Thalamic nuclear abnormalities as a contributory factor in sudden cardiac deaths among patients with schizophrenia.

Patients with schizophrenia have a two- to three-fold increased risk of premature death as compared to patients without this disease. It has been established that patients with schizophrenia are at a high risk of developing cardiovascular disease. Moreover, an important issue that has not yet been explored is a possible existence of a "cerebral" focus that could trigger sudden cardiac death in patients with schizophrenia. Along these lines, several structural and functional alterations in the thalamic complex are evident in patients with schizophrenia and have been correlated with the symptoms manifested by these patients. With regard to abnormalities on the cellular and molecular level, previous studies have shown that schizophrenic patients have fewer neuronal projections from the thalamus to the prefrontal cortex as well as a reduced number of neurons, a reduced volume of either the entire thalamus or its subnuclei, and abnormal glutamate signaling. According to the glutamate hypothesis of schizophrenia, hypofunctional corticostriatal and striatothalamic projections are directly involved in the pathophysiology of the disease. Animal and post-mortem studies have provided a large amount of evidence that links the sudden unexpected death in epilepsy (SUDEP) that occurs in patients with schizophrenia and epilepsy to thalamic changes. Based on the results of these prior studies, it is clear that further research regarding the relationship between the thalamus and sudden cardiac death is of vital importance.

Thalamic nuclear abnormalities as a contributory factor in sudden cardiac deaths among patients with schizophrenia

Patients with schizophrenia have a two- to three-fold increased risk of premature death as compared to patients without this disease. It has been established that patients with schizophrenia are at a high risk of developing cardiovascular disease. Moreover, an important issue that has not yet been explored is a possible existence of a "cerebral" focus that could trigger sudden cardiac death in patients with schizophrenia. Along these lines, several structural and functional alterations in the thalamic complex are evident in patients with schizophrenia and have been correlated with the symptoms manifested by these patients. With regard to abnormalities on the cellular and molecular level, previous studies have shown that schizophrenic patients have fewer neuronal projections from the thalamus to the prefrontal cortex as well as a reduced number of neurons, a reduced volume of either the entire thalamus or its subnuclei, and abnormal glutamate signaling. According to the glutamate hypothesis of schizophrenia, hypofunctional corticostriatal and striatothalamic projections are directly involved in the pathophysiology of the disease. Animal and post-mortem studies have provided a large amount of evidence that links the sudden unexpected death in epilepsy (SUDEP) that occurs in patients with schizophrenia and epilepsy to thalamic changes. Based on the results of these prior studies, it is clear that further research regarding the relationship between the thalamus and sudden cardiac death is of vital importance.

Links between abnormal brain structure and cognition in holoprosencephaly.

Converging information on medical issues, motor ability, and cognitive outcomes is essential when addressing long-term clinical management in children with holoprosencephaly. This study considered whether adding more informative structural indices to classic holoprosencephaly categories would increase prediction of cognitive outcomes. Forty-two children with holoprosencephaly were examined to determine the association of deep gray nuclei abnormalities with cognitive abilities and the effect of motor skill deficits on cognitive performance. Additionally, a cognitive profile was described using the Carter Neurocognitive Assessment, an experimental diagnostic instrument designed specifically for young children with severe neurodevelopmental dysfunction. Findings indicated that nonseparation of the deep gray nuclei was significantly associated with the cognitive construct of vocal communication, but not with the cognitive constructs of social awareness, visual attention, or auditory comprehension. Importantly, motor skill deficits did not significantly affect performance on the Carter Neurocognitive Assessment. This study is the first investigation to provide a descriptive overview of specific cognitive skills in this group of children. The results also strongly suggest that this feature of the brain's structure does not predict all aspects of neurodevelopmental function. These findings contribute a critical component to the growing body of knowledge regarding the medical and clinical outcomes of children with holoprosencephaly.

Severe defects in dorsal thalamic development in low-density lipoprotein receptor-related protein-6 mutants.

Mice with mutations in the Wnt coreceptor low-density lipoprotein receptor-related protein-6 (LRP6) have a smaller and severely disorganized dorsal thalamus and lack thalamocortical projections. Using molecular markers, we showed that most dorsal thalamic and epithalamic neurons were missing, and most of the major dorsal thalamic nuclei were not identifiable. However, the ventral thalamus was essentially unaffected, although the dorsal thalamic defect leads to rostral displacement of portions of the ventral thalamus. Analysis of younger embryos showed that epithalamic and dorsal thalamic neurons were not produced at early stages of development, whereas ventral thalamic neurons were still produced. These defects were accompanied by improper formation of the boundary between dorsal and ventral thalamus, the zona limitans interthalamica (ZLI). Furthermore, the expression of an early marker of posterior forebrain development that marks the compartment from the midbrain-hindbrain junction to the ZLI (including the future dorsal thalamus, pretectum, and midbrain) was disrupted, supporting the idea that diencephalic development is abnormal from very early in embryogenesis. This study provides compelling in vivo evidence that thalamic development requires normal activity of the LRP6-mediated canonical Wnt signaling pathway.

Los síndromes de lesión talámica

En la unidad de Neurología del Centro Hospitalario San Juan de Dios de Bogotá, durante cuatro años (1986 a 1989), se estudiaron en forma consecutiva 25 pacientes con lesiones talámaticas no fatales. Se registraron los hallazgos neurológicos, neurosicológicos y neurooftalmológicos y los diagnósticos se confirmaron por tomografía computarizada (TC). Fueron 14 mujeres y 11 varones con una edad promedio de 52.5 y un rango de 25 a 84 años. La lesión talámica fue de origen vascular en 24 casos, ocho por infarto isquémico, cuatro por infarto hemorrágico y 12 con hematomas parenquimatosos. Diecisiete pacientes tenían hipertensión arterial sistémica y el único factor de riesgo en otros dos era el consumo de cocaína base (basuco). Ocho infartos se presentaron en el tálamo derecho, 12 en el izquierdo y cinco pacientes tuvieron lesiones bilaterales, uno de ellos con un glioma complobado por biopsia. En 5 pacientes con lesiónes bilateral se observó el síndrome del "Tope" de la arteria basilar, por compromiso del pedículo retromamilar; en todos ellos encontramos alteraciones sensitivomotoras, cerebelosas, oculomotoras bilaterales y demencia. Solamente un paciente presentó el clasicó síndrome de hiperpatía (Dejerine-Roussy). En los restantes se observaron asociaciones de síndromes sensitivomotores, cerebelosos, neurooftalmológicos, neuropsicológicos, y del comportamiento motor que remedan con frecuencia los hallazgos clínicos de la alteración cortical frontal, temporal o parietal.

An abnormal retinal projection to the lateral posterior nucleus in micrencephalic rats.

The retinofugal projections of albino rats made micrencephalic by prenatal exposure to the cytotoxic teratogen methylazoxymethanol acetate (MAM Ac) have been examined. The only abnormality noted was an increased projection to the lateral posterior nucleus of the thalamus in rats exposed to MAM Ac on embryonic day 15. The relatively normal retinofugal projections were surprising in view of the extensive damage induced by prenatal exposure to this drug.

Alcohol embryo- and fetopathy. Neuropathology of 3 children and 3 fetuses.

Maternal chronic ethanol abuse during pregnancy causes malformations of the offspring. Three children (aged 6 months, 9 months, 4 1/2 years) and 3 fetuses (17th, 18th, and 20th gestational week) showed a wide spectrum of disorders ranging from severe dysraphic state, arhinencephaly, porencephaly, agenesis of corpus callosum, a range from hydranencephaly to microdysplasias (p.e. reduced gyration of dentate nucleus and inferior olives), and a range from gastrochisis or congenital heart defects to craniofacial dysmorphogenesis and palmar crease anomalies. The patterns of the cerebral malformations were not as uniform as the clinical phenotype of the alcohol embryopathy. The observations did not support the assumption that there exists a specific period for alcohol teratogenicity.

Thalamic lesions during the development period and their clinical correlation.

28 autopsy cases were investigated in which the thalamus was impaired in early life, i.e. prenatal, perinatal, and postnatal (under 1 year of age). The thalamus is vulnerable to brain damage in the perinatal and early postnatal period. Lesions in the thalamus are severe in the DM, PL and VPL, and moderate in the VL and pulvinar thalamus. The anterior nuclei and center median show little change. Many of the cases with athetoid movements have complicated thalamic lesions in addition to those of the basal ganglia. In one patient who showed athetosis as a sequela of encephalitis japonica, the VL and PL in the thalamus were involved severely; in contrast the basal ganglia revealed very slight changes.