Investigators have developed a simple test to identify people with asymptomatic carotid stenosis who have an increased risk of stroke, as reported in the August 17 online Neurology. “Two potential markers of high risk are echolucent plaque morphology on carotid ultrasound and embolic signals in the ipsilateral middle cerebral artery on transcranial Doppler ultrasound (TCD),” the authors wrote. To explore the predictive value of a composite score based on these two measures, the investigators recruited 435 participants with asymptomatic carotid stenosis and collected baseline ultrasound images and TCD data. “Plaque morphology assessed using a simple, and clinically applicable, visual rating scale predicts ipsilateral stroke risk in asymptomatic carotid stenosis,” the authors wrote. They also noted that the combination of both markers allows a greater prediction than either measure alone.

Researchers have identified a possible common cause of several forms of amyotrophic lateral sclerosis (ALS), according to a study published in the August 21 online Nature. Although some genetic mutations have been shown to cause certain forms of the disease, the causes of certain types of familial ALS and of the vast majority of sporadic ALS had been unknown. “Here, we show that mutations in the UBQLN2, which encodes the ubiquitin-like protein ubiquilin 2, cause dominantly inherited, chromosome-X-linked ALS, and ALS/dementia,” the investigators reported. They also performed functional analysis that showed that these mutations lead to impairment in protein degradation. “Therefore, our findings link abnormalities in ubiquilin 2 to defects in the protein degradation pathway, abnormal protein aggregation, and neurodegeneration, indicating a common pathogenic mechanism that can be exploited for therapeutic intervention,” the authors concluded.

Using computational approaches and drug and genomic information, scientists can predict new uses for existing medicines, according to two studies published online in the August 17 Science Translational Medicine. The practice, known as drug repositioning, was investigated in a study supported by the NIH. The researchers used a computer program that searched through possible drug-disease combinations (from a set of 164 established drug compounds and 100 diseases) to identify drug and disease combinations whose gene expression patterns essentially canceled each other out. In one specific case, topiramate, an anticonvulsant for the treatment of epilepsy, was found to be a potential therapeutic option for inflammatory bowel disease. “The application of established drug compounds to new therapeutic indications … offers several advantages over traditional drug development, including reduced development costs and shorter paths to approval,” the authors wrote. “This computational method provides a systematic approach for repositioning established drugs to treat a wide range of human diseases.”

Women with depression may have an increased risk of subsequent stroke, according to the results of a study published in the August 11 Stroke. A group of researchers followed-up more than 80,000 women (age range, 54 to 79) without a history of stroke from the Nurses’ Health Study to determine if depression was associated with stroke. Depressive symptoms were assessed at multiple time points, and antidepressant medication use and physician-diagnosed depression were recorded biennially. “During six years of follow-up, 1,033 incident strokes were documented,” the authors reported. “For each cycle, participants who reported current depression had an increased risk of stroke (hazard ratio, 1.41), whereas individuals who only had a history of depression were at nonsignificantly elevated risk (hazard ratio, 1.23), compared with women who never reported a diagnosis of depression or antidepressant medication use.”

According to a study published in the August 11 online JAMA, women with sleep-disordered breathing were more likely to develop dementia or cognitive impairment, compared with women without the disorder. “Sleep-disordered breathing (characterized by recurrent arousals from sleep and intermittent hypoxemia) is common among older adults,” the authors wrote. “However, it remains unclear whether sleep-disordered breathing precedes cognitive impairment in older adults.” To investigate this association and its potential mechanisms, the researchers conducted a prospective sleep and cognition study of 298 women without dementia who underwent polysomnography. “Compared with the 193 women without sleep-disordered breathing, the 105 women (35.2%) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (31.1% versus 44.8%),” they reported. “Measures of sleep fragmentation (arousal index and wake after sleep onset) or sleep duration (total sleep time) were not associated with risk of cognitive impairment.”

Older patients (ages 80 to 91) with Alzheimer’s disease experience less severe cognitive or brain changes than younger patients (ages 60 to 75) with the disease, according to a study published in the August 10 online Neurology. Researchers compared hippocampal volume and cortical gray matter thickness of 105 patients with Alzheimer’s disease and 125 healthy controls to determine if brain morphometric and cognitive profiles differed according to age. “Several cognitive domains (executive function, immediate memory, and attention/processing speed) were less abnormal in the very old with Alzheimer’s disease than in the young old with Alzheimer’s disease,” the investigators wrote. “Similarly, the very old with Alzheimer’s disease showed less severe cortical thinning than the young old with Alzheimer’s disease.” The authors noted that mild cases of Alzheimer’s disease in older people might go undetected due to these age-related differences in cognitive and morphometric changes.

Researchers have found new genetic variants associated with multiple sclerosis (MS), as reported in the August 10 Nature. “In a collaborative genome-wide association study involving 9,772 cases of European descent … we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci,” the authors wrote. One-third of the genes they identified have previously been implicated in other autoimmune diseases, suggesting that the same general processes occur in more than one type of autoimmune disease; two of the genes were also involved in the metabolism of vitamin D, supporting the existence of a link between genetic and environmental risk factors. “Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of MS,” the investigators concluded.

The US Food and Drug Administration (FDA) has approved Botox (onabotulinumtoxinA) for injection for the treatment of urinary incontinence caused by detrusor overactivity in adults with neurologic conditions, including multiple sclerosis (MS) and spinal cord injury. The FDA’s approval was based on two phase III clinical trials in which onabotulinumtoxinA was administered to 691 patients with MS or spinal cord injury and urinary incontinence; when the drug was injected directly into the bladder muscle, episodes of urinary incontinence were significantly reduced. Researchers at Allergan, Inc (Irvine, California) believe the drug will benefit people who cannot tolerate an oral anticholinergic medication.

Patients with Parkinson’s disease who visit a neurologist are less likely to be placed in a nursing home, have a lower risk of hip fracture, and have a lower likelihood of death than those who do not receive care from a neurologist, according to a study published online in the August 10 online Neurology. Only 58% of patients visited a neurologist, and race and sex were significant demographic predictors for receiving treatment. “Women and minorities with Parkinson’s disease obtain specialist care less often than white men,” the researchers stated. “Neurologist care of patients with Parkinson’s disease may be associated with improved selected clinical outcomes and greater survival.”

A survey of graduating neurology residents reveals that 94% feel comfortable using t-PA, compared with 73% in a survey from 2000. The results of the survey were published online in the August 4 Stroke. The researchers sent a 12-item survey to neurology residents about their experience and confidence with assessment of patients with acute stroke and treatment with t-PA. Of 491 residents, 281 (58%) responded, with 95% reporting that they had personally administered t-PA and 98% reporting that they had been involved in post–t-PA care. “Neurology residents’ experience and comfort treating acute ischemic stroke with t-PA increased significantly between 2000 and 2010,” the authors concluded, “as did resident exposure to stroke teams and formal training in the NIH Stroke Scale.”

Hypertension, diabetes, smoking, and obesity during midlife are associated with an increased rate of progression of vascular brain injury, hippocampal atrophy, and decline in executive function later in life, researchers reported in the August 2 Neurology. “Our aim was to test the association of vascular risk factor exposure in midlife with progression of MRI markers of brain aging and measures of cognitive decline,” the investigators wrote. More than 1,300 people without dementia (mean age, 54) were enrolled in the study. After ten years, the researchers recorded changes in participants’ regional and total brain volume, memory recall, and performance on executive functioning tests. Hypertension and obesity in midlife were most greatly associated with diminished executive function; diabetes and smoking were associated with a more rapid increase in atrophy and decrease in brain volume. “Longitudinal changes in brain structure were significantly correlated with decline in memory and executive function,” the authors concluded.

Statins may lower the risk for future stroke in young adults who have already had an ischemic stroke, according to research published in the August 2 Neurology. Researchers investigated the effects of these cholesterol-lowering drugs in 215 patients (mean age, 39.1) who had an ischemic stroke of unknown etiology and categorized them into three groups based on statin use (never used, continuous use, or discontinuous use). “Seventy-two patients (33%) used a statin at some time during follow-up,” the researchers reported. “Twenty-nine (20%) events occurred among the 143 patients never on a statin, none among the 36 with continuous statin, and 4 (1%) among the 36 with discontinuous statin.” The risk of a second event was 77% lower for patients who had used a statin after first stroke.

Researchers believe they have found a better approach to diagnosing temporal lobe epilepsy (TLE) using 7-Tesla MRI, according to a study in the July 11 online Radiology. The investigators performed 7-Tesla MRI on eight patients with TLE and 11 healthy controls. “All eight patients with TLE had hippocampal abnormalities on the epileptogenic side,” the researchers stated. “Hippocampal malrotation was observed in three patients with TLE and four control subjects.” Subsequent subregional analysis revealed that six patients with TLE had selective lateral Ammon horn atrophy, and one patient had diffuse Ammon horn and dentate gyrus atrophy. The authors concluded: “Ultrahigh-field-strength MRI permitted detection of selectively greater Ammon horn atrophy in patients with TLE and hippocampal sclerosis.”

—Ariel Jones

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