1. APA study suggests patients more likely to refuse drug therapy than psychotherapy for mental health

    March 23, 2017 by Ashley

    From the American Psychological Association press release:

    People seeking help for mental disorders are more likely to refuse or not complete the recommended treatment if it involves only psychotropic drugs, according to a review of research published by the American Psychological Association.

    Researchers conducted a meta-analysis of 186 studies of patients seeking help for mental health issues that examined whether they accepted the treatment that was recommended and if they did, whether they completed it. Fifty-seven of the studies, comprising 6,693 patients, had a component that reported refusal of treatment recommendations, and 182 of the studies, comprising 17,891 patients, had a component reporting premature termination of treatment.

    After diagnosis, patients in the studies were recommended to drug-only therapy (pharmacotherapy), talk therapy (psychotherapy) or a combination of the two.

    “We found that rates of treatment refusal were about two times greater for pharmacotherapy alone compared with psychotherapy alone, particularly for the treatment of social anxiety disorder, depressive disorders and panic disorder,” said lead researcher Joshua Swift, PhD, of Idaho State University. “Rates of premature termination of therapy were also higher for pharmacotherapy alone, compared with psychotherapy alone, particularly for anorexia/bulimia and depressive disorders.”

    The research was published in the APA journal Psychotherapy.

    Across all the studies, the average treatment refusal rate was 8.2 percent. Patients who were offered pharmacotherapy alone were 1.76 times more likely to refuse treatment than patients who were offered psychotherapy alone. Once in treatment, the average premature termination rate was 21.9 percent, with patients on drug-only regimens 1.2 times more likely to drop out early. There was no significant difference for refusal or dropout rates between pharmacotherapy alone and combination treatments, or between psychotherapy alone and combination treatments.

    While Swift said the findings overall were expected, the researchers were most surprised by how large the differences were for some disorders. For example, patients diagnosed with depressive disorders were 2.16 times more likely to refuse pharmacotherapy alone and patients with panic disorders were almost three times more likely to refuse pharmacotherapy alone.

    The findings are especially interesting because, as a result of easier access, recent trends show that a greater percentage of mental health patients in the U.S. are engaging in pharmacotherapy than psychotherapy, according to co-author Roger Greenberg, PhD, SUNY Upstate Medical University.

    Some experts have argued that psychotherapy should be the first treatment option for many mental health disorders. Those arguments have been largely based on good treatment outcomes for talk therapy with fewer side effects and lower relapse rates, said Greenberg. “Our findings support that argument, showing that clients are more likely to be willing to start and continue psychotherapy than pharmacotherapy.”

    Swift and Greenberg theorized that patients may be more willing to engage in psychotherapy because many individuals who experience mental health problems recognize that the source of their problems may not be entirely biological.

    “Patients often desire an opportunity to talk with and work through their problems with a caring individual who might be able to help them better face their emotional experiences,” said Greenberg. “Psychotropic medications may help a lot of people, and I think some do see them as a relatively easy and potentially quick fix, but I think others view their problems as more complex and worry that medications will only provide a temporary or surface level solution for the difficulties they are facing in their lives.”

    While the meta-analysis provides information on refusal and dropout rates, the studies did not report the patients’ reasons for their actions, Swift noted. Going forward, research designed to identify these reasons could lead to additional strategies to improve initiation and completion rates for both therapies, he said. It is also important to note that participants in the research studies initially indicated they were willing to be assigned to any therapy, and therefore may not be representative of all consumers of treatment.


  2. Benzodiazepines, related drugs increase stroke risk among persons with Alzheimer’s disease

    January 25, 2017 by Ashley

    From the University of Eastern Finland media release:

    memory lossThe use of benzodiazepines and benzodiazepine-like drugs was associated with a 20 per cent increased risk of stroke among persons with Alzheimer’s disease, shows a recent study from the University of Eastern Finland. Benzodiazepines were associated with a similar risk of stroke as benzodiazepine-like drugs.

    The use of benzodiazepines and benzodiazepine-like drugs was associated with an increased risk of any stroke and ischemic stroke, whereas the association with hemorrhagic stroke was not significant. However, due to the small number of hemorrhagic stroke events in the study population, the possibility of such an association cannot be excluded. The findings are important, as benzodiazepines and benzodiazepine-like drugs were not previously known to predispose to strokes or other cerebrovascular events. Cardiovascular risk factors were taken into account in the analysis and they did not explain the association.

    The findings encourage a careful consideration of the use of benzodiazepines and benzodiazepine-like drugs among persons with Alzheimer’s disease, as stroke is one of the leading causes of death in this population group. Earlier, the researchers have also shown that these drugs are associated with an increased risk of hip fracture.

    The study was based on data from a nationwide register-based study (MEDALZ) conducted at the University of Eastern Finland in 2005-2011. The study population included 45,050 persons diagnosed with Alzheimer’s disease, and 22 per cent of them started using benzodiazepines or benzodiazepine-like drugs.

    The findings were published in International Clinical Psychopharmacology.


  3. The first-in-human clinical trial targeting Alzheimer’s tau protein

    December 13, 2016 by Ashley

    From the Karolinska Institutet media release:

    So far, many of the antibody drugs proposed to treat Alzheimer’s disease target only the amyloid plaques. Despite the latest clinical trial that is hailed as our best chance in the quest for treating AD, all later phase trials have failed with many causing severe side effects in the patients, such as abnormal accumulation of fluid and inflammation in the brain. One of the reasons for side effects, many speculate, is due to the antibody directing a reaction towards normal amyloid present in blood vessels or simply releasing beta-amyloid caught in the vessel wall.

    The authors of the study have developed a vaccine that stimulates the production of an antibody that specifically targets pathological tau, discovering its “Achilles’ heel.” It is able to do this because healthy tau undergoes a series of changes to its structure forming a new region that the antibody attacks. This new region (the “Achilles’ heel”), while not present in healthy tau, is present in diseased tau early on. Therefore, the antibody tackles all the different varieties of pathological tau. In addition to this important specificity, the antibody is coupled to a carrier molecule that generates a considerable immune response with the added benefit that it is not present in humans, thus avoiding the development of an immune reaction towards the body itself.

    Side effects have included a local reaction at the site of injection. This skin reaction is thought to occur due to the aluminum hydroxide, an adjuvant used in vaccines to enhance the body’s own antibody production. No other serious secondary effects were directly related to the vaccine. Overall, the safety of the drug and its ability to elicit an immune response were remarkable.

    While many trials against Alzheimer’s disease stubbornly continue to target amyloid, our study dares to attack the disease from another standpoint. This is the first active vaccination to harness the body’s ability to produce antibodies against pathological tau. Even though this study is only a phase 1 trial, its success so far gives the authors confidence that it may be the answer they are looking for to halt the progress of this devastating disease.


  4. Researchers use video gamelike test to study learning and recovery in stroke patients

    October 31, 2016 by Ashley

    From the Johns Hopkins Medicine media release:

    hospital stayA robotic arm and a virtual game were essential tools in a new study from researchers at Johns Hopkins Medicine. The study results suggest that while training doesn’t change neurological repair in chronic stroke patients, it can indeed help such patients learn new motor skills and achieve more independence in their daily lives.

    A report on the work is published in the journal Neurorehabilitation and Neural Repair on Oct. 27.

    “What we found is that physical rehab is not going to change the weakness caused by damaged brain cells in chronic patients, but it is going to change how well they can perform certain tasks, which can have a huge impact on a patient’s daily life,” says Pablo Celnik, M.D., director of the Department of Physical Medicine and Rehabilitation at Johns Hopkins.

    Brain damage from strokes occurs when the blood supply to the brain is blocked (ischemic stroke) or a blood vessel feeding brain tissue ruptures (hemorrhagic stroke). Depending on the extent of the stroke, the damage can cause partial or total paralysis, affecting motor function, balance, speech, sensation and other physical activities. Chronic stroke patients are those whose physical impairments persist more than six months after the stroke. Rehabilitation specialists measure the damage using the Fugl-Meyer Assessment (FMA), which measures the neurological damage wrought by a stroke on a scale from zero to 66.

    For the new study, the investigators recruited 10 chronic stroke patients with FMA scores of ?50 out of 66 and categorized them as having “mild to moderate” functional deficits for the purposes of the study, and 10 other patients with FMA scores of <50 out of 66 and categorized them as having “moderate to severe” impairment. A third group of 10 able-bodied participants served as a control group.

    All of the study participants were trained to control a simple video game using a using a robotic piece of equipment that held their dominant arm at 90 degrees from their bodies. This eliminated gravity as a burden for those whose arms were weakened by their strokes. The subjects were then taught to use the muscles around their elbow to move a cursor across a screen into small target windows.

    Participants’ performance in the game was measured during training sessions and skill assessment trials. A pre-training skill assessment was conducted to get a baseline from which to measure improvement. Participants were asked to move the cursor through the windows in time with a metronome and completed nine blocks of 10 trials at various speeds — 24, 30, 38, 45, 60, 80, 100, 110 and 120 beats per minute. The metronome prevented participants from slowing down to improve their accuracy, so the only way to show improvement was by becoming more skilled at the task.

    The next phase of the experiment had participants attend 30-minute training sessions for four consecutive days. They were asked to complete five blocks of 30 trials, all at their own pace, and were encouraged to improve their speed and accuracy in each consecutive block. Following the training sessions, participants’ skill levels were tested again in another skill assessment.

    Results showed that while each group’s skill level improved by the end of the training, those with greater motor impairment still demonstrated less skill in both the pre- and post-training assessments. All participants reached a plateau in their improvement around experimental days three and four.

    However, the study showed that there was considerable overlap between the post-training performance of the stroke patients and the pre-training performance of groups with less impairment. “When you look at the data, the post-training mild-to-moderate group is indistinguishable from the pre-training control group. And the same was true for post-training scores of those in the moderate-to-severe group and the mild-to-moderate group,” says Robert Hardwick, Ph.D., postdoctoral fellow in the Department of Neurology at the Johns Hopkins University School of Medicine.

    This is good news for patients because it means that even when there is little likelihood of further neurological recovery, it means I can still teach them new tasks through training,” says Celnik. “What is important is to not create false expectations of neurological recovery, while at the same time being hopeful that patients can learn within the boundaries of their neurological deficit to improve their lives.”

    According to the World Health Organization, 15 million people worldwide suffer a stroke each year. An estimated 5 million die, and another 5 million are left with lasting motor impairment. Celnik cautions that this study only included chronic stroke patients and that their future research plans include conducting similar studies in acute stroke patients — those within three months of the stroke — which could yield different results. “Maybe there is a different impact of training in the earlier stages of stroke damage,” says Celnik.


  5. Nondrug approaches effective for treatment of common pain conditions, review suggests

    September 21, 2016 by Ashley

    From the NIH/National Center for Complementary and Integrative Health media release:

    yoga matsData from a review of U.S.-based clinical trials published in Mayo Clinic Proceedings suggest that some of the most popular complementary health approaches — such as yoga, tai chi, and acupuncture — appear to be effective tools for helping to manage common pain conditions. The review was conducted by a group of scientists from the National Center for Complementary and Integrative Health (NCCIH) at the National Institutes of Health.

    Millions of Americans suffer from persistent pain that may not be fully relieved by medications. They often turn to complementary health approaches to help, yet primary care providers have lacked a robust evidence base to guide recommendations on complementary approaches as practiced and available in the United States. The new review gives primary care providers — who frequently see patients with chronic pain — tools to inform decision-making on how to help manage that pain.

    “For many Americans who suffer from chronic pain, medications may not completely relieve pain and can produce unwanted side effects. As a result, many people may turn to nondrug approaches to help manage their pain,” said Richard L. Nahin, Ph.D., NCCIH’s lead epidemiologist and lead author of the analysis. “Our goal for this study was to provide relevant, high-quality information for primary care providers and for patients who suffer from chronic pain.”

    The researchers reviewed 105 U.S.-based randomized controlled trials, from the past 50 years, that were relevant to pain patients in the United States and met inclusion criteria. Although the reporting of safety information was low overall, none of the clinical trials reported significant side effects due to the interventions.

    The review focused on U.S.-based trial results on seven approaches used for one or more of five painful conditions — back pain, osteoarthritis, neck pain, fibromyalgia, and severe headaches and migraine — and found promise in the following for safety and effectiveness in treating pain:

    • Acupuncture and yoga for back pain
    • Acupuncture and tai chi for osteoarthritis of the knee
    • Massage therapy for neck pain with adequate doses and for short-term benefit
    • Relaxation techniques for severe headaches and migraine.

    Though the evidence was weaker, the researchers also found that massage therapy, spinal manipulation, and osteopathic manipulation may provide some help for back pain, and relaxation approaches and tai chi might help people with fibromyalgia.

    “These data can equip providers and patients with the information they need to have informed conversations regarding non-drug approaches for treatment of specific pain conditions,” said David Shurtleff, Ph.D., deputy director of NCCIH. “It’s important that continued research explore how these approaches actually work and whether these findings apply broadly in diverse clinical settings and patient populations.”

     


  6. Borderline personality disorder: As scientific understanding increases, improved clinical management needed

    September 8, 2016 by Ashley

    From the Wolters Kluwer Health media release:

    abused woman domestic violenceEven as researchers gain new insights into the neurobiology of borderline personality disorder (BPD), there’s a pressing need to improve diagnosis and management of this devastating psychiatric condition. A scientific and clinical research update on BPD is presented in the September/October special issue of the Harvard Review of Psychiatry, published by Wolters Kluwer.

    The special issue comprises seven papers, contributed by experts in the field, providing an integrated overview of research and clinical management of BPD. “We hope these articles will help clinicians understand their BPD patients, encourage more optimism about their treatability, and help set a stage from which the next generation of mental health professionals will be more willing to address the clinical and public health challenges they present,” according to a guest editorial by Drs. Lois Choi-Kain and John Gunderson of the Adult Borderline Center and Training Institute at McLean Hospital, Belmont, Mass.

    Borderline Personality Disorder — Research Advances, Emerging Clinical Approaches

    Although the diagnostic criteria for BPD are well-accepted, it continues to be a misunderstood and sometimes neglected condition; many psychiatrists actively avoid making the diagnosis. Borderline personality disorder accounts for nearly 20 percent of psychiatric hospitalizations and outpatient clinic admissions, but only three percent of the research budget of the National Institute of Mental Health. (The NIMH provides information about BPD online at http://www.nimh.nih.gov/health/topics/borderline-personality-disorder)

    The Guest Editors hope their special issue will contribute to overcoming the disparity between BPD’s public health importance and the attention received by psychiatry. Highlights include:

    • A research update on the neurobiology of BPD. Evidence suggests that chronic stress exposure may lead to changes in brain metabolism and structure, thus affecting the processing and integration of emotion and thought. This line of research might inform new approaches managing BPD — possibly including early intervention to curb the neurobiological responses to chronic stress.
    • The urgent need for earlier intervention. A review highlights the risk factors, precursors, and early symptoms of BPD and mood disorders in adolescence and young adulthood. While the diagnosis of BPD may be difficult to make during this critical period, evaluation and services are urgently needed.
    • The emergence of evidence-based approaches for BPD. While these approaches have raised hopes for providing better patient outcomes, they require a high degree of specialization and treatment resources. A stepped-care approach to treatment is proposed, using generalist approaches to milder and initial cases of BPD symptoms, progressing to more intensive, specialized care based on clinical needs.
    • The critical issue of BPD in the psychiatric emergency department. This is a common and challenging situation in which care may be inconsistent or even harmful. A clinical vignette provides mental health professionals with knowledge and insights they can use as part of a “caring, informed, and practical” approach to helping BPD patients in crisis.

    The special issue also addresses the critical issue of resident training — preparing the next generation of mental health professionals to integrate research evidence into more effective management for patients and families affected by BPD. Drs. Choi-Kain and Gunderson add, “For clinicians, educators, and researchers, we hope this issue clarifies an emerging basis for earlier intervention, generalist approaches to care for the widest population, and a more organized approach to allocating care for individuals with BPD.”


  7. New neuroendovascular technique shows promise in stroke patients with large-vessel clots

    June 30, 2016 by Ashley

    From the Medical University of South Carolina media release:

    hospital emergency signIn an article published online April 16, 2016 by the Journal of Neurointerventional Surgery, investigators at the Medical University of South Carolina (MUSC) report promising 90-day outcomes for stroke patients with large-vessel clots who underwent thrombectomy or clot removal using the direct-aspiration, first pass technique (ADAPT). Approximately 58% of stroke patients with a large-vessel clot removed using the technique achieved a good outcome at 90 days, defined as a Modified Rankin Score (mRS) of 0 to 2.

    ADAPT aims to remove the clot in its entirety with a large-diameter aspiration catheter in a single pass. In contrast, stent retrievers, currently considered standard of care, frequently fragment the clot for removal and can require several passes.

    ADAPT was developed by MUSC Health neuroendovascular surgeons M. Imran Chaudry, M.D., Alejandro M. Spiotta, M.D., Aquilla S. Turk, D.O., and Raymond D. Turner, M.D., all co-authors on the April 2016 Journal of Neurointerventional Surgery article. MUSC Health neurosurgery resident Jan Vargas, M.D., is first author on the article.

    The goal in ADAPT is to take the largest-bore catheter available up to the blood clot and put suction where it’s blocked and pull it out of the head to reestablish flow in that blood vessel,” said Turk. If the first-pass attempt is unsuccessful, stent retrievers can still be used to remove the clot.

    In the article, the investigators report the results of a retrospective study of 191 consecutive patients with acute ischemic stroke who underwent ADAPT at MUSC Health. In 94.2% of patients, blood vessels were successfully opened–by direct aspiration alone in 145 cases and by the additional use of stent retrievers in another 43 cases. Good outcomes at 90 days (mRS, 0-2) were achieved in 57.7% of patients who were successfully revascularized with aspiration alone and in 43.2% of those who also required a stent retriever. The average time required to reopen the blocked blood vessels was 37.3 minutes–29.6 minutes for direct aspiration alone and 61.4 minutes for cases that also required stent retrievers. Patients presented for thrombectomy on average 7.8 hours after stroke onset.

    These results confirm the promise of ADAPT, which was first described by the MUSC Health team in a seminal 2014 article in the Journal of Neurointerventional Surgery. Since the publication of that article, a number of single-center series studies have reported impressive recanalization times (the time it takes to open the blood vessel) and good neurological outcomes with ADAPT using a large-bore catheter, suggesting that it could offer an alternative approach to stent retrievers for mechanical thrombectomy.

    Stent retrievers have been considered standard of care for stroke patients since the publication in the October 2015 issue of Stroke of a scientific statement on thrombectomy by the American Heart Association. That statement recommended rapid clot removal in addition to tissue plasminogen activator (tPA), a clot-busting drug that can minimize stroke complications if administered in a tight time window. The recommendation was based on the promising findings of five large clinical trials comparing treatment with tPA alone versus treatment with tPA plus thrombectomy using stent retrievers in large-vessel clots: MR CLEAN, EXTEND-IA, ESCAPE, SWIFT PRIME, and REVASCAT.

    A definitive answer as to whether ADAPT could likewise become standard of care for stroke patients with large-vessel clots will require clinical trials comparing the efficacy of the direct aspiration technique versus stent retrievers in this population of stroke patients.

    The MUSC Health neuroendovascular surgery team is currently running the COMPASS trial (COMParison of ASpiration vs Stent retriever as first-line approach; Clinicaltrials.gov identifier NCT02466893) in conjunction with colleagues Dr. J. Mocco of Mount Sinai and Dr. Adnan Siddiqui of the University of Buffalo. The trial is randomizing patients to either ADAPT or a stent retriever as the initial thrombectomy technique. The trial, scheduled to enroll 270 patients, has enrolled 90 patients in the past year at ten sites in the United States.


  8. Standard blood pressure target is sufficient for treating some strokes

    June 13, 2016 by Ashley

    From the NIH/National Institute of Neurological Disorders and Stroke media release:hospital emergency sign

    An international stroke study found that standard and intensive blood pressure treatments were equally effective in the emergency treatment of acute intracerebral hemorrhage, a type of stroke caused by bleeding into the brain.

    Patients whose systolic blood pressure was reduced rapidly in emergency rooms to standard levels used to treat acute stroke (140-179 mm Hg) did as well as patients whose pressure was reduced to intensive levels (110-139 mm Hg). The study, published in the New England Journal of Medicine, was funded by the NIH’s National Institute of Neurological Disorders and Stroke (NINDS).

    For decades, doctors wondered whether intensive blood pressure management was more effective than standard treatment for controlling intracerebral hemorrhage,” said Adnan I. Qureshi, M.D., professor of Neurology, Neurosurgery and Radiology, Zeenat Qureshi Stroke Research Center, University of Minnesota, Minneapolis, the principal investigator of the study. “Our results may help patients and their doctors make better treatment decisions.”

    Annually, more than 795,000 people in the U.S. have a stroke. Approximately 10 percent of strokes are caused by acute intracerebral hemorrhages. Chronic high blood pressure is the greatest risk factor for these types of strokes. Studies have shown that controlling blood pressure reduces the chances of having all types of strokes. Although this type of stroke is associated with higher rates of death or disability than the more common form caused by brain blood clots, there is a need for scientifically proven emergency treatments for hemorrhage strokes.

    Elevated blood pressure is thought to contribute to growth of the hemorrhage, or the leak, and worse outcomes. Some studies have suggested that rapid, intensive blood pressure lowering may lead to better outcomes. Nonetheless, the ideal target blood pressure to minimize hemorrhage growth safely and effectively has not been established.

    The Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH II) trial addressed this issue by randomly assigning 1,000 participants with elevated blood pressure following their stroke to either standard or intensive blood pressure treatments used for acute stroke. The participants, who on average were 62 years old, were treated within four and a half hours of a stroke at medical centers in the U.S., Japan, Taiwan, China, South Korea and Germany.

    On average, the participants entered the trial with a blood pressure level of 200.6 mm Hg. Their high levels were lowered by intravenous injections of nicardipine, a blood pressure medication. Overall the standard and intensive blood pressure treatment levels were higher than normal (120 mm Hg or less).

    Rapidly lowering blood pressure to normal levels may further damage the brain,” said Dr. Qureshi. “The levels we used are tolerable for emergencies. Normal levels can be safely obtained gradually.”

    Brain scans taken 24 hours after treatment showed no difference in the rates of hemorrhage growth between the two groups. The results also showed that after 90 days the rate of death or severe disability was equal, about 38 percent, for either treatment. Patients in the intensive treatment group had a slightly higher rate of serious adverse events in the 90 days following the stroke.

    “The NIH is committed to saving lives and rescuing stroke patients from life-long disability,” said Walter J. Koroshetz, M.D., director of the NINDS. “Studies like ATACH II provide doctors with the most rigorously tested information to guide emergency treatment options.”

    The study was designed to enroll 1,280 patients; the researchers stopped the trial after analyzing data from the first 1,000 patients, however, because they saw no differences between the treatments.

    The 90-day death and severe disability rates of this study were lower than those seen in other hemorrhagic stroke studies, 38 percent versus an expected rate of 60 percent. The researchers suggested that the difference may be due to including patients who had relatively minor strokes and therefore a better chance of good results. Initial patient examinations showed that over half had mild stroke as determined by the Glasgow Coma Scale. The researchers also suggested that, by participating in the trial, the patients received better overall care.

    “Although additional studies are needed, we may have seen a global benefit of careful monitoring and standardized care for patients with acute cerebral hemorrhage,” said Dr. Qureshi.


  9. Antibiotics that kill gut bacteria also stop growth of new brain cells

    May 23, 2016 by Ashley

    From the Cell Press media release:

    magnesium pillsAntibiotics strong enough to kill off gut bacteria can also stop the growth of new brain cells in the hippocampus, a section of the brain associated with memory, reports a study in mice published May 19 in Cell Reports. Researchers also uncovered a clue to why– a type of white blood cell seems to act as a communicator between the brain, the immune system, and the gut.

    “We found prolonged antibiotic treatment might impact brain function,” says senior author Susanne Asu Wolf of the Max-Delbrueck-Center for Molecular Medicine in Berlin, Germany. “But probiotics and exercise can balance brain plasticity and should be considered as a real treatment option.”

    Wolf first saw clues that the immune system could influence the health and growth of brain cells through research into T cells nearly 10 years ago. But there were few studies that found a link from the brain to the immune system and back to the gut.

    In the new study, the researchers gave a group of mice enough antibiotics for them to become nearly free of intestinal microbes. Compared to untreated mice, the mice who lost their healthy gut bacteria performed worse in memory tests and showed a loss of neurogenesis (new brain cells) in a section of their hippocampus that typically produces new brain cells throughout an individual’s lifetime. At the same time that the mice experienced memory and neurogenesis loss, the research team detected a lower level of white blood cells (specifically monocytes) marked with Ly6Chi in the brain, blood, and bone marrow. So researchers tested whether it was indeed the Ly6Chi monocytes behind the changes in neurogenesis and memory.

    In another experiment, the research team compared untreated mice to mice that had healthy gut bacteria levels but low levels of Ly6Chi either due to genetics or due to treatment with antibodies that target Ly6Chi cells. In both cases, mice with low Ly6Chi levels showed the same memory and neurogenesis deficits as mice in the other experiment who had lost gut bacteria. Furthermore, if the researchers replaced the Ly6Chi levels in mice treated with antibiotics, then memory and neurogenesis improved.

    For us it was impressive to find these Ly6Chi cells that travel from the periphery to the brain, and if there’s something wrong in the microbiome, Ly6Chi acts as a communicating cell,” says Wolf.

    Luckily, the adverse side effects of the antibiotics could be reversed. Mice who received probiotics or who exercised on a wheel after receiving antibiotics regained memory and neurogenesis. “The magnitude of the action of probiotics on Ly6Chi cells, neurogenesis, and cognition impressed me,” she says.

    But one result in the experiment raised more questions about the gut’s bacteria and the link between Ly6Chi and the brain. While probiotics helped the mice regain memory, fecal transplants to restore a healthy gut bacteria did not have an effect.

    “It was surprising that the normal fecal transplant recovered the broad gut bacteria, but did not recover neurogenesis,” says Wolf. “This might be a hint towards direct effects of antibiotics on neurogenesis without using the detour through the gut. To decipher this we might treat germ free mice without gut flora with antibiotics and see what is different.”

    In the future, researchers also hope to see more clinical trials investigating whether probiotic treatments will improve symptoms in patients with neurodegenerative and psychiatric disorders.”We could measure the outcome in mood, psychiatric symptoms, microbiome composition and immune cell function before and after probiotic treatment,” says Wolf.


  10. Migraine drugs underused, research suggests

    May 13, 2016 by Ashley

    From the Thomas Jefferson University media release:

    aspirinAbout 38 million Americans suffer from migraines in the United States, according to the Migraine Research Foundation.

    The most commonly used and effective classes of medication, triptans and DHE (Dihydroergotamine), however, have a black box warning for two subtypes of migraine because of risk of stroke. Now researchers at Abington-Jefferson Health have shown that patients who were given the drugs off-label had no stroke or other cardiovascular side-effects from taking the drugs.

    Not only does the study suggest these drugs are safe for this subset of migraine patients, it could also have implications for the nearly 10 million migraine sufferers who experience auras — a disturbance in vision, touch, speech, thinking, or strength that usually precedes a migraine headache.

    “There are not enough medicines out there to appropriately manage migraine headaches,” says senior author Brad Klein, M.D., Medical Director of the Headache Center at Abington Hospital-Jefferson Health. “At a time in history when an unprecedented number of people are getting hooked on narcotic opiates by way of prescribed medications — as is the case with migraine sufferers as well — we owe it to ourselves as physicians to try medications that could work without the risk of addiction,” says Klein. The study was published in the journal Headache.

    Migraines are thought to cause pain because they cause a swelling of the blood vessels feeding the brain. However, two subtypes of migraines, basilar and hemiplegic, are thought to cause pain by doing the opposite — constricting rather than swelling the blood vessels of the brain. Triptans and DHE are both thought to relieve migraine, in part, by constricting blood vessels. Early on, drug developers worried that adding more constriction to basilar and hemiplegic migraines could put these patients at greater risk of stroke, so these patients were excluded from the initial studies. “As a result,” says Klein, “no one ever actually showed that these drugs were dangerous — they were just assumed to be dangerous based on their mechanism of action. And recent research suggests that the auras are not due to blood vessel constriction.”

    To determine whether there was any increased risk of stroke in basilar and hemiplegic patients taking triptans or DHE, Klein and researchers at Brigham and Women’s Hospital in Boston did a retrospective analysis, collecting data from four headache centers around the country. They searched for patients who had symptoms pointing to a basilar or hemiplegic migraine diagnosis and also received either a triptan or DHE treatment. Of the 80 patients they identified, they saw no cases of stroke or heart attack during the period of routine follow up, over several months.

    Although others had studied this effect before, this research had the largest patient cohort to date, and was also one of the first to examine patients treated with DHE.

    Migraines can be very complex to diagnose and there are few certified headache specialists in the United States — only 500 for the 38 million sufferers, according to the Migraine Research Foundation. “Because auras are associated with basilar and hemiplegic migraine, many physicians refuse to give these drugs to any patients experiencing an aura out of a false sense of precaution,” says Dr. Klein. Instead migraine sufferers may be given other, less effective drugs such as opioid narcotics.