Read the most current news on neurologic diseases here! And we want your input. Leave your comments at the end of each article.
Thursday, October 23, 2014
by Rebecca Hiscott
Some patients who are in a vegetative state may retain fundamental brain networks that could support consciousness, according to a study published Oct. 16 in PLOS Computational Biology. By looking at the structure of brain networks associated with consciousness in vegetative patients, doctors may be able to identify those that still have some level of awareness, despite an inability to move or communicate, the authors wrote.
“Understanding how consciousness arises from the interactions between networks of brain regions is an elusive but fascinating scientific question,” Srivas Chennu, PhD, a researcher in the department of clinical neurosciences at the University of Cambridge, said in a news release. “But for patients diagnosed as vegetative and minimally conscious, and their families, this is far more than just an academic question. Our research could improve clinical assessment and help identify patients who might be covertly aware despite being uncommunicative.”
Using high-density electroencephalogram (EEG) measurements and graph theory, a mathematical modeling scheme, the researchers compared networks of neural activity in 32 vegetative and minimally conscious patients to those of 26 neurologically healthy adults.
They found that the complex brain networks that support consciousness are often severely impaired in patients in a vegetative state. As such, it appears that the brains of these patients can no longer support consciousness, they wrote.
Brain networks in two behaviorally similar vegetative patients (left and middle), but one of whom imagined playing tennis (middle panel), alongside a healthy adult (right panel). Image via Chennu et al. Spectral signatures of reorganized brain networks in disorders of consciousness. PLOS Comp Biol 2014: Epub 16 Oct 2014.
However, a 2006 study published in Science showed that some vegetative patients with severe brain injury remained aware of their surroundings. In that study, researchers asked the patients to imagine performing various tasks, such as playing a game of tennis. They then measured their brain activity in response to these prompts using functional magnetic resonance imaging. Activity was observed in the pre-motor cortex of some of the patients, suggesting some level of consciousness.
The researchers in the current study noted that patients who showed evidence of brain activity on the “tennis test” had better-preserved brain networks than other vegetative patients, and that those networks looked similar to those of healthy patients. “Hence, in such patients at least, we have found links between covert task-relevant attention and awareness, and the presence of brain networks that could support such advanced cognitive function despite the apparent lack of any consistent behavioral signs thereof,” they wrote.
Clinical assessment using EEG and the “tennis test” could potentially help identify vegetative state patients who retain some level of awareness, the authors wrote.
“If a patient’s ‘awareness’ networks are intact, then we know that they are likely to be aware of what is going on around them,” said Tristan Bekinschtein, PhD, a researcher with the MRC Cognition and Brain Sciences Unit and the Department of Psychology of the University of Cambridge. “But unfortunately, [the findings] also suggest that vegetative patients with severely impaired networks at rest are unlikely to show any signs of consciousness.”
For more coverage of coma and vegetative state research, browse our archives here: http://bit.ly/1wkXRys.
Wednesday, October 22, 2014
by Rebecca Hiscott
A new review of data from the US Food and Drug Administration (FDA) Adverse Event Reporting System database has found a strong link between the use of dopamine agonist drugs and the development of impulse control disorders (ICDs), including pathological gambling, hypersexuality, and compulsive shopping.
Image via Darren Johnson on Flickr.
The study, published in the Oct. 20 online issue of JAMA Neurology, confirms an association supported by previous research. The findings suggest that physicians should be vigilant in warning patients of possible side effects and monitoring for signs of ICDs in patients taking these drugs, the study authors wrote.
Dopamine receptor agonists are a common treatment for Parkinson’s disease; in the fourth quarter of 2012, US pharmacies dispensed 2.1 million outpatient prescriptions for the drugs. Dopamine agonists can also be prescribed for restless legs syndrome and hyperprolactinemia, a condition characterized by abnormally high levels of the hormone prolactin in the blood. While effective in treating Parkinson’s disease, the drugs have been linked in past research to side effects such as hallucinations, psychosis, excessive daytime sleepiness, and impulse control disorders – most notably pathological gambling, hypersexuality, and compulsive spending, but also binge eating, kleptomania, and poriomania, the impulsive need to wander away from home.
Past research suggests that ICDs may occur in 6 to 24 percent of patients treated with a dopamine agonist, the authors noted. Generally, the symptoms abate once the patient stops taking the medication.
Researchers from the US and Canada identified 1,580 cases of impulse disorders recorded between 2003 and 2012 in the FDA’s Adverse Event Reporting System, which collects data on incidences of adverse side effects to medication both in the US and internationally. Of those, 710 cases of ICDs, or 44.9 percent, were linked to the six FDA-approved dopamine agonist drugs marketed in the US, including 628 cases of pathological gambling, 465 cases of hypersexuality, and 202 cases of compulsive shopping.
Slightly more than half of the reported events occurred within the US. The drugs were prescribed for Parkinson’s disease in 438 cases (61.7 percent), restless legs syndrome in 169 cases (23.8 percent), and conditions associated with hyperprolactinemia in 25 cases (3.5 percent). Patients who developed ICDs from dopamine agonists had a median age of 55 years and 65.8 percent of them were male.
The number of reported instances of ICDs for all dopamine agonists increased from 26 in 2003 to 303 in 2012, but the proportion of ICD reports associated with dopamine agonists remained relatively stable during the 10-year period, the authors noted.
“At present, none of the dopamine receptor agonist drugs approved by the FDA have boxed warnings about the potential for the development of severe impulse control disorders as part of their prescribing information,” the authors wrote. “Our data, and data from prior studies, show the need for those prominent warnings. Physicians who prescribe dopamine agonists should also vigilantly monitor their patients, and ensure that patients, families, and caregivers are counseled about the risk of these serious adverse events.”
In an accompanying invited commentary, Howard D. Weiss, MD, an associate professor of neurology at Johns Hopkins Medical School, and Gregory M. Pontone, MD, an assistant professor of psychiatry at Johns Hopkins, stressed the need for neurologists to be vigilant in looking for signs of ICDs in their patients. “Some patients will be intentionally deceptive, dishonest, or lack insight, thereby concealing abnormal behaviors from their physicians and families,” they wrote.
“Before prescribing dopamine receptor agonist drugs, physicians should warn patients and their families or caregivers of the potential for triggering uncontrollable or excessive gambling, sexual interests, spending, or other behavioral addictions…Patients with a history of such disorders or a personal family history of such disorders or a personal or family history of obsessive-compulsive disorder, bipolar disorder, impulsive personality, alcoholism, drug abuse, or other addictive behaviors are at higher risk,” they added. “Dopamine receptor agonist drugs should be avoided in such patients.”
For more coverage of dopamine agonists in Parkinson’s disease, browse our archives here: http://bit.ly/1t9lxa4.
Tuesday, October 21, 2014
by Dan Hurley
First seen in California, then in Colorado, cases of acute flaccid myelitis marked by strikingly consistent MRI evidence of gray matter damage in the spinal cord are now believed to be affecting children in multiple states across the United States, according to neurologists tracking the outbreak. The reports have provoked grave concern among some specialists that the syndrome could affect even more patients next year.
To date, there are numerous unknowns surrounding this quickly evolving outbreak. Neurologists are not sure what causes it, but an emerging theory holds that it is likely linked to the summer’s nationwide outbreak of upper respiratory infections caused by enterovirus 68, even though the virus has not yet been isolated from any cerebrospinal fluid or central nervous system tissue studied in the past year.
No one is sure how long the symptoms will last, but some neurologists say that, so far, short-term recovery has been minimal to moderate. They said they know of no significantly beneficial therapy, but some believe that treatment with steroids may be unhelpful and perhaps even detrimental. Perhaps most tellingly, they do not yet agree on what to call the condition, or how to define it.
Some neurologists even question whether the cases seen so far represent a significant increase over background rates of prior years, given the paucity of earlier surveillance data.
The polio vaccine. Image via Wikimedia Commons.
The size of the current outbreak in the United States led the Centers for Disease Control and Prevention (CDC) to issue a request on Sept. 26 to all physicians to look for and report cases of what is being called acute flaccid myelitis, or “polio-like syndrome,” to their state health departments. By Oct. 15, the agency had already verified 37 cases in 16 states.
The CDC case definition used in its Sept. 26 announcement requires that a patient meet four criteria: the patient must be no older than 21 years of age and show an acute onset of focal limb weakness, with an MRI showing a spinal cord lesion largely restricted to gray matter. Cases must also have occurred on or after Aug. 1, 2014.
“Anecdotally, it does seem as if there are an unusually large number of these cases,” James J. Sejvar, MD, a neuroepidemiologist leading the CDC’s response to the outbreak, told Neurology Today. “We know there is a large outbreak of enterovirus 68 in children. We’ve also seen this cluster of polio-like syndrome in Colorado, and we’re hearing of additional reports of polio-like syndrome in other parts of the country. It’s premature to say at this point that the polio-like cases are caused by enterovirus 68, but certainly that’s one of our leading hypotheses.”
The only report definitively linking an infection with enterovirus 68 with a neurologic disorder came from New Hampshire in 2011, in which a case of fatal meningomyeloencephalitis occurred in a 5-year-old boy.
Although the CDC has not yet issued any recommendations or guidelines on treating the condition, Dr. Sejvar said, “We will indeed eventually come out with guidelines.”
IS THIS A NEW SYNDROME?
The California neurologists who used the term “polio-like syndrome” in a series of five cases reported at the 2014 AAN Annual Meeting published a report in the Morbidity and Mortality Weekly Report (MMWR) on Oct. 10, in which they called the condition “acute flaccid paralysis with anterior myelitis.” The paper identified 35 cases seen in California between June of 2012 and June of 2014. By the publication date, however, the terminology had already changed again.
“We’ve stopped using ‘anterior’ because not all the cases we’ve been seeing are anterior,” said Keith Van Haren, MD, a pediatric neurologist at Stanford University School of Medicine. “The term we are now using is acute flaccid myelitis.”
Just one week after the MMWR publication, he added, “We’ve seen several more cases that look just like it.” Nationally, he estimated, “If we’re talking about 50 states, I think the number of cases in the past few months is going to be in the neighborhood of 100 or more.”
While the numbers are far from clear at this point, most of the neurologists interviewed by Neurology Today said the cases are so remarkably distinct and unusual that they represent a sharp increase from whatever the background rate was previously.
IS IT A POLIO-LIKE SYNDROME?
“What we’re looking at is a disease indistinguishable in most respects from traditional polio, in terms of its symptoms,” Dr. Van Haren said. “Until now it was a really rare bird. Before 2012, we saw maybe one case every five years that wasn’t attributable to West Nile. Since 2012, we’ve seen many more cases. And since just this summer, we’ve seen even more.”
Jayne M. Ness, MD, PhD, an associate professor in the division of pediatric neurology at the University of Alabama at Birmingham, said that three cases have been seen at Children’s of Alabama since August, as well as one case earlier in the year.
“The three cases since August really look like each other. They have severe arm flaccidity and no mental status changes. All of them have similar spine MRIs showing gray matter involvement. You could lay all three MRIs on top of each other and they look almost the same. It’s pretty striking.”
In three of the four cases, the flaccidity was limited to one arm, reminding Dr. Ness of a peripheral nerve injury.
“They cannot move the arm at all,” she said. “It you lift the arm up, it literally drops. Sensation is usually intact. There might be slightly decreased sensation in the other arm, but these are younger kids, so they’re not always so cooperative in giving you a good sensory exam.”
In Kansas City, Jean-Baptiste Le Pichon, MD, PhD, a child neurologist at Children’s Mercy Hospital, said that three cases had been seen since August, plus a possible fourth case that was seen recently.
Dr. Le Pichon said that when cases of severe upper respiratory infections associated with enterovirus 68 were identified earlier this past summer in Kansas City, “I was thinking that we would see some type of neurologic pathology. I queried the Child Neurology Listserv for anyone having seen neurological complications associated with EV68, and sure enough, two weeks later we had our first case.
“It takes a day or two to make a diagnosis,” he said. “We have to eliminate transverse myelitis or Guillain-Barré. We need a good history and the MRI.”
The presentation, he said, is “virtually identical” to polio.
“The sudden onset of flaccid paralysis in single or multiple limbs with absolutely no sensory findings, the MRIs all showing uniformly a signal increase in the ventral horns of the spinal cord — this is exactly the same region of the spinal cord affected in polio,” Dr. Le Pichon said.
“Almost all of the patients have an increase in their white-blood cells in the cerebrospinal fluid. Some of the patients have brainstem findings and cranial-nerve findings. This is all the same as what polio does. None of us has ever seen anything like this before, with few exceptions.”
The largest cluster of cases is in Colorado. Teri L. Schreiner, MD, MPH, a pediatric neurologist at Children’s Hospital Colorado in Denver, said that she knows of 29 cases so far, including 12 since August.
“I would have a high degree of suspicion in any patient who has had a prior respiratory illness or cranial nerve dysfunction, who presents with flaccid weakness of one or more limbs,” said Dr. Schreiner. “In any patient who presents with those criteria, I would strongly encourage the provider to get an MRI of the brain as well as the spinal cord. We have also been performing nerve conduction studies, and are seeing evidence of acute denervation as soon as one or two weeks from onset of weakness.”
“We ran a report using similar ICD9 codes for the prior five years,” Dr. Schreiner said. “What we are seeing this year is many times greater. We are seeing a distinct outbreak with very stereotyped MRI findings and a clinical presentation that is atypical from anything else we have ever seen.”
Despite the comparisons to classic polio, the current outbreak of acute flaccid myelitis does in fact have unique differences, said Avindra Nath, MD, chief of the Section of Infections of the Nervous System and clinical director of the National Institute of Neurological Disorders and Stroke.
“The poliovirus is transmitted through water or food. It has an oro-fecal transmission, and sometimes causes gastrointestinal symptoms. But enterovirus D68, which is the presumptive agent here, is spread through the air and can be isolated from the nasal passages. It’s going to affect muscles supplied by the cervical spinal cord and the brainstem.”
Look for the full article and discussion in the Nov. 16 issue of Neurology Today. For more coverage of the outbreak, browse Neurology Today's archives at http://bit.ly/1pwNJh1.
To report a case of acute flaccid myelitis to your state health department, or to see updated information from the CDC, go to http://bit.ly/entero-cdc. Some neurologists are sharing their observations on a child neurology listserv at http://bit.ly/listserv-cn.
Neurologists may also invite families to participate in an online registry and data repository organized by University of Texas Southwestern Medical Center. To find out more, families can send an email to firstname.lastname@example.org.
Monday, October 13, 2014
by Rebecca Hiscott
New research continues to provide evidence of an important link between a healthy body and a healthy brain. A recent study published in the Oct. 8 online issue of Neurology has strengthened that association with the finding that a healthy diet, moderate alcohol consumption, no history of smoking, physical activity, and healthy body weight can effectively halve the risk of stroke for middle-aged women.
Image via with wind on Flickr.
Researchers at the Karolinska Instituet in Stockholm, Sweden, looked at data from 31,696 women enrolled in the Swedish Mammography Cohort, a study that examined the link between modifiable lifestyle factors and major chronic diseases. At the beginning of the study, all participants completed a 350-item questionnaire about diet and lifestyle factors such as education, body weight, smoking history, physical activity, and alcohol consumption.
The researchers then identified and tracked five “low-risk lifestyle factors” among the study population: a healthy diet, defined as frequent consumption of foods such as fruits, vegetables, whole grains, fish, and low-fat dairy products; moderate alcohol consumption, defined as between three and nine drinks per week; no history of smoking; physical activity, defined as walking or biking for at least 40 minutes per day; and a healthy Body Mass Index (BMI) of less than 25.
Most women in the study met the criteria for two or three of these low-risk lifestyle factors; 589 women had all five, while 1,535 had none.
The participants were followed for approximately 10 years. In that time, 1,554 women experienced a stroke, including 1,155 cerebral infarctions, which are caused a blood vessel that prevents blood and oxygen from reaching part of the brain, and 246 hemorrhagic strokes, which are caused by bleeding in or around the brain.
The researchers found that women who had all five low-risk lifestyle factors had a 54 percent lower risk of experiencing any type of stroke, and a 62 percent lower risk of experiencing a cerebral infarction, than women who had none of those factors. Across the study population, the risk of stroke decreased with each additional healthy lifestyle factor.
The results were particularly strong for cerebral infarction, which accounts for 80 to 85 percent of all strokes. The authors found that women who had a healthy diet were 13 percent less likely to experience a cerebral infarction than women with a less healthy diet, and that “smoking was the lifestyle factor that was most strongly associated with total stroke and cerebral infarction,” they wrote.
However, the researchers found no association between healthy lifestyle factors and hemorrhagic stroke, which accounts for 15 to 20 percent of all stroke cases.
The reason that a healthy lifestyle reduces stroke risk appears to be well understood. Hypertension, or high blood pressure, is a leading cause of stroke, and diet, alcohol consumption, physical activity, smoking, and obesity can all contribute to elevated blood pressure, the authors noted.
“Because the consequences of stroke are usually devastating and irreversible, prevention is of great importance,” study author Susanna C. Larsson, PhD, an assistant professor of epidemiology at the Karolinska Instituet, said in a news release. “These results are exciting because they indicate that a healthy diet and lifestyle can substantially reduce the risk of stroke, and these are lifestyle choices that people can make or improve.”
For more coverage of the link between lifestyle factors and stroke, browse our archives here: http://bit.ly/1tmblMl.
Friday, October 10, 2014
by Rebecca Hiscott
Women who experience high levels of stress and anxiety in midlife are twice as likely to develop Alzheimer’s disease as women who are less stressed, a study published in the Oct. 1 online issue of Neurology found.
Image via bottled_void on Flickr.
Swedish researchers tracked 800 women between the ages of 38 and 54 for 38 years, beginning in 1968, in order to examine the effect of neurotic personality and stress on dementia risk. The participants received baseline assessments for neuroticism and extroversion using the Eysenck Personality Inventory, a questionnaire that measures psychological traits including depression, anxiety, sociability, and positivity. At multiple points during follow-up, the researchers also assessed the subjects’ self-reported stress levels.
Over the subsequent decades, 153 women (or roughly 19 percent of participants) developed dementia, including 104 cases of Alzheimer’s disease (AD). The researchers found that women who were highly neurotic had an increased risk of developing AD dementia, but not other types of dementia (p=0.046).
After adjusting for long-term stress, defined as a period of stress lasting longer than one month, the association weakened, “suggesting that the association between AD dementia and neuroticism is at least partially mediated by a lifelong increased proneness to experience everyday life stressors as well as stressor-related distress,” the authors wrote. “It is possible that neuroticism makes the individual more vulnerable to stressors and distress, which leads to later development of dementia.”
The findings appear consistent with a past study from the group, published Sept. 30, 2013 in BMJ Open, which reported that stress in midlife is associated with age-related brain changes, including AD dementia.
Overall, the findings suggested that women who were more neurotic and less extroverted were twice as likely to develop Alzheimer’s disease dementia as women who were less neurotic and more extroverted. The authors also noted that women who were more extroverted reported lower levels of long-term stress.
The findings are significant because “the long interval (nearly 40 years) between onset of neuroticism and outcome (AD) rules out any effect of early AD pathology,” Robert Stewart, MD, a professor of psychiatric epidemiology and clinical informatics at King’s College London, who was not involved in the study, wrote in a comment published in the same issue of Neurology.
Although the study only evaluated middle-aged women, the authors said in a recent interview that the findings would likely be similar for both genders.
“Taken together, these findings are consistent with a broader truth that people who are more exposed (or more vulnerable) to the vicissitudes of life may also be less likely to ‘age well,’ whether this is measured by mortality, cardiovascular disease, AD, or other aging-related outcomes,” Dr. Stewart wrote.
The link between neuroticism and Alzheimer’s disease is correlative, not causative, the authors warned. Anxious and neurotic personality traits may contribute to a heightened risk of Alzheimer’s because of their association with lifestyle factors and behaviors that increase other risk factors for the disease, they suggested.
“Future studies should examine the etiologic pathways for the associations and test whether this group responds well to interventions,” they wrote. “It remains to be seen whether neuroticism could be modified, e.g., by medical treatment or through lifestyle changes.
For more coverage of risk factors for Alzheimer’s disease and dementia, browse our archives here: http://bit.ly/NN-AlzheimersDementia.