Educational level as a modulator of cognitive performance and neuropsychyatric features in Parkinson disease.

OBJECTIVES: To test a possible association between the educational level (EL), cognitive performance, and neuropsychiatric features in Parkinson disease (PD). BACKGROUND: An inverse association has been reported between EL and cognitive dysfunction in patients with senile dementia of Alzheimer type but it is yet unsettled whether education has a similar effect on cognition in PD. METHODS: Seventy-two PD patients (45 males, mean age 68.7+/-11.6 y) underwent a detailed neurologic examination, a battery of neuropsychologic tests, and questionnaires for the evaluation of psychosis, sleep disturbances, and depression. According to the number of educational years, patients were divided into 3 groups: low EL (0 to 8 y), (15 patients), intermediate EL (9 to 12 y) (28 patients), and high EL (>/=13 y) (29 patients). RESULTS: Patients with a higher EL had a better cognitive function and an association was found between the patients' EL and their scores in various neuropsychologic tests mainly those sensitive to frontal lobe dysfunction. Low education was associated with an increased risk for hallucinations and a trend for more depression, delusions, and sleep disturbances. CONCLUSIONS: The association between high educational attainment and the lower risk of cognitive dysfunction suggest that education might modulate cognitive performance in PD.     

Sevoflurane versus Halothane: Postoperative Maladaptive Behavioral Changes: A Randomized, Controlled Trial

Background: The authors conducted a double-blind, randomized, controlled trial to determine whether the use of sevoflurane in children undergoing anesthesia and surgery results in a higher incidence of postoperative maladaptive behavioral changes as compared with halothane.

Methods: Children and their parents (n = 102) were randomly assigned to either a halothane group (n = 50) or a sevoflurane group (n = 52). The intraoperative anesthetic protocol was strictly controlled, and the postoperative analgesic consumption and pain levels were recorded. The effect of the group assignment on emergence status and maladaptive postoperative behavioral changes was assessed both by validated psychological measures and physiologic instruments (actigraphy) on postoperative days 1-7. Anxiety of the parent and child was also assessed, as was the child's postoperative recovery (Recovery Inventory).

Results: There were no group differences in preoperative state anxiety, postoperative analgesic requirements, postoperative pain, or the incidence of emergence delirium (P = not significant). Two-way repeated-measures analysis of variance showed no group differences in the incidence of postoperative maladaptive behaviors (F4,72 = 0.60, P = 0.701) or actigraphic variables such as percent sleep, number of night awakenings, and night awakenings that lasted for more than 5 min (P = not significant).     

Unsupervised fuzzy clustering analysis supports behavioral cutoff criteria in an animal model of posttraumatic stress disorder.

BACKGROUND: Unsupervised fuzzy clustering (UFC) analysis is a mathematical technique that groups together objects in the multidimensional feature space according to a specified similarity measurement, thereby yielding clusters of similar data points that can be represented by a set of prototypes or centroids. METHODS: Since clinical studies of mental disorders distinguish between affected and unaffected individuals, we designed an inclusion/exclusion criteria (cutoff behavioral criteria [CBC]) approach for animal behavioral studies. The effect of classifying the study population into clearly affected versus clearly unaffected individuals according to behaviors on two behavioral paradigms was statistically significant. RESULTS: Here the raw data from previous studies were subjected to UFC algorithms as a means of objectively testing the validity of the concept of the CBC for our experimental model. The first UFC algorithm yielded two clearly discrete clusters, found to consist almost exclusively of the exposed animals in the one and unexposed animals in the other. The second algorithm yielded three clusters corresponding to animals designated as clearly affected, partially affected, and clearly unaffected. The algorithm for physiological data in addition to behavioral data failed to elicit discrete clusters. CONCLUSIONS: The UFC analysis yielded data that support the conceptual contention of the CBC and lends additional validity to our previous behavioral studies.     

Human monoclonal antibodies against amyloid-beta from healthy adults

Two anti-amyloid-beta human antibody-producing cell lines were established from amyloid-beta (Abeta)-selected lymphocytes from peripheral blood of healthy adults. ELISA and Western blot analysis showed that the monoclonal antibodies bound with high affinity to the 43 amino acid-long amyloid-beta peptide. The antigen epitope of these antibodies encountered within amino acids 1-16 of the amyloid-beta peptide. The antibodies did not bind to several immunoglobulin light chain amyloids (AL) and amylin. One of the monoclonals was tested by immunohistochemistry for the binding to frozen sections of brains derived from patients with Alzheimer's disease. It specifically and intensively stained diffuse and core amyloid-beta plaques; whereas, sections from normal brains were not stained. Concomitant staining with a commercial mouse anti-amyloid-beta monoclonal antibody co-localized with that of the human antibody. Simultaneous staining with the human antibody and Congo red implied that the antibody binds primarily to an early immature form of beta-amyloid. Human monoclonal antibodies, which resemble physiologically normal non-pathogenic and possibly protective antibodies in healthy adults, might be attractive candidates for immune therapy of Alzheimer's disease.     

Molecular characterization of a 1p36 chromosomal duplication and in utero interference define ENO1 as a candidate gene for polymicrogyria

While chromosome 1p36 deletion syndrome is one of the most common terminal subtelomeric microdeletion syndrome, 1p36 microduplications are rare events. Polymicrogyria (PMG) is a brain malformation phenotype frequently present in patients with 1p36 monosomy. The gene whose haploinsufficiency could cause this phenotype remains to be identified. We used high-resolution arrayCGH in patients with various forms of PMG in order to identify chromosomal variants associated to the malformation and characterized the genes included in these regions in vitro and in vivo. We identified the smallest case of 1p36 duplication reported to date in a patient presenting intellectual disability, microcephaly, epilepsy, and perisylvian polymicrogyria. The duplicated segment is intrachromosomal, duplicated in mirror and contains two genes: enolase 1 (ENO1) and RERE, both disrupted by the rearrangement. Gene expression analysis performed using the patient cells revealed a reduced expression, mimicking haploinsufficiency. We performed in situ hybridization to describe the developmental expression profile of the two genes in mouse development. In addition, we used in utero electroporation of shRNAs to show that Eno1 inactivation in the rat causes a brain development defect. These experiments allowed us to define the ENO1 gene as the most likely candidate to contribute to the brain malformation phenotype of the studied patient and consequently a candidate to contribute to the malformations of the cerebral cortex observed in patients with 1p36 monosomy.Subject terms: Gene regulation, Genetics research     

Immunization with cholinergic cell bodies induces histopathological changes in rat brains

We have previously shown that sera from patients with Alzheimer’s disease (AD) contain antibodies to the cell bodies (perikarya; PK) of purely cholinergicTorpedo neurons, and that repeated immunization of rats with this neuronal preparation for over a year induces learning and memory impairments. In the present study, we examined the brain morphology of cholinergic PK immunized rats relative to controls. Immunohistochemical studies of the brains of these rats revealed the accumulation of IgG in specific areas, such as, the hippocampus. Parallel histochemical studies demonstrated significant changes in the hippocampus, and in white matter areas. They included large vacuoles and necrotic nuclei in the granular layer of the dentate gyrus, tangle-like appearance in some pyramidal neurons of the hippocampus, and vacuolar degeneration accompanied by oligodendroglia hypertrophy in white matter tracts, such as, the corpus callosum and fimbria. In contrast, immunization withTorpedo cholinergic nerve terminals, that has no cognitive effects on the rat, also did not induce brain morphological changes. These findings suggest that the learning and memory deficits induced by immunizing rats with cholinergic PK are related to the observed brain morphological changes, and support the hypothesis that the antibodies to cholinergic neurons found in the sera of AD patients may play a role in neuronal degeneration in this disease.     

Remission of Tardive Dystonia with ECT

A 30-year-old patient with tardive dystonia, who had failed to respond to cessation of neuroleptics, placebo, diazepam, biperiden, propranolol, and clonidine, had an impressive response to courses of electroconvulsive therapy (ECT) on three successive trials.     

Setting apart the affected: the use of behavioral criteria in animal models of post traumatic stress disorder.

Post-traumatic stress disorder (PTSD) affects about 20-30% of exposed individuals. Clinical studies of PTSD generally employ stringent criteria for inclusion in study populations, and yet in animal studies the data collection and analysis are generally expressed as a function of exposed vs nonexposed populations, regardless of individual variation in response. Prior data support an approach to animal models analogous to inclusion criteria in clinical studies. This series of studies sought to assess prevalence rates of maladaptive vs adaptive responses determined according to a more stringent approach to the concept of inclusion/exclusion criteria (cutoff behavioral criteria-CBC), consisting of two successive behavioral tests (elevated plus maze and acoustic startle response tests). The rats were exposed to stressors in two different paradigms; exposure to a predator and underwater trauma. The prevalence rates of maladaptive responses to stress in these two distinct models dropped over time from 90% in the acute phase to 25% enduring/maladaptive response at 7 days, to remain constant over 30 days. As setting the affected individuals apart from the unaffected approximates clinical studies, it might also help to clarify some of the pending issues in PTSD research.