The protein alpha-synuclein may play a role in the pathology of Parkinson's disease and Alzheimer's disease, according to a study in the May 1 Journal of Neuroscience. Researchers at the University of Pennsylvania Medical School, Philadelphia, reported that alpha-synuclein may interact with and regulate synaptic vesicles, thus influencing synaptic functions in the brain. After suppression of alpha-synuclein with antisense oligonucleotide technology, there was a significant reduction in the distal pool of synaptic vesicles.

Interictal and ictal electroencephalogram (EEG) monitoring can be used for a more accurate prediction of surgical outcome in mesial temporal lobe epilepsy, according to a report in the May Epilepsia. Surgical outcome was also favorably associated with regionalized or lateralized scalp EEG seizure patterns. The authors found that a combination of 100% unitemporal interictal epileptiform discharges (IEDs) and ictal EEGs lateralized to one temporal lobe was indicative of a good surgical outcome (88.9% of patients seizure-free). However, as asynchrony was observed in 25.0% of patients, the authors suggested that more than two seizures should be recorded for a diagnosis of epilepsy surgery in patients with mesial temporal lobe epilepsy and bitemporal IEDs.

The WRNp protein, associated with Werner's Syndrome, bonds with proteins Ku70 and Ku86, according to researchers from the National Institute on Aging. The Ku proteins stimulate WRNp protein to repair DNA breaks by trimming and degrading DNA ends. According to the report in the April 15 Genes and Development, the investigators will study the WRNp protein to explore why DNA repair becomes less efficient in Werner's syndrome and during normal human aging.

Cutaneous allodynia is associated with migraine, according to a study in the May Annals of Neurology. In 79% of the study population, cutaneous allodynia caused by thermal or mechanical stimulation of the head and forearms manifested during migraine. Participants reported no difference in pain thresholds outside migraine attacks. The authors hypothesized that the pathophysiology of migraine in allodynic patients involves central sensitization of second-order brainstem trigeminal neurons as well as peripheral sensitization of meningeal pain fibers.

A slower rate of rewarming may reduce cognitive decline after major heart surgery, according to researchers at Duke University Medical Center, Durham, North Carolina. During their study, 100 controls were rewarmed at the typical rate (0.56ºC/min) and 65 patients were rewarmed at a much slower rate (0.49ºC/min). Patients who were rewarmed slowly scored better on standard tests of cognition—particularly attention and concentration—six weeks after surgery, and diabetic patients scored twice as high as diabetic controls. The researchers suggested, during their presentation at the annual meeting of the Society of Cardiovascular Anesthesiologists, that the slower rewarming of the blood may help slow the increasing oxygen needs of the brain and organs.

The importance of cognitive screening will increase as the American population ages, suggested two studies in the May American Journal of Psychiatry. A Johns Hopkins University, Baltimore, study, which found that the mean length of stay after hospitalization was 10.4 days for patients with dementia and 6.5 days for patients without dementia, indicated that early detection of dementia could expedite treatment and reduce costs. A second multicenter study found that 61% of subjects with dementia revealed symptoms of other psychiatric illnesses upon screening.

Diagnostic criteria for new variant Creutzfeldt-Jakob disease were presented in the May Annals of Neurology. Data from 35 confirmed deaths due to new variant Creutzfeldt-Jakob disease indicated that the median duration of illness was 14 months and the median age at death was 29 years. In all cases, psychiatric symptoms such as depression, anxiety, and withdrawal were followed a median six months after onset by neurologic symptoms such as dysesthesia and paresthesia. In some cases, neurologic symptoms were not accompanied by neurologic signs, reported the researchers. Terminal stages of the disease were typically characterized by a progressive loss of function leading to akinetic mutism.

Biofeedback may help children reduce the number, intensity, and duration of migraine, suggested University of Kiel, Germany, researchers. According to their report in the March Applied Psychophysiology and Biofeedback, the ten children who learned to self-regulate their brains' slow cortical potential improved their migraine symptoms by up to 55%, while the children who did not learn biofeedback techniques experienced an up to 8% improvement. The researchers reported that the children's improvement may not have been entirely due to biofeedback, but that increased self-confidence in their ability to control migraine symptoms and a supportive family environment may have contributed to their improvement.

A new adeno-associated virus gene delivery system has been described in the May Nature Biotechnology and Nature Medicine. Larger genes such as those associated with the treatment of cystic fibrosis, hemophilia A, and certain types of muscular dystrophy are split and packaged into separate adeno-associated virus vectors. One vector contains the enhancer-promoter and a splice donor and the other contains a splice acceptor and the transgene. This two-vector approach may allow "development of gene therapy strategies that will carry exogenous DNA sequences with larger therapeutic cDNAs and/or regulatory elements," reported Stanford University, California, researchers.

Positron emission tomography (PET) in combination with APOE epsilon4 genotype and other genetic information can "assist in determining the time course for cerebral metabolic progression of Alzheimer's disease, provide homogenous subject groups for study in experimental therapy protocols, and offer an objective and noninvasive approach to presymptomatic metabolic trials," reported researchers in the May 23 Proceedings of the National Academy of Sciences. However, further investigation into the utility of PET or magnetic resonance imaging studies in the identification of early-affected Alzheimer's disease patients and the estimation of drug efficacy are warranted, cautioned Stanley I. Rappoport, MD, in an editorial commentary.

Diabetes has been reversed for more than a year for eight patients following islet transplantation by University of Alberta, Edmonton, researchers. Although each patient had needed 15 daily insulin injections, insulin production began almost immediately following transplantation. The procedure varied from typical islet transplantation: islets were taken from freshly donated organs, more cells were used (two organs were needed for each transplant), and the drug therapy was steroid-free. James Shapiro, MD, presented the study results at the first joint meeting of the American Society of Transplant Surgeons and the American Transplant Society.

The risk of dyskinesia in early Parkinson's disease may be reduced by management with ropinirole alone or with levodopa, if necessary, compared to management with levodopa alone, according to an article in the May 18 New England Journal of Medicine. At five years, the incidence of dyskinesia was 20% in the ropinirole group (regardless of levodopa supplementation) and 45% in the levodopa group. The mean daily doses at five years were 16.5 mg ropinirole (plus 427 mg levodopa in the supplementation group) or 753 mg levodopa.

A trial of the efficacy of linomide was terminated one month after full enrollment due to unanticipated serious cardiopulmonary toxicities, according to an article in the May 1 Neurology. It is not clear whether patients with multiple sclerosis may be more prone to linomide treatment-related adverse events than previously studied groups or whether linomide is a more toxic drug than had been suspected. In an accompanying editorial, Steven R. Schwid, MD, and John L. Trotter, MD, noted that authors, editors, and corporate sponsors are often reluctant to publish negative clinical trials. "Failure to report all meaningful trials leads to 'publication bias' in the literature, devalues the participation of patients and investigators, and ignores the many lessons such trials can teach," they concluded.

Herpes simplex virus 1 (HSV1) may play a role in the development of Alzheimer's disease suggested a University of California at Irvine, study. According to the report in the May Biochemistry, the "internal sequence of HSV1 glycoprotein B (gB) is homologous to the carboxyl-terminal region of the Aß peptide that accumulates in diffuse and neuritic placques in Alzheimer's disease." The viral protein was toxic to primary cortical neurons and formed thioflavin-positive fibrils in the study. The researchers noted that both genetic and environmental factors are involved in the etiology of Alzheimer's disease. Previously published studies suggested that although genetic loci confer a susceptibility to Alzheimer's disease, environmental factors such as head injuries, abnormal concentrations of metals (aluminum, zinc, or lead) in the brain, or infectious agents may modulate the onset and/or progression of the disease. "What's unique about our finding is that it points to a way in which herpes can be acting," said researcher Frank M. LaFerla, PhD.

The disruption of microcolumnar ensembles in the cerebral cortex may contribute to cognitive degeneration, suggested the authors of a study in the May 9 Proceedings of the National Academy of Science. Microcolumn loss and alteration were associated with Alzheimer's disease and Lewy body dementia, they said. Although microcolumn loss was directly associated with the development of neurofibrillary tangles, it was not strongly associated with amyloid ß plaque deposition. The authors suggested that the imaging technology could be useful in the analysis of schizophrenia and dyslexia, in which structural reorganization of the brain is assumed but is not apparent with conventional imaging techniques.

Sap from Croton trees may be a broad-acting analgesic agent, according to researchers at Albany Medical Center, New York, and Calgary University, Alberta. Ten pest control workers in Louisiana were randomized to a balm made from Croton tree sap or to placebo during a three-month, blinded trial. Within 90 seconds of application, the balm provided relief from fire ant, bee, and wasp stings, as well as from lacerations and plant reactions, reported the researchers. They believe that the sap from the Amazonian trees may also be of therapeutic benefit for pulmonary and inflammatory diseases.

—Kathryn Blair
Associate Editor

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