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Neurology News

Follow our Neurology News blog for the latest news on neurologic diseases and research.

Tuesday, January 22, 2019


Patients hospitalized with epilepsy or seizures were frequently readmitted to the hospital at 30 days, most commonly for epilepsy or convulsion, according to a retrospective cohort study published online on December 21 in Neurology.

While those readmitted were more likely to have multiple medical comorbidities, inpatient adverse events, such as epilepsy, also increased the odds of readmission.

On a national level, little is known about the risk factors for readmission of seizure patients or the burden of readmission in this population, researcher Leah Blank, MD, MPH, of the University of Pennsylvania in Philadelphia and her colleagues reported.

Currently, the Medicare program is no longer providing payment for inpatient care delivered within 30 days after an initial admission for a series of diagnoses, including heart attack.

"The list is likely to expand, and epilepsy would be a reasonable first neurologic disease to include, given its multiple treatment choices, and the clear association between outpatient epilepsy care quality and health outcomes across epilepsy subtypes," the researchers wrote.

They emphasized this is important because the 30-day readmission metric is increasingly being used to assess hospital performance.

In the study, the team analyzed data on emergently hospitalized adults with a primary discharge diagnosis of seizure or epilepsy from the Healthcare Cost and Utilization Project's 2014 Nationwide Readmissions Database (NRD), which allows for the identification of 29 preexisting chronic medical conditions. In addition, the NRD allows researchers to calculate an Elixhauser comorbidity score—a comprehensive set of 30 comorbidity measures for use with large administrative inpatient datasets—categorized as 0-1, 2, 3, and 4-plus comorbid conditions.

Elective hospitalizations, hospitalizations in which the patient left against medical advice, or hospitalizations that occurred near the end of the year due to insufficient follow-up were excluded.

A total of 139,800 hospitalizations met the inclusion criteria for 30-day readmission.

Approximately 10.8 percent (15,094 patients) were readmitted within 30 days; epilepsy or convulsions (17 percent) and sepsis (7 percent) were the most common primary reasons for readmission.

"Importantly, the most common reason for readmission was epilepsy/convulsion. This suggests that there is an opportunity for improvement as patients are not being readmitted for unforeseeable complications," the researchers wrote.

They suggest the findings warrant further investigation with more "granular, patient level data to better understand the health care structure and processes associated with the presence of adverse events."

The relationship between outpatient follow-up and readmission was not assessed due to the lack of availability on outpatient data.

The researchers noted other study limitations included administration claims data, which contains codes produced for billing and documentation purposes, that prevented them from tracking admissions one year to the next due to inadequate follow-up.

The Mirowski Family Fund and by the American Epilepsy Society/Epilepsy Foundation Research and Training Fellowship for Clinicians and a Neurologic Clinical Epidemiology Training Grant supported the study.

The researchers reported no conflicts of interest.


Blank LJ, Crispo JAG, Thibault DP, et al. Readmission after seizure discharge in a nationally representative sample. Neurology 2018; Epub 2018 Dec 21.

Wednesday, January 16, 2019


Preeclampsia and other hypertensive disorders of pregnancy (HPD) have been associated with increased rates of long-term cardiovascular risk, including stroke. Aspirin use during pregnancy is known to reduce the incidence of preeclampsia and is typically discontinued after giving birth. Now, an observational study, published online on December 26 in Neurology, suggests aspirin use for primary prevention may lower stroke risk in women with prior HDP.

The study authors found women with preeclampsia and related disorders who did not take aspirin regularly had a 1.5-fold higher risk of stroke before age 60, compared to women without a history of HDP.

Stroke risk did not increase for women with preeclampsia who did use aspirin, compared to women who did not have hypertensive disorders.

The researchers, led by Eliza C. Miller, MD, Columbia University Mailman School of Public Health, New York City, commented in Neurology that guidelines for estimating 10-year cardiovascular risk to inform primary prevention with aspirin do factor in preeclampsia despite the fact that the condition "is identified as a sex-specific risk factor for stroke by the American Heart Association/American Stroke Association."

In the study, the team analyzed data from 83,749 women enrolled in the California Teachers Study who were 60 years or younger (average age 53) during 1995 to 1996 and followed for validated stroke outcomes through 2015. Using a self-administered questionnaire, women answered whether they had a prior stroke; those with no stroke were included in the analysis. Out of 83,749 women, 4,070 (4.9 percent) had a history of preeclampsia, either self-reported in an early questionnaire (n=3,361), hospital-diagnosed (n=972), or both (n=262).

During an average follow-up of 18.1 years, a total of 123 admissions for stroke were reported in the preeclampsia group (3.0 percent, event rate 166 per 100,000 woman-years) compared with 1,823 (2.3 percent, 127 per 100,000 woman-years) in the non-preeclampsia group (p=0.002). Stroke risk was higher in women with preeclampsia history, even after adjusting for age, race/ethnicity, tobacco use, migraine, hypertension, obesity, and diabetes mellitus (adjusted HR 1.3, 95% CI 1.2–1.4). But, this group showed no increased risk for stroke before age 60 (adjusted HR 1.2, 95% CI 0.9–1.7).An interaction between aspirin use and a history of HDP on stroke risk was seen before age 60. Women with preeclampsia who regularly took aspirin had a lower stroke risk before age 60, compared to those who did not take aspirin (adjusted HR 0.8, 95% CI 0.4-1.7 vs adjusted HR 1.5, 95% CI 1.0-2.1, p=0.18). Among women who took aspirin, no increased risk of hemorrhagic stroke was reported. No interaction was found between statin use and history of HDP for all stroke risk (p=0.69).

The researchers noted aspirin mitigated stroke risk before age 60, but not overall stroke, in women with a history of HDP.

The study authors contend that HDP should be considered as an important risk factor for future stroke, and that women who have had the condition in pregnancy may benefit from primary prevention with aspirin, even if they don't have additional vascular risk factors.

They findings warrant further research to "better understand the mechanisms by which preeclampsia and related disorders increase stroke risk, and randomized controlled trials may be warranted to establish the efficacy of aspirin for the primary prevention of stroke in selected women with a history of HDP," the study authors wrote.

Study limitations included the small number of strokes that occurred in both groups to the study sample being predominantly white and likely to have delayed childbearing to a later age than women in the general California population.

Dr. Miller reported support from the National Institute of Neurological Disorders and Stroke, the StrokeNet Training Core, and the National Center for Advancing Translational Science.

The other study authors disclosed relationships with BMS-Pfizer Alliance for Eliquis, Merck/Organon, and Auxilium.


Miller EC, Boehme AK, Ching NT, et al. Aspirin reduces long-term stroke risk in women with prior hypertensive disorders of pregnancy. Neurology 2018; Epub 2018 Dec 26.

Tuesday, January 15, 2019


A commonly-used anti-diabetic medication, pioglitazone, reduced neuropathic pain induced by the chemotherapeutic medication cisplatin in a sample of mice, according to a study published in the November 29 issue of Pain.

The hope is that pioglitazone could one day be used simultaneously with the chemotherapeutic agent to mitigate the progressive, irreversible, and painful peripheral neuropathy that has been a side effect of cisplatin, according to the study author author Donald Simone, PhD, professor in the department of diagnostic and biological sciences at the School of Dentistry at the University of Minnesota, and his colleagues,

Cisplatin, one of the first generation of platinum drugs, has been in use for the last 50 years for the treatment of advanced and metastatic cancers. Platinum-based compounds lead to DNA cross linkage ultimately preventing mitosis, thus suppressing tumor growth.

"The major conclusion of the paper is that administration of pioglitazone, or drugs like it that activate peroxisome proliferator-activated receptor (PPAR) gamma, may eliminate cisplatin-evoked pain by protecting peripheral neurons against oxidative stress," he told Neurology Today in an interview. "And we think [the reduction of oxidative stress is] really important in the reduction of neuropathy and pain."

The reactive oxygen species (ROS) of the dorsal root ganglion (DRG) are generated during normal oxidative metabolism, and their levels are held in check by enzymes that detoxify ROS [for example, superoxide dismutase (SOD) and catalase] as well as low molecular weight antioxidants, The authors explained that chemotherapy treatment through inactivation of SOD and catalase leads to the accumulation of ROS, resulting in oxidative stress.

Dr. Simone and colleagues administered cisplatin to the mice at a dose of 1 mg/kg on a daily basis, and discovered there was significant mechanical and cold hyperalgesia after the third or fourth injection (p >0.001) 24 hours after the third injection of cisplatin.

Co-administration of pioglitazone blocked the development of cold sensitivity (p=0.005). A single dose of pioglitazone (10 mg/kg) after seven days of cisplatin treatment acutely reduced cisplatin-evoked pain in the mice by attenuating oxidative stress through activation of PPAR gamma. This resulted in increased expression of oxidative stress defense enzymes. In addition, the authors demonstrated that the increase in enzymes occurred within small DRG neurons, which are responsible for transmission of painful stimuli.

To discover the mechanism underlying this blockage, Dr. Simone and colleagues also isolated the mouse RNA from the dorsal root ganglia (DRG) neurons and measured the effects of oxidative stress by cisplatin. They found that cisplatin contributed to oxidative stress in the DRG neurons by binding to nuclear and mitochondrial DNA, thus altering the expression of proteins required to maintain normal cellular function.

The study data also confirmed that pioglitazone rescued mitochondria from cisplatin-induced damage in DRG neurons."Our results are consistent with reports that pioglitazone rescues mitochondria

from cisplatin-induced oxidative stress by increasing mitochondrial biogenesis and expression of proteins for mitochondrial oxidative phosphorylation," the authors wrote.

Dr. Simone said that he would like to replicate the research in human subjects as a logical next step. "Both cisplatin and pioglitazone are approved by the US Food and Drug Administration, so it shouldn't be difficult to try this in a small sample of people," he said.

The study was funded by the National Institutes of Health and the study authors reported no disclosures.


Khasabova IA, Khasabov SG, Olson JK, et al. Pioglitazone, a PPARγ agonist, reduces cisplatin-evoked neuropathic pain by protecting against oxidative stress. Pain 2018; Epub 2018 Nov 29. 

Friday, January 11, 2019


Six months of regular aerobic exercise helped older adults with mild cognitive impairment (MCI) with no dementia and at risk for cardiovascular disease (CVD) improve their executive functioning, but not memory or language/verbal fluency, according to a randomized clinical trial published online on December 19 in Neurology.

Moreover, a combination of both aerobic exercise and the DASH (Dietary Approaches to Stop Hypertension) diet led to the largest improvement compared to controls.

"The DASH factor was not related to improved neurocognition, although we noted that greater benefits were observed among those participants who engaged in both exercise and the DASH eating plan compared to controls," principal investigator James A. Blumenthal, PhD, JP Gibbons Professor of Psychiatry at Duke University Medical Center in Durham, NC, and his colleagues wrote.

The ENLIGHTEN (Exercise and Nutritional Interventions for Cognitive and Cardiovascular Health Enhancement) trial aimed to investigate whether older adults with MCI but not dementia and cardiovascular disease risk factors (CVD) could improve executive functioning, memory, and verbal fluency by adding regular aerobic exercise, and/or the DASH diet.

The team enrolled 160 sedentary participants at the Duke Aging Center and the Duke Alzheimer's Disease Research Center between December 2011 and March 2016. The average age of the participants was 65 years; 66 percent were women; and were evenly divided between whites and minorities.

The researchers randomly assigned 41 participants to aerobic exercise alone, 41 to DASH alone, and 40 to a combination of aerobic exercise and DASH. Thirty-eight participants served as controls and only received health education via weekly 30-minute phone calls about health-related topics for three months and then biweekly for three months.

The aerobic exercise intervention consisted of 10 minutes of warm-up exercises followed by 35 minutes of continuous walking or stationary cycling three times a week for six months at 70 to 85 percent of their initial peak heart rate reserve for three months under supervision. Participants recorded their workouts in a weekly exercise log.

In the DASH diet intervention, participants received education and feedback on adherence by a nutritionist in a series of half-hour sessions by a nutritionist conducted weekly for the initial 12 weeks and then biweekly for weeks 13 to 24.

At six months, the researchers assessed neurocognition, dietary consumption, cardiorespiratory fitness, and cardiovascular disease risk (CVD) factors. Those who regularly engaged in aerobic exercise showed significant improvements (p = .046) in executive function. Compared to the exercise groups, the DASH diet groups experienced no significant changes in executive functioning (p = .059).

Among those who exercised, improvements in aerobic fitness (VO2 peak; p < .049) and reduced CVD risk (, p < .042) were also linked to improvements in executive function.

Greater improvements in treadmill duration (p < .001), 6-minute walk distance (p < .001), and daily steps (p < .001) were also seen.

Participants in both interventions saw the largest improvements in executive functioning (p = 0.012).

CVD risk factors decreased for those on the DASH diet, including total cholesterol, reduced weight and LDL lipoprotein, and a reduction in the number of hypertensive medications taken. Insulin improvements were seen in the exercise alone and the exercise and DASH diet groups.

Although the DASH diet was not associated with significant improvements in executive function, those in the aerobic exercise arm of the exercise and DASH group did reap benefits in executive function. Moreover, a reduction in sodium intake was also associated with improved executive function. Changes in potassium, magnesium, and calcium were not related to executive function.

The researchers believe "because there is considerable overlap in risk factors for CVD and dementia, strategies designed to reduce CVD risk also may be effective in improving neurocognition and reducing the risk of developing dementia."

 At least one CVD risk factor was present in study participants. For example, 21 had coronary heart disease and an additional seven had a history of transient ischemic attack without residual deficits.

The study author acknowledged that the trial was underpowered to detect differences between exercise and the DASH diet alone, which provides limited evidence on the relative benefits of these two interventions. In addition, the trial was only six months long; the researchers were unable to measure the long-term effects of exercise and diet on cognitive outcomes. Lastly, participants were highly motivated and did not drop out; these findings may not apply to less motivated groups.

A grant from the National Institutes of Health funded the study. The researchers reported no financial disclosures.


Blumenthal JA, Smith PJ, Mabe S, et al. Lifestyle and neurocognition in older adults with cognitive impairments: A randomized trial. Neurology 2018; 2018 Dec 19.

Wednesday, January 9, 2019


In a new study, investigators identified alcohol use and psychological distress among other risk factors for rapid eye movement sleep behavior disorder (RBD), in which patients violently act out their dreams. The disorder also has been associated with other neurodegenerative disorders, such as Parkinson disease (PD), dementia with Lewy bodies, or multiple system atrophy.

For their analysis, the team observed 30,097 people ages 45 to 85 (mean age 63) recruited between 2012 to 2015 from the Canadian Longitudinal Study on Aging (CLSA), a large, national, longitudinal study that collects information on the changing biological, medical, psychological, social, lifestyle and economic aspects of participants' lives. 

The researchers conducted in-person interviews with participants and screened them for a series of health conditions and asked about lifestyle, behavior, social, economic and psychological factors. Overall, the study's findings show male sex, low education, heavy drinking, smoking, antidepressant use, and measures of mental health are linked to RBD, but they do not prove a cause-and-effect relationship.

Published online in Neurology on December 26, the cross-sectional, nationwide Canadian study found that people with RBD were more likely to be moderate to heavy drinkers (18.9 percent versus 14.3 percent), current smokers (8.9 percent vs 6.4 percent), and past smokers (42.7 percent vs 36.9 percent) than those without the disorder.

Moreover, those with RBD used antidepressants more frequently (13.4 percent vs 6.2 percent), scored higher on the Kessler Psychological Distress Scale (15.2 ± 5.33 vs 13.9 ± 1.86) and were likely to report at least moderate psychological distress (10.9 percent vs 6.6 percent).

Patients also had a diagnosis of mental illness (34.9 percent vs 21.9 percent), with a higher incidence of physician-diagnosed anxiety (13.8 percent vs 7.3 percent) and depressive disorder (20.7 percent vs 13.9 percent).

They also had a higher rate of positive screening for post-traumatic stress disorder (10.5 percent vs 4.0 percent).

The study investigators, led by Chun Yao, MSc, of McGill University in Montreal, noted that there may be several explanations for the relationship between mental illness and risk for RBD. "One is that those with mental illness may tend to endorse multiple symptoms, including multiple sleep symptoms, as part of their illness. Another is that RBD itself can lead to psychosocial distress via disruption in sleep patterns or bed partner relations…," they wrote.

The cohort will continue to be observed to determine how many of these participants will go on to develop PD.

Study limitations included the reliance on self-reported data; differential misclassification, such as nonspecific sleep disturbance with depression, PTSD, apnea cases missed by screening questionnaires; and the lack of a diverse study sample—many participants were white, which may limit the generalizability of the findings to other ethnic groups.

The Canadian Institutes of Health Research and the Health Research Fund of Quebec supported the study.

The researchers reported relationships with Sunovion, Novartis, Sage Therapeutics, UCB, Eisai, the Centre de recherche de l'Universite de Montreal, the Multiple Sclerosis Society of Canada, Fonds de la Recherche en Sante, Parkinson Society of Canada, Weston-Garfield Foundation, Michael J. Fox Foundation, Webster Foundation, Biotie, Roche/Prothena, Teva Neurosciences, Biogen, Boehringer Ingelheim, Theranexus, and GE HealthCare.


Yao C, Fereshtehnejad SM, Keezer MR, et al. Risk factors for possible REM sleep behavior disorder: A CLSA population-based cohort study. Neurology 2018; Epub 2018 Dec 26.