Seventy-two hour infusion of NXY-059 was found to be ineffective for the treatment of ischemic stroke within six hours after the onset of symptoms, according to the results of a randomized, double-blind trial published in the August 9 New England Journal of Medicine. Investigators with the Stroke-Acute Ischemic NXY Treatment (SAINT) II trial reported that the distribution of scores on the modified Rankin scale did not differ between the NXY-059–treated acute ischemic stroke patients (n = 1,588) and those who received placebo (n = 1,607). In addition, the odds ratio for trichotomization into modified Rankin scale scores of 0 to 1 versus 2 to 3 versus 4 to 6 was 0.92, confirming the lack of benefit. Scores on neurologic and activities of daily living scales also showed no evidence of efficacy of NXY-059.

he inverse dose-dependent association between cigarette smoking and Parkinson’s disease was stronger in current compared with former smokers, reported researchers in the July Archives of Neurology. The pooled analysis of eight US case-control studies (2,328 cases with Parkinson’s disease and 4,113 controls matched by age, sex, and ethnicity) and three cohort studies (488 cases and 4,880 controls selected from age- and sex-matched risk sets) indicated no influence on disease risk with regard to sex or level of education. The inverse trend held true for all age-groups except for the very elderly (those older than 75), said the researchers. They recommended further study of age at diagnosis and ethnicity, as Hispanic and African-American patients did not show the reduced risk observed in white and Asian patients. Chewing tobacco and smoking cigars and/or pipes also appeared to have an inverse effect in males, noted the authors.

The FDA has approved a 200-mg dose of Stalevo® (levodopa with carbidopa and entacapone) for the treatment of patients with Parkinson’s disease symptoms. This higher dose (the drug was previously available only in strengths of 50, 100, and 150 mg) may reduce the number of tablets a patient needs to take for symptom relief and provides clinicians with flexibility in treating patients experiencing symptom reemergence due to end-of-dose “wearing off.” A bioequivalence study determined that two tablets of 100 mg levodopa/25 mg carbidopa taken concomitantly with 200 mg entacapone was safe and thus implicated safety for the new strength of Stalevo. The most common adverse events associated with the drug were dopaminergic in nature (eg, dyskinesia, nausea).

High rates of caffeine consump-tion may reduce cognitive decline in women older than 65 with dementia, according to a study in the August 7 Neurology. In a community-based sample of 4,197 women, those who reported drinking more than three cups of coffee or the equivalent in tea per day showed less four-year decline in verbal retrieval (odds ratio [OR], 0.67) and visuospatial memory (OR, 0.82) than did those who reported drinking one cup. The protective effect also increased with age (ORs, 0.73 and 0.3 for those ages 65 to 74 and those 80 or older, respectively). No relation was found between caffeine intake and cognitive decline in 2,820 men. Caffeine consumption did not reduce dementia risk; however, the researchers suggested that further studies may ascertain whether caffeine could be used to prolong the period of mild cognitive impairment in women prior to dementia diagnosis.

Statin withdrawal for three days after hospital admission was associated with a 4.66-fold increased risk of death or dependency at 90 days poststroke, reported researchers in the August 28 Neurology. Sixty percent of the 46 previously chronically statin-treated patients randomized to withdrawal were dependent (defined as having a modified Rankin Scale score greater than 2) at the end of follow-up—significantly more than those immediately given atorvastatin 20 mg/day (39% of 43 patients). Early neurologic deterioration and infarct volume were also significantly more frequent in the withdrawal group, reported the authors. In addition, compared with patients not previously treated with statins, patients who were treated and withdrew had a 19.01-fold increased risk of early neurologic deterioration and a 43.51-mL increase in mean infarct volume. The authors recommended that statin treatment be continued in the acute phase of ischemic stroke.

Interviews with 91 nondemented subjects indicated that exposure to prolonged stress plus having the e4 variant of apolipoprotein E (APOE e4) leads to memory decline, reported researchers in the September 1 Biological Psychiatry. Mean age of the participants was 78.8. Better scores on delayed recall of stories, word lists, and visual designs were seen in subjects with low stress versus those with high stress, as determined by salivary cortisol levels; APOE e4–negative subjects also obtained better scores on immediate and delayed recall of visual designs than did APOE e4–positive subjects. “Significant stress by APOE e4 interaction effects on memory and cortisol resulted from consistently worse memory and higher cortisol concentrations in the high stress, e4-positive group,” stated the researchers. Further studies will assess whether stress and APOE e4 interact to increase the risk of Alzheimer’s disease, they said.

Heavy alcohol use may increase the risk for stroke, according to the results of a prospective cohort study of Chinese men that was published in the online August 20 Annals of Neurology. At baseline, all 64,338 participants were 40 or older and were free of stroke; after more than 493,351 person-years of follow-up, 3,434 incident strokes occurred, with 1,848 stroke deaths. The investigators reported the following adjusted relative risks (RRs) for incident stroke in drinkers compared with nondrinkers: 0.93 for participants consuming one to six drinks per week; 1.02, seven to 20 drinks per week; 1.22, 21 to 34 drinks per week; and 1.22, three or more drinks per week. Corresponding adjusted RRs for stroke mortality were 0.93, 0.98, 1.15, and 1.30, respectively. The authors recommended that heavy drinking be targeted in strategies for the prevention of stroke.

Women with probable visual migraine with aura may have a 1.5-times greater risk of ischemic stroke than women without migraines, as reported in the August 9 online Stroke. Data from a population-based case-control study of 386 women ages 15 to 49 with first ischemic stroke and 614 age- and ethnicity-matched controls indicated the greatest risk among migraineurs with aura with no history of hypertension, diabetes, or myocardial infarction—all medical conditions associated with stroke—compared with women with no migraine. In addition, the researchers reported sevenfold higher odds of stroke among women with probable migraine with visual aura who were current cigarette smokers and current users of oral contraceptives, compared with those who were nonsmokers and did not use oral contraceptives; a 6.9-fold increased odds was also observed in women with migraine with visual aura onset within the past year.

Two studies published in the August 16 Neuron illuminate how fragile X tremor/ataxia syndrome arises from a dysfunction on the FMR1 gene, the same gene that causes fragile X syndrome. In one study, researchers used a Drosophila model of the disease (complete with the hallmark FMR1 alleles with repeating CGG sequences) to show that the protein Pur alpha interacts with the repeats, implicating it in the disease pathogenesis. They posited that overexpression of Pur alpha “could suppress rCGG-mediated neurodegeneration in a dose-dependent manner.” The researchers in the second study investigated the RNA-binding proteins hnRNP A2/B1 and CUGBP1 in a transgenic Drosophila model. They reported that the two proteins interact, while hnRNP A2/B1 interacts directly with the RNA repeats; however, overexpression of the proteins was found to suppress the phenotype.

A genomewide association analysis identified many new candidate genes, including FLJ10986, for susceptibility to sporadic amyotrophic lateral sclerosis (ALS), as reported in the August 23 New England Journal of Medicine. Ten genetic loci were significantly associated with sporadic ALS in a discovery series and two replication series. Forty-one additional loci had significant associations in two out of three series, said the researchers. The most significant association with sporadic ALS was found for a single nucleotide polymorphism near the uncharacterized FLJ10986 gene (odds ratio for genotype in patients vs controls, 1.35). “The FLJ10986 protein was found … in the spinal cord and cerebrospinal fluid of patients and of controls,” noted the study authors. Other specific polymorphisms seemed to be associated with sex, age at onset, and site of onset of sporadic ALS, and warrant further investigation for their potential role in conferring susceptibility to the disease, the research team concluded.            

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