A clot-busting substance derived from vampire bat saliva may be used up to three times longer than the current stroke treatment window without increasing the risk for additional brain damage, according to a report in the January 9 rapid access issue of Stroke. The enzyme, Desmodus rotundus salivary plasminogen activator (DSPA), is more potent than the current US Food and Drug Administration-approved clot buster, recombinant tissue plasminogen activator (t-PA). When exposed to fibrin, the clot-busting activity of DSPA increases about 13,000-fold, compared with rt-PA, whose activity increases only 72-fold. In addition, researchers discovered that DSPA had no effect on two brain receptors that can promote brain damage, making it a safe treatment option for a longer period.

Inadequate rates of awareness and control of risk factors remain prevalent among African-American stroke patients, reported a study in the January 14 Neurology. Researchers assessed risk factors such as hypertension, diabetes, and high cholesterol in 1,086 patients enrolled in the African-American Antiplatelet Stroke Prevention Study. The investigators found that more than half of the patients with no reported history of hypertension actually had elevated blood pressure. Of the 60% of patients who reported no history of diabetes, 2% had an elevated serum glucose level, indicating a risk for diabetes. The investigators feel that they “must identify and address the underlying reasons why the African-American population appears to be less aware of and/or less likely to control the risk factors” contributing to stroke and heart disease.

Secular trends in cerebral infarct and coronary heart disease suggest a common etiology, but the different trends in cerebral hemorrhage show that its cause differs significantly from these conditions, researchers stated in the December 7, 2002, Lancet. Using data from autopsy studies, the researchers calculated the ratio of cerebral infarct to cerebral hemorrhage in the 20th century in England and Wales. Estimated cerebral infarct mortality and coronary heart disease mortality rose from 1932 to 1999, while death from cerebral hemorrhage showed a steady decrease. The investigators believe that these trends have important implications for disease prevention and also for studies of stroke epidemiology.

The INTERMED, a screening instrument used to assess multiple sclerosis case complexity, gives complementary information when compared with the Expanded Disability Status Scale (EDSS) and the Guy’s Neurological Disability Scale (GNDS), reported data in the January Journal of Neurology, Neurosurgery and Psychiatry. The needs of 100 newly referred patients diagnosed with multiple sclerosis were assessed and discussed in a multidisciplinary team; meanwhile, the patients underwent INTERMED, EDSS, and GNDS examinations. The researchers found that, compared with EDSS and GNDS, INTERMED showed the areas of the patient’s vulnerability and care needs, particularly in the psychological and social domains.

Pantothenate kinase 2 (PANK2) mutations are associated with all classic cases of Hallervorden-Spatz syndrome and one third of the cases of the atypical disease, researchers stated in the January 2 New England Journal of Medicine. Investigators classified 123 patients diagnosed with Hallervorden-Spatz syndrome on the basis of clinical assessment as having classic disease (early onset, rapid progression) or atypical disease (later onset, slow progression). Their DNA was sequenced for PANK2 mutations. The researchers found that all patients with classic disease had mutations, and among those with atypical disease, patients with the mutation were more likely to have speech and psychiatric problems. Researchers were most compelled by the “one-to-one correlation between the magnetic resonance imaging eye-of-the-tiger pattern and the presence of the PANK2 mutation, regardless of the severity of the disease.”

A genetic mutation underlying the 1C form of Charcot-Marie-Tooth disease was discovered by researchers at the University of Washington, according to a study in the January 14 Neurology. The researchers found mutations in the LITAF (lipopolysaccharide-induced tumor necrosis factor-alpha factor) gene. While the disease role of the mutated gene in the 1C form of Charcot-Marie-Tooth disease remains unknown, the researchers suggested that the mutated gene might be incapable of carrying out the protein degrading functions performed by the normal LITAF gene. The discovery could provide a molecular marker for the 1C form of Charcot-Marie-Tooth disease.

Agents that alter the blood levels of beta-amyloid protein in mouse models of Alzheimer’s disease represent a potential approach to treating the illness in humans, researchers reported in the January 1 issue of the Journal of Neuroscience. The investigators found that 13 mice bred to develop Alzheimer’s disease that had the beta-amyloid binding agents gelsolin or ganglioside GM1 injected into their peripheral bloodstreams had significantly less beta-amyloid protein than control mice. Use of gelsolin also resulted in a significant decrease in brain plaques. Karen Duff, PhD, co-author of the study, said the results were “proof-of-concept for a prophylactic approach” to treating Alzheimer’s disease. Other researchers viewed the results more cautiously, however, fearing that “this approach may trap a considerable amount of beta-amyloid in the cerebral blood vessels, weakening them and leading to cerebral hemorrhage.”

A new study by University of California, Davis, investigators is the first to conclusively link C-reactive proteins to the formation of blood clots. The study demonstrated that C-reactive proteins cause human aortic endothelial cells to produce higher levels of plasminogen activator inhibitor-1, an enzyme that inhibits clot breakdown, especially in patients with diabetes. “Based on these findings, if a patient has normal cholesterol but high levels of C-reactive protein, an aggressive course of treatment is recommended,” said Dr. Ishwarlal Jialal. “By relying on cholesterol alone, a physician could significantly underestimate a patient’s risk level [for heart attack, stroke, and other heart disease].” The study, published in the January 25 Circulation, also closely linked C-reactive protein and plasminogen activator inhibitor-1 to diabetes and metabolic syndrome.

Spasticity due to cerebral palsy, stroke, degenerative diseases, and head or spinal cord injuries may be more difficult to treat than was previously believed, according to research published in the February Muscle and Nerve. The study compared muscle fibers from healthy subjects to fibers from children with cerebral palsy. Researchers found that spastic muscle cells are shorter and stiffer than normal muscle cells. They develop passive tension at significantly shorter sarcomere lengths, and their elastic modulus (a measure of material stiffness) is greater. By addressing the issue of spasticity on a cellular level, the study challenged the theory and practice of surgery performed to lengthen spastic muscles and their tendons, suggesting such intervention might not relieve spasticity after all.

An international collaboration of scientists has identified a single gene, Six3, as a crucial factor in the normal development of the vertebrate forebrain, as published in the February 1 issue of Genes and Development. Transgenic mice deficient in Six3 died at birth and lacked the rostral forebrain and most anterior head structures, including the eyes and nose. The investigators determined that the protein encoded by Six3 blocks out a posteriorizing signal that sweeps through the putative forebrain during days 8.0 to 8.5 of mouse embryogenesis, thus securing the identity of anterior neural cells. The discovery also sheds light on a possible mechanistic basis for holoprosencephaly.

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