<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_444"
                     title="Huntington Drug Produces Slight Benefit (CME/CE)"
                     score="0.014"
                     href="http://www.medpagetoday.com/Neurology/GeneralNeurology/tb/18363?impressionId=1265799800073"
                     
      &lt;p&gt;An investigational drug that protects mitochondria in nerve cells helped restore some cognitive function in patients with Huntington&apos;s disease, researchers said.&lt;/p&gt;
&lt;p&gt;Patients receiving three months of treatment with latrepirdine (Dimebon), formerly known as dimebolin, showed a mean increase of 0.86 points (SD 0.31) on the Mini-Mental State Exam (MMSE), compared to an average decline of 0.12 points (SD 0.31,&lt;em&gt; P&lt;/em&gt;=0.03) in a placebo group, Karl Kieburtz, MD, MPH, at the University of Rochester in Rochester, N.Y., and colleagues reported in the February &lt;em&gt;Archives of Neurology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The treatment was also well tolerated in the 91-patient randomized trial, though no differences from placebo were seen in other measures of efficacy, including the Unified Huntington&apos;s Disease Rating Scale and the cognition component of the Alzheimer&apos;s Disease Assessment Scale.&lt;/p&gt;
&lt;p&gt;Kieburtz and colleagues concluded that latrepirdine &quot;may have a beneficial effect on cognition&quot; in Huntington&apos;s disease patients and that additional trials are warranted.&lt;/p&gt;
&lt;p&gt;Latrepirdine stabilizes the mitochondrial membrane in neurons. Disruption in the membrane leads to neuronal apoptosis and appears to play a role in neuron death associated with several neurodegenerative syndromes, including Huntington&apos;s and Alzheimer&apos;s diseases, the authors noted.&lt;/p&gt;
&lt;p&gt;&quot;Nonclinical data available to date suggest that the mechanism of action of latrepirdine is to enhance mitochondrial function in the setting of cellular stress,&quot; Kieburtz and colleagues explained in the report.&lt;/p&gt;
&lt;p&gt;A phase III study of latrepirdine in Alzheimer&apos;s disease, &lt;a href=&quot;http://www.medpagetoday.com/Geriatrics/AlzheimersDisease/10174&quot; mce_href=&quot;http://www.medpagetoday.com/Geriatrics/AlzheimersDisease/10174&quot; target=&quot;_blank&quot;&gt;reported in 2008&lt;/a&gt;, produced modest benefits. Two additional phase III trials were started late last year, according to the drug&apos;s co-developers, Medivation and Pfizer.&lt;/p&gt;
&lt;p&gt;The drug was once sold in Russia as a nasal decongestant, but is no longer available anywhere.&lt;/p&gt;
&lt;p&gt;The drug&apos;s generic name was originally dimebolin but the companies requested the change to latrepirdine last year.&lt;/p&gt;
&lt;p&gt;In the current study, designed primarily as a safety assessment, Kieburtz and colleagues randomized middle-age patients with mild to moderate Huntington&apos;s disease symptoms to either placebo or 20 mg of latrepirdine three times daily.&lt;/p&gt;
&lt;p&gt;Adverse events of various types were reported in 70% of the latrepirdine patients and 80% of the placebo group. Falls, headache, dizziness, nausea, and chorea were the most common in both groups, with no significant differences in rates between the drug and placebo.&lt;/p&gt;
&lt;p&gt;Headache (three cases) and somnolence (three cases) were somewhat more common with latrepirdine than with placebo ( three cases and one case, respectively).&lt;/p&gt;
&lt;p&gt;On none of the 11 motor or cognitive components of the Unified Huntington&apos;s Disease Rating Scale did patients receiving latrepirdine show a significant difference from the placebo group.&lt;/p&gt;
&lt;p&gt;Patients showed similar declines in mean scores on the Alzheimer&apos;s Disease Assessment Scale&apos;s cognitive component, both decreasing about one point from a mean at baseline of 20.&lt;/p&gt;
&lt;p&gt;Mean baseline scores on the MMSE were 25.3. The 0.97-point advantage of latrepirdine over placebo in this measure after 90 days was statistically significant (95% CI 0.10 to 1.85), although the clinical change was relatively small.&lt;/p&gt;
&lt;p&gt;However, Kieburtz and colleagues expressed surprise at finding any significant difference in this measure, &quot;given that the MMSE is generally considered a relatively insensitive measure of cognitive function.&quot;&lt;/p&gt;
&lt;p&gt;They indicated that the MMSE provides a broader measure of cognitive function than either the Huntington- or Alzheimer-specific instruments. The Unified Huntington&apos;s Disease Rating Scale is intended for monitoring long-term changes in function, rather than the effects of a short-term intervention such as this one, the researchers argued.&lt;/p&gt;
&lt;p&gt;They added that the Alzheimer assessment may not fully capture the cognitive domains most affected in Huntington&apos;s disease.&lt;/p&gt;
&lt;p&gt;Kieburtz and colleagues also pointed out that the improvements seen with latrepirdine were similar to those found in the earlier trial in Alzheimer&apos;s disease.&lt;/p&gt;
&lt;p&gt;The small number of patients and the relatively short treatment duration were limitations of the study.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was funded by Medivation.&lt;/p&gt;&lt;p&gt;Study authors reported relationships other than research support with Medivation, Abbott Laboratories, Biogen Idec, Ceregene, EMD Serono, FoldRx, Impax, Ipsen, Eli Lilly, Lundbeck, Merz, NeuroSearch, Novartis, Orion Health, Prestwick Pharmaceuticals, Schering-Plough, Solvay SA, Teva, UCB Pharma, Pfizer, and the Welding Rod Litigation defendants.&lt;/p&gt;&lt;p&gt;Two co-authors were employees of Medivation.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_390"
                     title="Vegetative State May Still Harbor Consciousness (CME/CE)"
                     score="0.012"
                     href="http://www.medpagetoday.com/Neurology/GeneralNeurology/tb/18283?impressionId=1265799800073"
                     
      Researchers in England are reporting they have been able to establish limited communication with a man in a persistent vegetative state by using functional magnetic resonance imaging (fMRI).&lt;br&gt;
&lt;br&gt;The 34-year-old man was able to answer simple Yes or No questions by imagining different types of activity, which caused changes in brain activity that could be seen in the machine, according to Martin Monti, PhD, of the Medical Research Council Cognition and Brain Sciences Unit in Cambridge, England, and colleagues.&lt;br&gt;
&lt;br&gt;The finding shows that at least some patients who are otherwise unresponsive may have some residual awareness, the researchers reported online in the &lt;em&gt;New England Journal of Medicine&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;&quot;The incredible thing is that we could never do something like that at the bedside,&quot; Monti told &lt;em&gt;MedPage Today&lt;/em&gt;. Outside of the fMRI machine, he said, the patient remained unresponsive to standard tests.&lt;br&gt;
&lt;br&gt;The study is likely to arouse controversy, Monti conceded, especially in the light of such high-profile cases as that of Terry Schiavo, which eventually went to the U.S. Supreme Court.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;In the Schiavo case, relatives were bitterly divided on whether to withdraw&lt;strong&gt; &lt;/strong&gt;life support for the woman, who had been in a persistent vegetative state for several years.&lt;/p&gt;
&lt;p&gt;&quot;People will have a tendency to overinterpret this,&quot; Monti said, adding &quot;this finding in one patient does not imply that all patients may or may not have the ability to do this.&quot;&lt;/p&gt;
&lt;p&gt;Indeed, the researchers tested 54 people and found only five who could apparently respond to direction by imagining either motor or spatial activity. Imagining those activities uses different parts of the brain and their activation can be seen by the fMRI scan.&lt;/p&gt;
&lt;p&gt;Several of the responders were already what is called &quot;minimally responsive,&quot; meaning that occasionally they were able to react to external stimuli.&lt;/p&gt;
&lt;p&gt;Of those five, the researchers only tried to communicate with one  --  the man in a persistent vegetative state  --  using his ability to reliably activate different brain areas when asked to imagine either playing tennis or looking around a room in his house.&lt;/p&gt;
&lt;p&gt;While in the machine, he was asked simple questions, such whether his father&apos;s name was Alexander. To answer Yes, he was to imagine playing tennis, while for No he was to imagine looking around the room.&lt;/p&gt;
&lt;p&gt;He was able to answer five out of six questions, the researchers reported, adding it was unclear why he was unable to answer the sixth but no brain activity was seen in response to the question.&lt;/p&gt;
&lt;p&gt;Outside experts also cautioned against overinterpreting the results.&lt;/p&gt;
&lt;p&gt;&quot;The percentage of patients showing a response was low, and longer-term follow-up studies are needed to determine whether such fMRI findings by themselves have meaningful predictive value,&quot; argued Alan Faden, MD, of the University of Maryland School of Medicine in Baltimore.&lt;/p&gt;
&lt;p&gt;&quot;This study may well raise questions for some with regard to medical or legal decisions based upon state of consciousness,&quot; Faden said in an e-mail, &quot;but the findings primarily underscore the limitations of current categorizations for diminished states of consciousness.&quot;&lt;/p&gt;
&lt;p&gt;He said that as technology gets better, it will likely mean that doctors will have to modify their diagnostic categories for what he called &quot;states of diminished consciousness.&quot;&lt;/p&gt;
&lt;p&gt;In an accompanying editorial in the journal, Allan Ropper, MD, of Brigham and Women&apos;s Hospital in Boston, wrote that such research is &quot;easily subject to overinterpretation and sensationalism.&quot;&lt;/p&gt;
&lt;p&gt;He cautioned that brain activation was seen only in a few patients and only in those with a traumatic brain injury, rather than global ischemia and anoxia.&lt;/p&gt;
&lt;p&gt;And, he wrote, the brain activity seen in the patients is not evidence of such things as memory, self-awareness, anxiety, or despair. &quot;We cannot be certain whether we are interacting with a sentient, much less a competent, person&quot; Ropper wrote.&lt;/p&gt;
&lt;p&gt;Despite such caveats, the research is &quot;critically important,&quot; according to Michael DeGeorgia, MD, of University Hospitals Case Medical Center in Cleveland.&lt;/p&gt;
&lt;p&gt;It &quot;illustrates both the complexities of this area and the limitations of our bedside clinical examination,&quot; he said in an e-mail, adding that more research will be needed to figure out how to use the technology and how to interpret the results.&lt;/p&gt;
&lt;p&gt;The research &quot;does raise difficult medical and legal questions,&quot; DeGeorgia said.&lt;/p&gt;
&lt;p&gt;&quot;We always need to be upfront and honest with families about what we know for certain and what we do not know for certain,&quot; he said. &quot;In many of these cases, the honest answer is that we cannot be absolutely 100% certain that their loved one isn&apos;t &apos;in there somewhere.&apos;&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study had support from the Medical Research Council, the European Commission, Fonds de la Recherche Scientifique, the James S. McDonnell Foundation, the Mind Science Foundation, the Reine Elisabeth Medical Foundation, the Belgian French-Speaking Community Concerted Research Action, University Hospital of Liege, the University of Liege, and the National Institute for Health Research Biomedical Research Centre.&lt;/p&gt;&lt;p&gt;The researchers said they had no potential conflicts.&lt;/p&gt;&lt;p&gt;Hopper did not report any conflicts.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;&lt;p&gt;&lt;em&gt;This article was developed in collaboration with ABC News. &lt;/em&gt;&lt;img src=&quot;http://www.medpagetoday.com/upload/2009/10/1/14357_1.jpg&quot; mce_src=&quot;http://www.medpagetoday.com/upload/2009/10/1/14357_1.jpg&quot; alt=&quot;&quot;&gt;&lt;/p&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_372"
                     title="Low Serotonin Eyed as Mechanism for SIDS (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/Neurology/GeneralNeurology/tb/18262?impressionId=1265799800073"
                     
      Low brainstem levels of serotonin and the enzyme that makes it could underlie sudden infant death syndrome (SIDS), researchers suggested.&lt;br&gt;
&lt;br&gt;In an autopsy study, SIDS cases showed 26% lower serotonin levels in two major components of the medulla&apos;s serotonin system  --  the raph&amp;#233; obscurus (&lt;em&gt;P&lt;/em&gt;=0.05) and paragigantocellularis lateralis (&lt;em&gt;P&lt;/em&gt;=0.04)  --  compared with age-adjusted controls who died from known causes.&lt;br&gt;
&lt;br&gt;These brainstem circuits control breathing, blood pressure, and heart rate during sleep, Hannah C. Kinney, MD, of Children&apos;s Hospital Boston, and colleagues reported in the Feb. 3 issue of the &lt;em&gt;Journal of the American Medical Association&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;A baby with an abnormality in control of these systems might not be able to respond to a life-threatening challenge like asphyxia by rousing from sleep or turning its head the researchers explained.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;SIDS occurs in the &quot;critical first year of life, when homeostatic systems are still maturing,&quot; they noted.&lt;/p&gt;
&lt;p&gt;Mary McClain, RN, MS, of Boston University Medical Center, who counsels families that have lost a baby to SIDS, commented that these findings help establish the biological basis for urging parents to place their babies on their backs to sleep.&lt;/p&gt;
&lt;p&gt;The researchers obtained tissue samples from autopsies of 41 children who died from SIDS, seven who died acutely from known causes (including a car accident, drowning, pneumonia, and unsuspected congenital heart disease), and five who died in the hospital with chronic conditions causing hypoxia-ischemia.&lt;/p&gt;
&lt;p&gt;SIDS cases had mean serotonin levels of 31.4 pmol/mg of protein in the paragigantocellularis lateralis, compared with 40.0 pmol/mg among the controls who died acutely (&lt;em&gt;P&lt;/em&gt;=0.04).&lt;/p&gt;
&lt;p&gt;Levels averaged 55.4 versus 75.5 pmol/mg of protein, respectively, in the raph&amp;#233; obscurus (&lt;em&gt;P&lt;/em&gt;=0.05).&lt;/p&gt;
&lt;p&gt;These abnormalities in the medulla did not appear to involve the catecholamine system. Catecholamine levels were similar between SIDS cases and controls.&lt;/p&gt;
&lt;p&gt;Nor was there evidence for excessive degradation of dopamine or neurotransmitter turnover in SIDS cases, supporting the idea that the key abnormality is reduced synthesis of serotonin, the researchers said.&lt;/p&gt;
&lt;p&gt;Another marker of serotonin function  --  tryptophan hydroxylase (TPH2), the key enzyme involved in synthesis of serotonin  --  also supported this conclusion, with 22% lower levels in the raph&amp;#233; obscurus in SIDS than in controls (&lt;em&gt;P&lt;/em&gt;=0.03).&lt;/p&gt;
&lt;p&gt;Serotonin receptor binding was 29% to 55% lower in three medullary nuclei that receive serotonin projections, notable for a decrease in binding with older age in SIDS cases, but not controls, the researchers noted.&lt;/p&gt;
&lt;p&gt;Given similar findings in three previous investigations, this &quot;may reflect a progressive decrease with age in those infants with the &apos;SIDS abnormality,&apos;&quot; they wrote. Or it&apos;s possible that those with a &quot;stronger abnormality take longer to outgrow the risk period for SIDS and continue to die at older ages,&quot; Kinney&apos;s group wrote.&lt;/p&gt;
&lt;p&gt;Likewise, serotonin receptor binding in infants who died from SIDS was significantly lower in those without known risk factors for SIDS, such as &lt;a href=&quot;http://www.medpagetoday.com/Pediatrics/GeneralPediatrics/17365&quot; mce_href=&quot;http://www.medpagetoday.com/Pediatrics/GeneralPediatrics/17365&quot; target=&quot;_blank&quot;&gt;sleeping face down&lt;/a&gt;, &quot;suggesting that additional risk factors are necessary to precipitate death when the medullary serotonin system is less compromised,&quot; they added.&lt;/p&gt;
&lt;p&gt;Although repetitive apnea and agonal &lt;a href=&quot;http://www.medpagetoday.com/Pulmonology/SleepDisorders/2817&quot; mce_href=&quot;http://www.medpagetoday.com/Pulmonology/SleepDisorders/2817&quot; target=&quot;_blank&quot;&gt;impaired gasping&lt;/a&gt; before death have been reported in some SIDS cases, chronic impaired oxygenation in the hospitalized children in the study produced a very different serotonin pattern than that seen in SIDS.&lt;/p&gt;
&lt;p&gt;Children who died with chronic hypoxia conditions had 55% higher serotonin levels in the raph&amp;#233; obscurus (&lt;em&gt;P&lt;/em&gt;=0.02) and 126% higher levels in the paragigantocellularis lateralis (&lt;em&gt;P&lt;/em&gt;=0.002) than the SIDS cases.&lt;/p&gt;
&lt;p&gt;They also had 640% higher dopamine levels in the raph&amp;#233; obscurus than the SIDS cases (&lt;em&gt;P&lt;/em&gt;=0.006).&lt;/p&gt;
&lt;p&gt;This suggested &quot;that the primary mechanisms underlying serotonin abnormalities in SIDS are not mediated by chronic hypoxia-ischemia,&quot; Kinney&apos;s group wrote.&lt;/p&gt;
&lt;p&gt;The researchers cautioned that their neurotransmitter measurements may have been off somewhat due to prolonged postmortem intervals.&lt;/p&gt;
&lt;p&gt;They also warned that the study was limited by inability to perform these measurements at the synapse in postmortem tissues and by the small sample of controls.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by the First Candle/SIDS Alliance, CJ Martin Overseas Fellowship (National Health and Medical Research Council of Australia), CJ Murphy Foundation for Solving the Puzzle of SIDS, CJ Foundation for SIDS, National Institute of Child Health and Development, and the Developmental Disabilities Research Center at Children&apos;s Hospital Boston.&lt;/p&gt;&lt;p&gt;The researchers reported no conflicts of interest.&lt;/p&gt;&lt;p&gt;McClain provided no information on conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_353"
                     title="Helmets Linked to Reduced Head Injury Risk in Alpine Sports (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/Neurology/HeadTrauma/tb/18227?impressionId=1265799800073"
                     
      Skiers and snowboarders have a significantly lower risk of head injury if they wear helmets, a meta-analysis showed.&lt;br&gt;
&lt;br&gt;In a pooled analysis of nine studies, helmet wearers were 35% less likely to suffer a head injury than those without helmets (OR 0.65, 95% CI 0.55 to 0.79), Brent Hagel, PhD, of the University of Calgary in Alberta, and colleagues reported online in the &lt;em&gt;Canadian Medical Association Journal&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;The association was significant for skiers and snowboarders alike.&lt;br&gt;
&lt;br&gt;Although there has been some concern that use of a helmet could increase the risk of neck injury because of the extra weight it adds to the head, especially with children, the studies did not confirm any danger.&lt;/p&gt;
&lt;p&gt;&quot;Based on our findings, we encourage the use of helmets among skiers and snowboarders,&quot; the researchers wrote.&lt;/p&gt;
&lt;p&gt;Various reports have estimated that 9% to 19% of injuries that occur on the slopes are head injuries and 1% to 4% are neck injuries.&lt;/p&gt;
&lt;p&gt;Traumatic brain injury is the leading cause of death and serious injury among skiers and snowboarders.&lt;/p&gt;
&lt;p&gt;A recent example was the training accident of U.S. Olympic hopeful snowboarder Kevin Pearce, who suffered a severe traumatic brain injury when he fell and hit his head on the edge of a half pipe on New Year&apos;s Eve. He was wearing a helmet.&lt;/p&gt;
&lt;p&gt;Although injury prevention efforts in alpine activities have focused on helmets, there were no systematic reviews of their effectiveness, the new study&apos;s authors noted.&lt;/p&gt;
&lt;p&gt;So Hagel and colleagues assembled data from 10 case-control studies, one case-control/case-crossover study, and one cohort study, totalling 9,829 participants who were wearing helmets and 36,735 who weren&apos;t. The studies evaluated head injury, neck injury, or both.&lt;/p&gt;
&lt;p&gt;In addition to protecting adults from head injury, the researchers found, helmets also appeared to protect children younger than 13 (OR 0.39, 95% CI 0.23 to 0.65).&lt;/p&gt;
&lt;p&gt;While two of four studies looking at potentially severe head trauma  --  resulting in referral to an emergency physician or hospital for treatment or evacuation by ambulance  --  found a reduced risk in those wearing helmets, the other two found no effect.&lt;/p&gt;
&lt;p&gt;There was some evidence that risk of head injury was reduced for males wearing helmets, but not for females, although sex was not found to be a significant modifier of the relationship between helmet use and injury risk (&lt;em&gt;P&lt;/em&gt;=0.09).&lt;/p&gt;
&lt;p&gt;Helmet use was not associated with risk of neck injury, even among children, which &quot;is consistent with biomechanical data showing no increase in neck loads associated with helmet use in simulated snowboarding falls,&quot; the researchers noted in the journal.&lt;/p&gt;
&lt;p&gt;The meta-analysis had some limitations, they wrote, including the moderate methodologic quality of the included studies, two different approaches for determining control groups (noninjured skiers and snowboarders versus those with injuries not involving the head or neck), the inclusion of English-language studies only, and variations in confounders, definitions of head injury, and places of and personnel involved in diagnosis.&lt;/p&gt;
&lt;p&gt;In addition, the researchers were unable to examine the results in terms of the design, quality, or fit of the helmets for cases.&lt;/p&gt;
&lt;p&gt;&quot;Methodologically rigorous research is required to determine which types of helmets provide the best protection,&quot; they wrote.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;No external funding was received for the study.&lt;/p&gt;&lt;p&gt;Hagel holds the Alberta Children&apos;s Hospital Foundation Professorship in Child Health and Wellness, funded through the support of an anonymous donor and the Canadian National Railway Company. He also holds a Population Health Investigator Award from the Alberta Heritage Foundation for Medical Research and a New Investigator Award from the Canadian Institutes of Health Research.&lt;/p&gt;&lt;p&gt;One of his co-authors holds a doctoral studentship from the Alberta Heritage Foundation for Medical Research.&lt;/p&gt;&lt;p&gt;The authors reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_341"
                     title="Doctor&apos;s Orders: Brain&apos;s Wiring Makes Change Hard"
                     score="0.009"
                     href="http://www.medpagetoday.com/Psychiatry/Addictions/tb/18207?impressionId=1265799800073"
                     
      &lt;p&gt;Doctor&apos;s Orders&lt;em&gt; is a feature in the collaboration between &lt;/em&gt;MedPage Today &lt;em&gt;and&lt;/em&gt; ABC News&lt;em&gt;. In this monthly segment we explore medical issues of interest to physicians and their patients alike. This month, we look at addiction and addictive behaviors, and what neuroimaging studies have revealed about why it&apos;s so hard to break bad habits. &lt;/em&gt;&lt;/p&gt;&lt;hr&gt;

&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;

&lt;p&gt;By the end of January, many New Year&apos;s resolutions have been tossed out with the leftover holiday cookies. That&apos;s because change is hard  --  and neuroscientists are learning why.&lt;br&gt;
&lt;br&gt;Advances in neuroimaging have enabled researchers to peer inside the brains of addicts and patients with addictive behaviors. They can see in real-time what gets patients hooked: how the brain&apos;s reward system  --  based largely on the neurotransmitter dopamine  --  thirsts for more, while inhibitory control centers experience a system failure.&lt;br&gt;
&lt;br&gt;The pattern is similar across all kinds of behaviors  --  from cocaine and tobacco addiction to overeating. That&apos;s why changing your mind may be the first step toward breaking a habit, but altering the brain&apos;s neural machinery is the real challenge.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Hijacked Pathways&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Drug-taking and other addictive behaviors &quot;hijack&quot; the brain&apos;s reward system, says Petros Levounis, MD, director of the Addiction Institute of New York at St. Luke&apos;s and Roosevelt Hospitals in Manhattan.&lt;/p&gt;
&lt;p&gt;In normal patients, dopamine plays a major role in motivation and reward, surging before and during a pleasurable activity  --  say, eating or sex  --  to make patients want to repeat a behavior that&apos;s crucial to the survival of the species.&lt;/p&gt;
&lt;p&gt;Dopaminergic pathways connect the limbic system, responsible for emotion, with the hippocampus, etching rewarding behaviors into the brain by creating strong, salient memories.&lt;/p&gt;
&lt;p&gt;The problem arises when the memory and the craving to recapture it takes over a person&apos;s life.&lt;/p&gt;
&lt;p&gt;&quot;Imagine what a strong hold these hijacked reward pathways take on our brains and our whole existence when they&apos;re so closely connected, geographically and anatomically speaking, with our memories and our emotions,&quot; Levounis says.&lt;/p&gt;
&lt;p&gt;As the dopamine surge repeats and repeats, it gains speed, but the brakes begin to fail: Normal function in the brain&apos;s frontal lobes, responsible for inhibitory control and executive functioning (read: willpower), tends to decrease in addicts.&lt;/p&gt;
&lt;p&gt;&quot;Ultimately,&quot; Levounis says, &quot;the war on drugs is a war between the hijacked reward pathways that push the person to want to use, and the frontal lobes, which try to keep the beast at bay. That is the essence of addiction.&quot;&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Similar Patterns&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;These neural pathways have been well studied in the brains of hardcore addicts. Now, researchers say they see similar pathways involved in other bad behaviors.&lt;/p&gt;
&lt;p&gt;Gene-Jack Wang, MD, of Brookhaven National Laboratory on New York&apos;s Long Island, has conducted several brain imaging studies of obese patients using PET-CT scans.&lt;/p&gt;
&lt;p&gt;The scans have revealed similarities in brain activity  --  or a lack thereof  --  between patients addicted to cocaine or alcohol, and those &quot;addicted&quot; to eating. Normally, the PET scan lights up when a contrast of radioactive glucose is metabolized, revealing an area of red activity in the center of the brain.&lt;/p&gt;
&lt;p&gt;But in both drug-addicted and obese patients, the scans show very little red activity, because there aren&apos;t enough receptors to which the radioactive glucose can bind. Wang says the decreased availability of dopamine receptors is the brain&apos;s way of coping with a constant dopamine overload.&lt;/p&gt;
&lt;p&gt;&quot;If a person constantly has an excess of dopamine, the brain will down-regulate,&quot; Wang says, explaining the principle commonly referred to as tolerance. &quot;Once the system is down-regulated, we have to do more in order to get the same amount of feeling in our normal state.&quot;&lt;/p&gt;
&lt;p&gt;Thus, obese patients &quot;will want to eat more in order to compensate for their down-regulated system.&quot;&lt;/p&gt;
&lt;p&gt;In other experiments, Wang and his colleagues have also found that a higher body mass index (BMI) correlated with lower prefrontal cortex function  --  the area associated with inhibitory control.&lt;/p&gt;
&lt;p&gt;&quot;If they&apos;re obese,&quot; Wang said, &quot;they have a problem controlling their eating behaviors.&quot;&lt;/p&gt;
&lt;p&gt;Those studies also revealed that a higher BMI was linked to a decrease in memory and executive functioning.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Out of Control&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Ed Susman was 293 pounds when he decided to join a clinical trial for an investigational weight-loss drug and chronicle his year-long experience for &lt;em&gt;MedPage Today&lt;/em&gt;. (See &lt;a href=&quot;http://www.medpagetoday.com/PrimaryCare/Diabetes/8125&quot; mce_href=&quot;http://www.medpagetoday.com/PrimaryCare/Diabetes/8125&quot; target=&quot;_blank&quot;&gt;Journalist Participant to Present Insider View of Weight-Loss Trial&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Eating, to him, was a &quot;compulsion&quot;  --  as was biting his nails, a habit he picked up at age 4.&lt;/p&gt;
&lt;p&gt;Over the course of the trial, not only did Susman lose 52 pounds, he also stopped his nail-biting.&lt;/p&gt;
&lt;p&gt;He doesn&apos;t yet know if he was in the drug arm of the trial, but he strongly suspects he wasn&apos;t experiencing a placebo effect.&lt;/p&gt;
&lt;p&gt;&quot;I believe I was on the drug because it controlled a compulsion that I had had for 50 years,&quot; Susman says of the nail-biting. &quot;This stopped it cold.&quot;&lt;/p&gt;
&lt;p&gt;Unfortunately, he says, the same didn&apos;t happen with his eating habits, but he&apos;s gained back only 10 of those 52 pounds in the year since his participation in the trial ended.&lt;/p&gt;
&lt;p&gt;The still-investigational drug is lorcaserin  --  a combination of benzazepine and hydrochloride, two neurological agents. Susman says it is &quot;supposed to improve your willpower, your ability to overcome compulsions.&quot;&lt;/p&gt;
&lt;p&gt;Lorcaserin is a selective 5-HT&lt;sub&gt;2C&lt;/sub&gt; receptor agonist, working through the serotonin system, which regulates appetite, mood, and motor behavior.&lt;/p&gt;
&lt;p&gt;Two other investigational obesity drugs target the dopamine reward system  --  Contrave, which is a combination of bupropion and naltrexone, and Qnexa, which combines phentermine and topiramate.&lt;/p&gt;
&lt;p&gt;&quot;Some medications that have used similar dopamine modulation, until now, have failed,&quot; Wang said. &quot;These two companies are using the command of the modulation of the dopamine system with other neurological systems, such as the opiate or norepinephrine system. According to the trials, they&apos;ve been very effective.&quot;&lt;/p&gt;
&lt;p&gt;Wang called the new medications &quot;a bright light for the treatment of obesity.&quot;&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Kicking the Habit&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Basically, the idea of medications that act on the dopamine system is &quot;to cool down those reward pathways,&quot; Levounis says. There are two strategies for doing so: an agonist strategy, or an antagonist strategy.&lt;/p&gt;
&lt;p&gt;The agonist strategy is &quot;feeding the beast, providing activity in the cell so that the cravings go down,&quot; Levounis said. Classic examples are nicotine patches, or methadone for opioid dependence.&lt;/p&gt;
&lt;p&gt;On the other hand, the antagonist strategy is to block the receptors. Naltrexone, for example, will block opioid receptors so that the drug addict won&apos;t feel anything if he or she attempts to get high.&lt;/p&gt;
&lt;p&gt;&quot;After a while, you say, &apos;This is not worth my time, my money, my trouble,&apos; so you stop using,&quot; Levounis explains.&lt;/p&gt;
&lt;p&gt;These have been the two main strategies in addiction pharmacotherapy, but there&apos;s now a &quot;third avenue&quot;  --  the partial agonist approach.&lt;/p&gt;
&lt;p&gt;The partial agonist is one molecule that blocks most receptors while still providing just a little bit of an &quot;oomph&quot; to calm cravings. That&apos;s how varenicline (Chantix) helps smokers quit, and how buprenorphine gets junkies off heroin or other opioids.&lt;/p&gt;
&lt;p&gt;But what about inhibitory control? What if medications could ramp up will power?&lt;/p&gt;
&lt;p&gt;&quot;It&apos;s an area of active research,&quot; Levounis says. &quot;There are some medications proposed, but nothing to write home about.&quot;&lt;/p&gt;
&lt;p&gt;He said treatment is typically twofold. For addicts, psychiatrists will try to &quot;cool down&quot; the reward pathways, often with medication. Then, they target the diminished frontal lobes.&lt;/p&gt;
&lt;p&gt;&quot;We try to beef up the frontal lobes as much as we can, and we do that with psychotherapy,&quot; Levounis said.&lt;/p&gt;
&lt;p&gt;Researchers agree that psychotherapy is key to regaining self-control, and it&apos;s the predominant treatment used in patients with addictive behaviors.&lt;/p&gt;
&lt;p&gt;Mark Smaller, PhD, a psychoanalyst in private practice in Chicago, said psychotherapy often reveals an underlying cause for an addiction or compulsive behavior. Usually, it&apos;s anxiety or depression.&lt;/p&gt;
&lt;p&gt;Acknowledging those problems may help change behaviors. Once they&apos;re realized, a patient can start working against them, with the help of the brain&apos;s own neuroplasticity. Essentially, neurons can disconnect and reconnect, or loosen their connections and tighten them, which often manifests in noticeable change.&lt;/p&gt;
&lt;p&gt;&quot;[Psychological] insights can actually begin to change brain chemistry and diffuse compulsions,&quot; he said. &quot;If you address those issues, you can have a positive impact on your life that can change the chemistry of your brain.&quot;&lt;/p&gt;
&lt;p&gt;Smaller said it &quot;creates a new psychological  --  if not neurological  --  structure that can help regulate behavior.&quot;&lt;/p&gt;
&lt;p&gt;Although research on neuroplasticity is relatively young, the concept of &quot;rewiring&quot; the brain is not new.&lt;/p&gt;
&lt;p&gt;In fact, too often, the electrician metaphor has been employed as an excuse for indulging, an explanation for a New Year&apos;s resolution deferred: &quot;I can&apos;t stop eating chocolate, I&apos;m just not wired that way.&quot;&lt;/p&gt;

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