Taking antiplatelets, angiotensin-converting enzyme (ACE) inhibitors, and statins to prevent stroke may result in additive reduction in stroke severity, as reported in the April 25 Neurology. Researchers analyzed data from 210 consecutive patients presenting within 24 hours of stroke onset. Results showed that 69 patients were not taking antiplatelets, ACE inhibitors, or statins at stroke onset; 47 were taking antiplatelets alone; 43 were taking either antiplatelets and statins or antiplatelets and ACE inhibitors; and 20 were on the triple-combination therapy. A higher percentage of patients on triple therapy had shorter length of hospitalization and better functional status at discharge compared with those on single or dual therapy. In addition, patients on triple therapy had a lower baseline NIH Stroke Scale score than did patients on dual therapy, antiplatelets alone, or no prestroke therapy.

The appearance of parenchymal enhancement of stroke lesions and the hyperintense middle cerebral artery sign on MRI may help identify stroke patients at risk of hemorrhage in the skull, according to findings presented at the 106th Annual Meeting of the American Roentgen Ray Society. Researchers analyzed the MRI results of 24 patients with ischemic stroke within five hours of symptom onset. Ten patients developed hemorrhaging within the skull; six of these patients had the parenchymal enhancement, and five had the hypertensive middle cerebral artery sign. Neither parenchymal enhancement nor hypertensive middle cerebral artery sign was found in the 14 patients who did not develop hemorrhaging.

The American Heart Association/American Stroke Association Stroke Council has released primary prevention guidelines for stroke, published May 4 in the online Stroke. The guidelines listed age, gender, low birth weight, race/ethnicity, and genetic factors as nonmodifiable risk factors, while well-documented and modifiable risk factors included hypertension, cigarette smoke exposure, diabetes, atrial fibrillation and certain other cardiac conditions, dyslipidemia, carotid artery stenosis, sickle cell disease, postmenopausal hormone therapy, poor diet, physical inactivity, and obesity and body fat distribution. Less well-documented or potentially modifiable risk factors included metabolic syndrome, alcohol abuse, drug abuse, oral contraceptive use, sleep-disordered breathing, migraine headache, hyperhomocysteinemia, elevated lipoprotein(a), elevated lipoprotein-associated phospholipase, hypercoagulability, inflammation, and infection.

A smaller hippocampus is associated with an increased risk for conversion from mild cognitive impairment to Alzheimer’s disease, as reported in the May Archives of Neurology. Twenty participants with mild cognitive impairment were followed clinically and neuropsychologically for three years. Six patients developed Alzheimer’s disease, seven remained stable, and seven improved. Patients with Alzheimer’s disease had 9% smaller left and 13% smaller right mean hippocampal volumes compared with patients who remained stable, as well as significantly smaller hippocampi (left, 24%; right, 27%) compared with patients who improved. Volumetric analyses showed 16% hippocampal volume loss in patients who remained stable relative to those whose mild cognitive impairment improved.

Patients who have a strong reaction to Epstein-Barr virus may be at risk for multiple sclerosis, as indicated by findings reported in the June Brain. Researchers studied 20 untreated Epstein-Barr virus–seropositive patients with multiple sclerosis and 20 healthy carriers of Epstein-Barr virus. Peptide-specific CD4+ memory T cells in patients with multiple sclerosis showed increased proliferative capacity and an enhanced interferon-γ production, according to the investigators. T-cell responses to Epstein-Barr virus–encoded nuclear antigen I differed between patients and controls, while T-cell responses to three other latent and three other lytic immunodominant Epstein-Barr virus antigens and human cytomegalovirus epitopes did not.

Researchers have found a novel pathologic hallmark of amyotrophic lateral sclerosis at the molecular level, according to two studies published in the May 2 Proceedings of the National Academy of Sciences. In one study, researchers used mouse models to show a molecular mechanism by which the mutated superoxide dismutase protein is "converted to aggregated and apparently amyotrophic lateral sclerosis–associated toxic dimers and multimers by redox processes." In the second study, researchers observed evidence for incorrect disulfide cross-linking of the immature, misfolded mutant proteins leading to insoluble aggregates. These aggregates were specific to the spinal cord, whereas brain and liver tissue had no aggregates, the investigators found.

Extended-release oxybutynin impairs memory by a magnitude equivalent to 10 years of brain aging, according to findings presented at the 101st Annual Meeting of the American Urological Association. Healthy participants 60 and older were randomized to receive the M3-selective muscarinic receptor antagonist darifenacin, extended-release oxybutynin, or placebo for three weeks. At 30 minutes from initial presentation, delayed recall of name–face associations, first name–last name associations, and object locations were assessed. Darifenacin had no significant negative effect on the recall of name–face associations at week 3, while extended-release oxybutynin did. Darifenacin treatment also did not affect other parameters, unlike extended-release oxybutynin, which had significant negative effects on performance on other memory tests at various time points.

Ceftriaxone treatment may help prevent dementia in patients with HIV, according to findings presented at the 58th Annual Meeting of the American Academy of Neurology. Researchers grew human neuronal cell cultures, treated them with ceftriaxone, and exposed them to two proteins implicated in the development of HIV dementia: Tat and gp120. Results showed that ceftriaxone protected neurons against both proteins, and the dose needed for protection was well within the range currently used for treatment of bacterial infections, stated the researchers. Although ceftriaxone is approved by the FDA, the investigators said that more data are needed to support use of the drug in patients with HIV dementia.

Researchers have found a novel strategy and a highly effective new cell type for repairing central nervous system injuries, as reported in the April 27 online Journal of Biology. Robust axon growth and restoration of locomotor function after acute transection injuries of an adult rat spinal cord were promoted by transplantation of astrocytes from embryonic glial-restricted precursors. Growth of more than 60% of ascending dorsal column axons into the lesion centers was promoted by transplantation of glial-restricted precursor–derived astrocytes into dorsal column injuries. A total of 66% of these ascending dorsal column axons extended beyond injury sites. "Predifferentiation of glial precursors into glial-restricted precursor–derived astrocytes before transplantation into spinal cord injuries leads to significantly improved outcomes over precursor cell transplantation," concluded the researchers.

The agonist l-AP-4 could protect nigral dopaminergic neurons from the selective toxicity of rotenone in patients with Parkinson’s disease, according to the April 19 Journal of Neuroscience. Using cell cultures, researchers found that l-AP-4 activated group III metabotropic glutamate receptors and was capable of inducing "a rapid and transient activation of the microtubule-associated protein kinase extracellular signal-regulated kinase." In addition, l-AP-4 significantly attenuated rotenone- or colchicine-induced microtubule depolymerization and decreased colchicine toxicity on tyrosine hydroxylase–positive neurons, both in a microtubule-associated protein kinase kinase–dependent manner. The investigators also found that paclitaxel occluded the protective effect of l-AP-4 against rotenone toxicity. "These findings may offer a novel neuroprotective approach against rotenone-induced parkinsonism," concluded the investigators.

Researchers have identified a protein that regulates amyloid-α peptide activity, as reported in the April 27 Nature. The investigators performed a search for presenilin-interacting proteins that differentially affected γ- and ε-site cleavage events and found that TMP21 was a component of presenilin complexes and differentially regulated γ-secretase cleavage without affecting ε-secretase activity. The researchers noted that if the binding of peptides to the luminal N terminus or to the cytosolic C terminus of TMP21 regulates the effect of TMP21 on γ-site cleavage, "these ligands, or molecular mimics of TMP21 itself, might provide a way to manipulate g-site cleavage (and thus amyloid-α production in patients with Alzheimer’s disease) therapeutically."

NR