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Wednesday, March 05, 2014
By Olga Rukovets
Although men and women do share many of the same high-risk predictors for stroke — such as smoking, family history, and physical inactivity — some risk factors are either exclusive to women or affect women disproportionately. With this in mind, the American Heart Association/American Stroke Association convened a panel of experts in neurology, obstetrics, cardiology, epidemiology, and internal medicine to review and assess the literature on stroke risk in adults through May 15, 2013. They published the first gender-specific guidelines for stroke prevention in women — which were endorsed by the AAN, the American Association of Neurological Surgeons, and the Congress of Neurological Surgeons — in the Feb. 6 online edition of Stroke.
“This endeavor is important because women differ from men in a multitude of ways, including genetic differences in immunity, coagulation, hormonal factors, reproductive factors including pregnancy and childbirth, and social factors, all of which can influence risk for stroke and impact stroke outcomes,” the guideline authors wrote.
Overall, our extensive review of the evidence pointed to more gaps in knowledge than definitive recommendations, the lead author Cheryl Bushnell, MD, an associate professor of neurology, and director of the Wake Forest Baptist Stroke Center in Winston-Salem, NC, told Neurology Today. The primary message from the guidelines “is that many of the unique risk factors for women are present at younger ages (due to oral contraceptive use, pregnancy complications), so recognition of stroke risk and prevention strategies could start early to keep women from having a preventable stroke,” she said.
The most important recommendation from our review, Dr. Bushnell said, “is that women with a history of hypertension or preeclampsia during pregnancy are at risk for stroke and hypertension later in life.” Before this guideline, some providers and few women knew about this risk, she explained, and “the evidence for this relationship is pretty solid, as multiple meta-analyses have come to the same conclusion.” For this reason, the guidelines recommend documenting hypertension in women during pregnancy, preeclampsia/eclampsia, or gestational diabetes as risk factors for stroke in the medical record, “and beginning strategies to decrease their future risk of stroke at early ages, even as early as during their childbearing years.”
“We suggest considering treating blood pressure in the moderate range (150-159 mmHg systolic) for pregnant women, although there has to be careful consideration of maternal and fetal risk and benefit in this group” because of medication side effects. Predicting which women may go on to develop severe hypertension during pregnancy (>160/110 mmHg), she added, might also help identify which women should be treated.
The guidelines also make a strong recommendation for treating women at high risk of preeclampsia with low-dose aspirin or calcium supplements. “The implication is that if you can prevent preeclampsia, perhaps you have reduced the future risk of stroke by at least one notch,” said Dr. Bushnell.
The guidelines may be useful for neurologists who are counseling female patients with migraine with aura on how to reduce their overall stroke risk by focusing on some of the factors unique to or more common in women. Many migraine medications may also lower blood pressure, she said, thus, reducing stroke risk and “killing two birds with one stone.”
The authors recommended the development of a female-specific risk score to reflect stroke risk across the lifespan. This would help clinicians “determine a woman’s long term-risk in the future, and be used as a guide to developing early prevention strategies and determine how early they should start,” said Dr. Bushnell. Potentially, these differences in risk score may point to gender-specific dosing or pharmacological approaches, “but there is a huge gap in research in this area,” she said, adding that recognizing these risk factors is the first step.
Dr. Bushnell noted that further research is also needed to determine if these gender-specific risk factors are independently related to future stroke risk when traditional risk factors, such as cholesterol and hypertension, are included in the score. Studies are needed, she said, to determine which women with hypertension during pregnancy or preeclampsia will be at highest risk for stroke later in life, as well as among “diverse populations, since African Americans, in particular, are at risk for hypertension during pregnancy.”
Stay tuned for the full discussion of the guidelines and their implications in the March 20 issue of Neurology Today. Read up on emerging research in stroke here: http://bit.ly/1e1svle.
Tuesday, March 04, 2014
BY TOM VALEO
Citalopram (Celexa), one of the most widely used antidepressants, quells the agitation commonly found in Alzheimer’s patients, but a dosage of 30 mg per day can disrupt normal heart rhythms and cause slight cognitive decline, according to a paper published in the Feb. 19 issue of the Journal of the American Medical Association (JAMA).
The Citalopram for Agitation in Alzheimer Disease Study (CitAD) randomized 186 patients with probable Alzheimer’s disease (AD) and agitation into two groups. Ninety-four received citalopram for nine weeks, while 92 received a placebo. Both groups also received psychological counseling and other assistance. In addition to assessing the effect of citalopram on agitation, the study sought to measure the effects of the drug on patient functionality and caregiver distress, and to identify any safety concerns.
However, on Aug. 22, 2011 — about two-thirds of the way through the study — the Food and Drug Administration (FDA) issued an advisory stating that citalopram carried a dose-dependent risk of QT prolongation, which can cause palpitations and sudden death due to ventricular fibrillation. Prescribing information advises against a dose above 40 mg per day in adults, and over 20 mg per day in anyone 60 years or older.
In response, the researchers excluded recruits with QTc greater than 450 ms for men and greater than 475 ms for women, included an electrocardiogram at week three and after the first dose increase to 30 mg, and added serum magnesium to routine electrolyte monitoring.
Although patients taking citalopram showed a 40 percent reduction in agitation according to one measure, compared with 26 percent on placebo, the researchers observed changes in the electrical activity of the heart in the form of QTc prolongation in the citalopram group and, to their surprise, a modest worsening of cognitive function.
As a result they concluded that citalopram “cannot be generally recommended as an alternative treatment” at a dose of 30 mg per day.
“In most instances citalopram should be kept at 20 mg or lower in individuals who are 60 years of age and older,” said lead author Anton P. Porsteinsson, MD, William B. and Sheila Konar professor of psychiatry at the University of Rochester School of Medicine and Dentistry, and director of the University of Rochester Alzheimer's Disease Care, Research and Education Program. “The FDA recommendations are accurate.”
While the study showed robust effects at a dose of 30 mg per day, Dr. Porsteinsson suspects 20 mg per day would also be beneficial, “but in our study we just didn’t have enough participants at lower doses to say anything about efficacy,” he said.
He advised physicians who prescribe a dose above 20 mg per day to take into account the potential for QT prolongation. For patients with a normal QTc, the risk of heart irregularities “is probably not a big deal,” at least if the patient is checked before and after taking citalopram, Dr. Porsteinsson said. “For myself, I would certainly consider citalopram one of the first-line agents, but I would start someone at 10 mg and take them to 20 mg, and then keep them at that dose, and only in very rare circumstances push above that dose,” he added.
The cognitive impact of citalopram was much more of a surprise to the researchers. Patients taking citalopram showed a one-point drop on the Mini-Mental State Examination (MMSE), while those taking a placebo improved somewhat after nine weeks.
“We did not expect that, and we don’t quite know what to make of it,” Dr. Porsteinsson said. “One possibility is that we are just seeing a drift toward the mean as there were baseline differences on the MMSE score between the two groups.”
“You could say that a 1.4 decline on the MMSE is a minimally significant change,” he said. “But again, it’s something to keep in mind, and if you have a patient who has more of a cognitive change, you would need to consider the possibility that it’s related to the medication.”
For continued discussion with the study authors and outside commentators, stay tuned for the March 20 issue of Neurology Today. Read more about research on Alzheimer’s disease here: http://bit.ly/Kl13rc.
Monday, March 03, 2014
Theodore Leon Munsat, MD
August 6, 1930 – November 22, 2013
Chairman Emeritus, Department of Neurology, Tufts Medical Center
President, American Academy of Neurology 1989-1991
Former Chairman of World Federation of Neurology ALS Research Group
The memorial ceremony for Dr. Theodore (Ted) Munsat will be held in the Sackler Auditorium, 145 Harrison Avenue, First Floor, Tufts Medical Center, at 2 pm on Saturday, April 5, 2014. The ceremony will be followed by a reception at the same location.
Those who are planning to attend should RSVP by Friday, March 14 to Dr. Walter Bradley at firstname.lastname@example.org.
Read Neurology Today's tribute to Dr. Munsat's life and work: http://bit.ly/1iJyfqs.
Friday, February 28, 2014
BY OLGA RUKOVETS
For the field of sports neurology, Jeffrey Kutcher, MD, brought home an exciting victory from the 2014 Winter Olympic Games in Sochi. Although Dr. Kutcher was not there to compete, his presence in Sochi as the first full-time sports neurologist for Team USA was a game-changer.
In an e-mail interview with Neurology Today, Dr. Kutcher, director of the Michigan Neurosport Program, associate professor of neurology at the University of Michigan School of Medicine, and team physician with the Michigan Athletic Department, offers a behind-the-scenes look at being a staff neurologist for the Olympic Games.
WHAT DID YOU (OR THE OTHER DOCTORS) ENCOUNTER NEUROLOGICALLY? WERE ANY PARTICULAR EVENTS MORE PRONE TO INJURY THAN OTHERS?
First, I need to emphasize that I was just one part of a world-class team of clinical providers brought over by the United States Olympic Committee (USOC). Every day, we interacted with the medical staff from other countries, providing support and receiving support as needed. In addition, there were on-site emergency personnel provided by the host country. Together, the medical community on the mountain worked together for the health and safety of all athletes, regardless of country.
It was truly an amazing experience to work in that environment — something that I will never forget. We saw concussions, of course, in addition to a wide spectrum of trauma. There was a very typical injury rate at these games, across all of the different events, despite what you may have heard in the media. As far as which events are more prone to injury, I need only say that I spent a lot of time at the extreme park.
WHAT WERE THE MEDICAL FACILITIES IN SOCHI LIKE FOR ASSESSING AND TREATING ATHLETES?
Absolutely incredible, really. We had a clinic in the mountain village 50 steps from my front door, with onsite x-ray, CT, and MRI; procedure rooms; and local specialists. We could even get same day optometry exams and glasses made next day. For more significant trauma, we had several options nearby that were easily accessible by ambulance or helicopter.
DID YOU ENCOUNTER ANY PRESSURE FROM ATHLETES TO RESUME COMPETITION POST-INJURY?
None. Naturally, there is disappointment and no shortage of tears when you tell an athlete their Olympic Games are over. The incredible amount of time, dedication, sacrifice, and pain that it takes to get there all comes to a quick and dramatic conclusion. In the end, however, you see an incredible amount of respect for brain injury and gratitude that somebody was there to look out for them.
COMING BACK FROM SOCHI, WHAT TIPS WOULD YOU HAVE FOR OTHER NEUROLOGISTS WHO MAY BE WORKING WITH ATHLETES, SPORTS TEAMS?
Make sure you’re in it for the right reasons. Remember that you have an ethical obligation to work for your patient and your patient alone.
Do not get caught up in the outcome or the environment. You absolutely cannot be a fan. Not everybody can do this and stay objective, so do some serious introspection before you put yourself in a situation that might compromise your patient’s health.
Of course, you need to be very comfortable making decisions and sticking with them. Finally, respect the unique nature of the sports you work with. Work to understand the game itself and the athlete’s motivation for playing. It will make you a better clinician.
Read the extended interview in an upcoming issue of Neurology Today. Also, see the first report from Dr. Kutcher on his journey to the Olympic Games: http://bit.ly/MkaaZX.
Thursday, February 27, 2014
BY RICHARD ROBINSON
A novel combination of cutting-edge gene discovery techniques has turned up 18 new genes for hereditary spastic paraplegia (HSP), including genes for cellular processes not previously implicated in the disease. The study, published in the Jan. 31 issue of Science, also highlighted potential links between HSP and other neurodegenerative diseases that may be targeted therapeutically.
The study began with 55 consanguineous families displaying an autosomal recessive form of the disease. Consanguinity increased the likelihood of finding disease-causing recessive mutations. Recessive mutations were required for this study because of what happened next. DNA from individuals with the disease was first analyzed with whole-exome sequencing, determining the sequencing of every coding region in the genome. For most genes, the sequences of the two alleles, one inherited from each parent, were different. These could be ruled out as the source of the disease, because a recessive disease requires two identical copies of the gene, explained lead author Joseph Gleeson, MD, professor of neurosciences and pediatrics at the University of California, San Diego.
That left a much smaller number of homozygous genes, many of which could be eliminated based on the absence of any unusual sequence variation within them, compared with the population at large. Genes were further ruled out if the variant did not segregate with the disease.
This method turned up 13 known HSP genes, and identified 15 candidate genes not previously associated with HSP. These were examined further, first by screening for them in 200 HSP patients without a previous genetic diagnosis; five of the 15 genes were confirmed in this group.
The 18 new genes bring the total number of HSP genes to 70, which largely cluster into a much smaller number of pathogenic categories. Besides ER-associated degradation and membrane traffic control, these include lipid and myelin biosynthetic pathways, as well as axonal guidance and synapse-related genes. A new category implicated in this study is nucleotide metabolism, with three new genes identified encoding enzymes that metabolize purines. How mutations in these genes cause HSP is unknown.
Finally, Dr. Gleeson asked about commonalities among the HSP network and those of other neurologic diseases, including neurodegenerative, developmental, and seizure disorders. “We found that the set of HSP seeds plus candidates significantly overlaps with sets of genes previously implicated in three neurodegenerative disorders: amyotrophic lateral sclerosis, Alzheimer’s disease, and Parkinson’s disease,” but not with the other types of disorders.
This gene discovery approach can’t be used for every disease, Dr. Gleeson noted. “Our work benefited in part because this condition is so genetically heterogeneous, but is still tractable.” Dr. Gleeson is currently applying this approach to other neurodevelopmental disorders.
Look for the full-text discussion of this research from study authors and commentators in the March 6 issue of Neurology Today. See our previous coverage of hereditary spastic paraplegia: http://bit.ly/1kcHhx5 and whole-exome sequencing: http://bit.ly/1pysDRH.