Higher diastolic blood pressure (DBP) is cross-sectionally and independently associated with cognitive impairment, investigators reported in the August 25 Neurology. The association was found after adjusting for economic factors, depressive symptoms, and current use of any antihyperintensive medication in 30,228 black and white men and women (45 and older). “An increment of 10 mm Hg in DBP was associated with a 7% higher odds of cognitive impairment,” the researchers stated. “No independent association was identified between impaired cognitive status and systolic blood pressure (odds ratio [OR], 1.02) or pulse pressure (OR, 0.99).” No evidence of nonlinear relationships between any blood pressure components and impaired cognitive status was found.

Use of smokeless tobacco products is associated with risk of fatal myocardial infarction and stroke, according to the August 18 online BMJ. Investigators from Sweden and the United States conducted a meta-analysis of 11 observational studies (primarily including men). “Eight risk estimates were available for fatal myocardial infarction: the relative risk for ever use of smokeless tobacco products was 1.13 and the excess risk was restricted to current users,” the investigators stated. “The relative risk of fatal stroke, on the basis of five risk estimates, was 1.40.” Increased risk of fatal myocardial infarction was shown in studies from both geographic locations. “Data on dose-response were limited but did not suggest a strong relation between risk of dying from either disease and frequency or duration of use of smokeless tobacco products,” the researchers noted.

A mutation in transcriptional repressor hDEC2-P385R is associated with a human short sleep phenotype, according to a study in the August 14 issue of Science. Investigators found that within a small extended family, two members with the mutation had lifelong shorter daily sleep requirements than most persons. The researchers then genetically engineered mice and fruit flies to express the mutated human gene and studied its impact on behavior and sleep patterns. “Activity profiles and sleep recordings of transgenic mice carrying this mutation showed increased vigilance time and less sleep time than control mice in a zeitgeber time- and sleep deprivation-dependent manner,” the study authors stated. “These mice represent a model of human sleep homeostasis that provides an opportunity to probe the effect of sleep on human physical and mental health.”

The FDA has approved Extavia for reducing the frequency of clinical exacerbations in patients with relapsing forms of multiple sclerosis (MS). It is also indicated in patients who have had a first clinical episode of MS and have features consistent with the disease as shown by MRI. Extavia is a new branded version of interferon beta-1b and the same medicinal product as Betaseron. Interferon beta-1b has been shown to reduce annualized relapse rates by 34%, with patients nearly twice as likely to remain relapse-free for more than two years, compared with those receiving placebo. Injection site necrosis has been reported in 4% of patients in controlled trials, and anaphylaxis has been reported as a rare complication of interferon use. Extavia is marketed by the Pharmaceuticals Division of Novartis (East Hanover, NJ) and is expected to be available this fall.

White matter hyperintensity (WMH) is more strongly related to amnestic mild cognitive impairment (aMCI), and infarcts are more strongly related to nonamnestic MCI, according to a study in the August 11 issue of Neurology. Researchers investigated the relationship of WMH volume and infarcts in brain per MRI to MCI in 679 elderly persons without dementia. WMH was adjusted for total cranial volume, and MCI was defined using the Peterson criteria. WMH was more strongly related to aMCI (OR, 1.9) than nonamnestic MCI (OR, 1.6). However, infarcts were more strongly related to nonamnestic MCI (OR, 2.7) than aMCI (OR, 1.4). “In secondary analyses using continuous cognitive scores as outcomes, WMH, but not infarcts, were related to memory, while infarcts were more strongly related with nonamnestic domains,” the researchers noted. “The nature of WMH in aMCI requires further study,” they concluded.

Intellectually normal children with seizures had neuropsychologic deficits at seizure onset, per a study published in the August 18 issue of Neurology. Investigators compared 282 children between ages 6 and 14 who had an IQ of 70 or higher and with a first recognized seizure to 147 healthy siblings. “In this intellectually normal cohort, 27% with just one seizure and up to 40% of those with risk factors exhibited neuropsychologic deficits at or near onset,” the researchers stated. Risk factors included multiple seizures (ie, second unprovoked seizure, odds ratio [OR], 1.96), use of antiepileptic drugs (OR, 2.27), symptomatic/cryptogenic etiology (OR, 2.15), and epileptiform activity on the initial EEG (OR, 1.96). Increased odds for neuropsychologic impairment were associated with absence epilepsy (OR, 2.00).

The H5N1 avian influenza virus may increase the risk for Parkinson’s disease and other neurologic disorders, according to a report in the August 10 online Proceedings of the National Academy of Sciences. In a mouse model, investigators showed that the virus travels from the peripheral nervous system into the CNS to higher levels of the neuroaxis. “In regions infected by H5N1 virus, we observe activation of microglia and alpha-synuclein phosphorylation and aggregation that persists long after resolution of the infection,” the researchers stated. A significant loss in dopaminergic neurons in the substantia nigra pars compacta was also observed, 60 days after infection. “Our results suggest that a pandemic H5N1 pathogen, or other neurotropic influenza virus, could initiate CNS disorders of protein aggregation including Parkinson’s and Alzheimer’s diseases,” the investigators concluded.

The FDA has approved Sabril (vigabatrin) tablets and oral solution for two difficult-to-treat epilepsies. Vigabatrin is indicated as monotherapy for pediatric patients ages 1 month to 2 years with infantile spasms for whom the potential benefits outweigh the potential risk of vision loss, and as adjunctive add-on therapy in adults with refractory complex partial seizures who have not responded to alternative treatments, and for whom the potential benefits outweigh the risk of vision loss. Vigabatrin use has been linked to permanent bilateral concentric visual field constriction in 30% or more of patients that ranges in severity from mild to severe. Vigabatrin is manufactured by Lundbeck, Inc (Deerfield, Illinois).

Compared with women without epilepsy, epileptic seizures during pregnancy increased the risk for low-birth-weight infants, preterm delivery, and small for gestational age by 1.36-fold, 1.63-fold, and 1.37-fold, respectively, according to a study in the August Archives of Neurology. Researchers in Taiwan matched 1,016 women with epilepsy with single births from 2001 to 2003 and who had been diagnosed with epilepsy in the two years prior to index delivery with 8,128 women without chronic disease. The authors then compared women with epilepsy who had seizures during pregnancy to women with epilepsy who did not have seizures and found that the risk of infants being small for gestational age increased most significantly (odds ratio, 1.34) among those who had seizures during pregnancy.

P2X7 receptor antagonist, Brilliant blue G (BBG), reduced spinal cord anatomic damage and improved motor recovery in rats without evident toxicity when administered 15 minutes after injury, researchers reported in the July 28 Proceedings of the National Academy of Sciences. Treatment with BBG, a derivative of a commonly used food color (FD&C blue No. 1) that is used to give M&Ms and Gatorade their blue tint, also directly reduced local activation of astrocytes and microglia, in addition to neutrophil infiltration. “These observations suggest that BBG not only protected spinal cord neurons from purinergic excitotoxicity, but also reduced local inflammatory responses,” investigators stated. “Systemic administration of BBG may thus comprise a readily feasible approach by which to treat spinal cord injury in humans.”

Although angiotensin-converting enzyme (ACE) inhibitors as a class do not appear to be associated with dementia risk or cognitive decline in older, hypertensive (HTN) adults, within-class differences may occur regarding these outcomes, suggests a study in the July 13 Archives of Internal Medicine. Investigators identified 158 cases of dementia among 414 participants who were exposed to ACE inhibitors and 640 who were not. There was no association between exposure to all ACE inhibitors and risk of dementia (hazard ratio [HR], 1.01). “However, centrally active ACE inhibitors were associated with 65% less decline in Modified Mini-Mental State Examination scores per year of exposure, and noncentrally active ACE inhibitors were associated with a greater risk of incident dementia (adjusted HR, 1.20) and greater odds of disability in instrumental activities of daily living (adjusted OR, 1.16), compared with other anti-hypertension drugs,” investigators reported.

Researchers have found an association between the cytochrome P450 (CYP) 2C19*2 variant and diminished platelet response to clopidogrel treatment and poor cardiovascular outcomes, according to a study in the August 26 JAMA. Clopidogrel was administered for seven days to 429 healthy Amish persons. “Thirteen single-nucleotide polymorphisms on chromosome 10q24 within the CYP2C18-CYP2C19-CYP2C9-CYP2C8 cluster were associated with diminished clopidogrel response, with a high degree of statistical significance,” noted the study authors. “The relation between CYP2C19*2 genotype and platelet aggregation was replicated in clopidogrel-treated patients undergoing coronary intervention.” In addition, those with the variant were more likely (20.9% vs 10.0%) to have a cardiovascular ischemic event or death in one year of follow-up.

Intramuscular AVI-4658 induces the expression of dystrophin, benefiting patients with Duchenne muscular dystrophy, according to a study in the August 26 online Lancet Neurology. Investigators assessed the safety of AVI-4658.Two patients received 0.09 mg AVI-4658 in 900 µl (0.9%) saline, and five received 0.9 mg AVI-4658 in 900 µl saline. “In randomly chosen sections of treated EDB muscles, the mean intensity of dystrophin staining ranged from 22% to 32% of the mean intensity of dystrophin in healthy control muscles (mean, 26.4%), and the mean intensity was 17% (range, 11% to 21%) greater than the intensity in the contralateral saline-treated muscle,” the researchers stated. “In the dystrophin-positive fibers, the intensity of dystrophin staining was up to 42% of that in healthy muscle.”

—Laura Sassano

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