binaural auditory targets presented in three-dimensional space. In these subjects, bilateral localization cues, such as interaural time and level differences, are integrated at the cortical and subcortical levels without the additional support of the callosal commissure. Because acallosal and early-callosotomized subjects have developed with this reduced source of binaural activation of cortical cells, they might have perfected their ability to use monaural sound localization cues. This hypothesis was tested by assessing localization performance under both binaural and monaural listening conditions. Five subjects with callosal agenesis, one callosotomized subject operated early in life and 19 control subjects were asked to localize broad-band noise bursts (BBNBs) of fixed intensity in the horizontal plane in an anechoic chamber. BBNBs were delivered through randomly selected loudspeakers. Two conditions were tested: (i) localization of a stationary sound source; and (ii) localization of a moving sound source. Listeners had to report the apparent stimulus location by pointing to its perceived position on a graduated perimeter. The results indicated that the acallosal subjects were less accurate than controls, but only in the binaural moving sound condition. More interestingly, in the monaural testing conditions, some of the acallosal subjects and the early-callosotomized subject performed significantly better than control subjects. This suggests that, because of the absence of the corpus callosum, these subjects compensate for their reduced access to cortically determined binaural cues by making more efficient use of monaural cues. (+info)
Abnormalities of the corpus callosum in first episode, treatment naive schizophrenia.
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BACKGROUND: Structural alterations in the association cortices as well as in the corpus callosum (CC) have been described in schizophrenia, and have been considered to reflect developmental abnormalities. Areas of primary and association cortices have been topographically mapped in the CC. OBJECTIVE: To investigate whether, in schizophrenia, there are alterations in CC subdivisions that connect association, but not primary, cortices, and also to see if the normative, developmentally mediated increase in CC size with age is absent in this disorder. METHODS: The midsagittal magnetic resonance imaging scans of 31 first episode, neuroleptic naive, schizophrenic patients, 12 non-schizophrenic, psychotic patients, and 31 healthy controls were compared. The total area of CC as well as that of anterior, middle and posterior genu, body, isthmus, and anterior, middle, and posterior splenii were measured. RESULTS: Patients with schizophrenia as a group had a smaller CC, anterior genu, anterior body, isthmus, and anterior splenium than normal controls. Furthermore, the age related increase in CC size seen in normal subjects was absent in the patients. CONCLUSIONS: The observed reductions in size in selected regions of CC suggest a reduction in axonal connections between the heteromodal association cortices, which typically involve small diameter fibres. Furthermore, the absence of an age related increase in CC size in patients with schizophrenia suggests a neurodevelopmental abnormality that may extend into adolescence and early adulthood. (+info)
Fetal pericallosal lipoma: US and MR findings.
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We report a case of fetal pericallosal lipoma occurring at the anterior interhemispheric fissure and associated with agenesis of the corpus callosum. During targeted prenatal ultrasonography at 26 weeks' gestation, the lesion was seen as a highly echogenic mass. MR imaging performed at 35 weeks' gestation and during the postnatal period revealed a pericallosal fatty mass and agenesis of the corpus callosum. (+info)
Fine mapping the candidate region for peripheral neuropathy with or without agenesis of the corpus callosum in the French Canadian population.
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Peripheral neuropathy with or without agenesis of the corpus callosum (ACCPN [MIM 2180000]) is an autosomal recessive disease characterised by progressive sensorimotor neuropathy, mental retardation, dysmorphic features and complete or partial agenesis of the corpus callosum. The ACCPN gene was mapped in 1996 to a 4 cM region on chromosome 15. We have since collected additional French Canadian (FC) families and typed a total of 11 polymorphic markers spanning approximately 18 cM on chromosome 15. Through the use of haplotype analysis we have confirmed the presence of a founder haplotype in the FC population, and identified critical recombinants which reduce the ACCPN candidate interval to a approximately 2 cM or 1000 Kb region flanked by markers D15S1040 and ACTC. Linkage disequilibrium analysis supports the haplotype data, and suggests that the ACCPN gene lies nearest to marker D15S1232. (+info)
Midline corpus callosum is a neuroanatomical focus of fetal alcohol damage.
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Prenatal exposure to high levels of alcohol often induces birth defects that combine morphological stigmata with neurological or neuropsychological deficits. But it has proved problematic to diagnose these syndromes in adolescents and adults, in whom the morphological signs are absent or attenuated, the behavioral deficits nonspecific, and the exposure history often difficult to reconstruct. Localizing the associated brain abnormalities might circumvent most of these difficulties. To this end, three-dimensional (3D) locations were recorded for 67 homologous points on or near the corpus callosum in magnetic resonance (MR) brain images from 60 adolescents and adults who were normal, 60 diagnosed with fetal alcohol syndrome, and 60 diagnosed with fetal alcohol effects. We combined the standard statistical approach to this type of geometric data, Procrustes analysis, with a multivariate strategy focusing on differences in variability. In this data set, the shape of the corpus callosum and its vicinity proves systematically much more variable in the alcohol-affected brains than in those of the normal subjects. From this excess variability follows a promising classification rule, having both high sensitivity (100 out of 117) and high specificity (49 out of 60) in this sample. The discrimination uses four landmark points and two summary scores of callosal outline shape. The information from the corpus callosum and vicinity, as viewed in MR brain images of full-grown subjects, may serve as a permanent record of the prenatal effects of alcohol, even in patients who are first suspected of these syndromes relatively late in life or who lack the facial signs of prenatal alcohol damage. The statistical pattern underlying the callosal diagnosis also leads to speculations on mechanisms of the prenatal damage. (+info)