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Neurology Reviews.Com

Vol. 9, No. 8
August 2001


NEWS ROUNDUP:
NEW AND NOTEWORTHY INFORMATION

Allopurinol—a drug used for the treatment of gout—provides neurocardiac protection in infants with hypoplastic left heart syndrome who undergo heart surgery using deep hypothermic circulatory arrest, according a study in the July issue of Pediatrics. The randomized, placebo-controlled, blinded trial of 318 infants undergoing this reconstructive heart surgery found that there were significant benefits only for higher-risk infants, not for infants with lower risk, non-hypoplastic left heart syndrome. “We found that infants with hypoplastic left heart syndrome treated with allopurinol had significantly fewer seizures than those not treated, and significantly fewer cardiac events, such as acute reductions in heart and respiratory rate,” said lead author Robert R. Clancy, MD.

School-aged children, 7 to 8 years old, with a history of febrile convulsions, had better mnemonic capacity than age-matched control subjects. A study published in the July 10 Neurology administered four tasks to the children: learning, spatial memory retrieval, sequential memory retrieval, and delayed recognition. Children in the febrile-convulsive group out-performed controls in all but one working memory task. Onset of the convulsions before age 1 was the only risk factor for decreased mnemonic function.

The brains of prepubescent boys and girls (ages 8 to 11 years) process faces and expressions differently, according to a study in the July Neuropsychology. Seventeen boys and 18 girls were given face-recognition-memory tests and facial-affect-identification tests. The boys demonstrated greater right-hemisphere brain activity during the presentation of face stimuli. Also, boys’ right-hemisphere activity correlated with their accuracy in identifying facial affect—a relationship not demonstrated in girls. “The girls’ approach could be more of an advantage in detecting the fine changes in affective expression, and thus they would be better at reading people,” the study authors proposed.

A study in the July Stroke showed that elderly disabled stroke patients with serum 25-hydroxyvitamin D concentrations of less than or equal to 5 ng/mL have an increased risk of hip fracture. The study followed 236 stroke patients for 2 years; 88 were rated deficient, with 25-hydroxyvitamin D levels of 10 ng/mL or less; 76 were insufficient (10 to 20 ng/mL); and 72 were sufficient (at least 21 ng/mL). The combination of immobility and increased age may cause the deficiency that in turn reduces bone mineral density, which can increase fracture risk.

Spouses experience a decline in their sense of well-being and an increase in psychological stress within days of their mate’s stroke, according to a study in the July Stroke. Eighty-three spouses (mean age, 57 years) of first-time stroke patients were evaluated using the Psychological General Well-Being Index 10 days after the stroke. The extent of the disability of the stroke patient correlated with the spouse’s outlook of the future. There was no sex difference noted, as both husbands and wives showed similar reductions in emotional well-being.

CD4 and CD8 T cells can clear out mosquito-borne viruses from neurons located in the spinal cord and brain stem, but not from neurons in the cerebral cortex. Diane Griffin, MD, PhD, coauthor of the study that appears in the July 13 Science, stated, “This research shows that virus-infected neurons do not all respond to the lymphocyte immune system in the same way to clear infection. Therefore, different combinations of antibody and T-cell immunity may be needed for control of infection and recovery from encephalitis depending on the parts of the brain or spinal cord that are infected.”

Genetically engineering adult neurons to produce larger amounts of integrin affects nerve fiber growth, according to a study in the July 1 Journal of Neuroscience. The researchers used a modified adenovirus to insert extra copies of an integrin gene into sensory neurons of adult rats. A second group of neurons received copies of another gene. Increasing the amount of these integrin proteins increases the amount of nerve fiber growth in adult neurons to levels that are comparable with those in newborn animals.

Corticotropin-releasing hormone (CRH) exposure during infancy may be the culprit for certain types of impaired cognition and memory loss. CRH appears to kill cells in the hippocampus, leading to brain damage that was previously associated with adverse effects from adrenal steroid hormone exposure from stress during infancy. Rats injected with CRH were impaired in memory tests, as compared with those that did not receive CRH, and showed brain cell loss in the hippocampus. The cell death continued to progress and worsen with age, although there was only a single episode of CRH stress inducement at infancy. According to study results published in the July 10 Proceedings of the National Academy of Sciences, rats who were prevented from producing adrenal steroid hormones still lost memory function and cells. Further study is being conducted to determine which stresses cause increases in CRH in the brain and how CRH regulates cell function in the hippocampus.

Gene microarray was used in a recent study to profile the gene expression in several kinds of brain tumors—glioblastoma multiforme and anaplastic astrocytoma (high-grade gliomas), low-grade astrocytomas, and benign extra-axial brain tumors—in comparison with gene expression in normal brain tissue. According to the study in the July 15 Cancer Research, glioblastoma multiforme tumors over-expressed 14 known growth factor– related genes and structural/extracellular matrix–related genes. An a4 chain-containing laminin isoform, laminin-8, was expressed in blood vessel walls of glioblastoma multiforme tumors, and laminin-9 was expressed in the blood vessel walls of low-grade tumors and normal brain tissues. The researchers determined that glioblastoma multiforme tumors that demonstrated an over-expression of laminin-8 had a shorter mean time to tumor recurrence (4.3 months) than did those that over-expressed laminin-9 (9.7 months).

Abciximab, a platelet glycoprotein IIb/IIIa receptor inhibitor, in addition to aspirin and heparin does not increase stroke risk in patients undergoing percutaneous coronary intervention. A study published in the July 4 issue of JAMA analyzed data from four double-blind, placebo-controlled, randomized trials (EPIC, CAPTURE, EPILOG, and EPISTENT) conducted between November 1991 and October 1997. The researchers found that there was no significant difference in stroke rate between patients assigned abciximab and those assigned placebo. Patients receiving abciximab and standard-dose heparin had a higher hemorrhagic stroke rate than did those receiving abciximab and low-dose heparin (0.27% versus 0.04%, respectively).

A multicenter exploratory Phase 2A clinical study of the experimental immunotherapy for Alzheimer’s disease, AN-1792 (also known as AIP-0001) is slated to begin later this year. Approximately 375 patients with mild to moderate Alzheimer’s disease will be enrolled at various sites in the United States and Europe. The study, which is expected to take two years, will measure the immune response to beta amyloid peptide and assess the impact on cognitive, physiological, and biological markers of the disease, say the cosponsors, Elan Corporation and Wyeth-Ayerst Laboratories. Phase 1 safety studies indicate that the compound is well tolerated and may cause a sufficicent immunological response in some patients.

A new technique that enables the detection of disease-related prion protein (PrPSc) in variant Creutzfeldt-Jakob disease (vCJD) is described in the July 19 Lancet. The highly sensitive method allows for detection of PrPSc in peripheral tissues such as the tonsil, spleen, retina, and optic nerve. The researchers, from the Prion Disease Group at the Imperial College School of Medicine in London, hope the immunoblot method for detection of PrPSc in vCJD tissue will be used to provide an upper limit on PrPCs concentrations, including blood, to form risk-management models to prevent the spread of vCJD via biopsy and surgical instruments.

Electric shock or lightning may be the cause of some cases of motor neuron disease, according to research published in the July Journal of Neurology, Neurosurgery, and Psychiatry. The authors pointed to six cases referred to their clinic in France. Each patient had received an electric shock of up to 380 volts from either lightning or an electric cable. Motor neuron symptoms appeared 10 days to 33 months after the electric shock in five of the patients, and 18 years after the event in the sixth patient. In all patients, the disease began at the point of entry of the shock. Given the homogenous profile of the patients, the authors concluded that a link between electric shock and motor neuron disease is likely.

A team of researchers from Memorial Sloan-Kettering Cancer Center in New York City has developed a new mouse model of brain tumors. Two mouse models were generated; one strain of mice expressed excess growth factor in undifferentiated cells, and the second strain of mice expressed platelet-derived growth factor (PDGF) in differentiated astrocytes. Both strains of mice developed mostly low-grade gliomas. It seems that the timing of PDGF expression may play a crucial role in determining what characteristics a glioma displays. The authors of the August 1 Genes & Development article reported that excess PDGF expression in mature astrocytes may generate gliomas by “dedifferentiating” the astrocytes into glial progenitor-like cells. The researchers demonstrated that the severity of the gliomas in both strains of mice could be increased by the loss of an important cell cycle arrest gene, leading them to conclude that some low-grade gliomas are made up of proliferating glial progenitor cells that are somehow blocked in their ability to differentiate. That the low-grade gliomas consisted of undifferentiated glial-progenitor-like cells suggests that these types of tumors may respond well to drugs that promote glial cell differentiation.

NR

—Lyris Autran, Heidi W. Moore

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