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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_425"
                     title="AAN: Industrial Cleaner Again Tied to Parkinson Risk (CME/CE)"
                     score="0.013"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAN/tb/18338?impressionId=1265773296284"
                     
      TORONTO  --  The degreasing agent trichloroethylene (TCE) has been linked to increased rates of Parkinson&apos;s disease among industrial workers in yet another study, this time involving a large, well-studied group of World War II veterans.&lt;br&gt;
&lt;br&gt;Parkinson&apos;s disease developed in individuals with occupational exposure to TCE at more than five times the rate seen in those without such exposure (odds ratio 5.5, 95% CI 1.02 to 30), reported Samuel Goldman, MD, of the Parkinson&apos;s Institute in Sunnyvale, Calif.&lt;br&gt;
&lt;br&gt;Goldman described the research in a phone interview with &lt;em&gt;MedPage Today&lt;/em&gt;. It&apos;s scheduled for presentation here in April at the American Academy of Neurology&apos;s annual meeting.&lt;br&gt;
&lt;br&gt;A previous study in 2008 had fingered TCE as the most likely culprit behind a cluster of Parkinson&apos;s disease cases afflicting workers at a single industrial plant. (See &lt;a href=&quot;http://www.medpagetoday.com/Geriatrics/ParkinsonsDisease/7894&quot; mce_href=&quot;http://www.medpagetoday.com/Geriatrics/ParkinsonsDisease/7894&quot; target=&quot;_blank&quot;&gt;Trichloroethylene Implicated as Risk for Parkinsonism&lt;/a&gt;)&lt;p&gt;&lt;/p&gt;
&lt;p&gt;Also, Goldman said, animal studies have found that TCE is selectively toxic to nigral dopaminergic neurons, the same type of nerve cell that progressively dies off in Parkinson&apos;s disease. He said the chemical&apos;s activity in rodent brains is very similar to that of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a dopaminergic neurotoxin commonly used to simulate Parkinson&apos;s disease in preclinical research.&lt;/p&gt;
&lt;p&gt;Goldman said the new study was the first population-based analysis to link TCE to the disease.&lt;/p&gt;
&lt;p&gt;It focused on 198 twin pairs in the National Academy of Sciences-National Research Council&apos;s World War II Twins Cohort, which comprises some 16,000 twin pairs overall.&lt;/p&gt;
&lt;p&gt;Members of the all-male cohort, who were born from 1917 to 1927 and served in the war, have been followed since the 1960s. Occupational histories for participants are available along with medical records from the VA healthcare system.&lt;/p&gt;
&lt;p&gt;In those pairs chosen for the current study, records showed that one twin had developed Parkinson&apos;s disease and the other had not. This design largely eliminates genetics as a confounding factor in the analysis.&lt;/p&gt;
&lt;p&gt;Goldman explained that occupational histories for each participant were reviewed by a blinded industrial hygienist and a preventive medicine physician to identify likely exposures to TCE and four other industrial chemicals: xylene, toluene, carbon tetrachloride, and tetrachloroethylene.&lt;/p&gt;
&lt;p&gt;As a single source of exposure, only TCE was significantly associated with development of Parkinson&apos;s disease, Goldman said.&lt;/p&gt;
&lt;p&gt;People working as aircraft mechanics, machinists, plumbers, and electricians likely had regular exposure to TCE, Goldman said. The chemical was commonly used as a &quot;spot&quot; cleaner to remove grease and oils from metal surfaces. It was also used for a time as a dry cleaning solvent, although tetrachloroethylene was more common for that purpose.&lt;/p&gt;
&lt;p&gt;Goldman said no increased risk was seen with xylene or toluene, but there were near-significant trends toward increased Parkinson&apos;s disease risk from carbon tetrachloride and tetrachloroethylene: &lt;ul&gt; &lt;li&gt;Carbon tetrachloride: OR 2.8 (95% CI 0.97 to 7.8)&lt;/li&gt; &lt;li&gt;Tetrachloroethylene: OR 9.0 (95% CI 0.78 to 103)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Twins exposed to either TCE or tetrachloroethylene were at significantly increased risk, with an odds ratio of 8.1 (95% CI 1.43 to 43) relative to individuals with no exposure to either chemical.&lt;/p&gt;
&lt;p&gt;Goldman said the analysis also examined whether duration of exposure was associated with increased risk. He said the results were in the same pattern as for the yes-no exposure analysis, but the findings were very uncertain because of the relatively small sample size.&lt;/p&gt;
&lt;p&gt;Occupational histories were available for only 99 of the 198 discordant twin pairs and some of the information was obtained by proxy rather than from the participant himself.&lt;/p&gt;
&lt;p&gt;Because of the wide confidence intervals even for the yes-no exposure analysis, the findings need confirmation in a larger study, he said, noting that the best approach would be a cohort study involving people with known, long-term exposure to TCE, compared with well-chosen controls.&lt;/p&gt;
&lt;p&gt;&quot;The study wouldn&apos;t have to be large,&quot; Goldman said. He estimated that 1,000 to 2,000 participants would be adequate to determine if the connection to Parkinson&apos;s disease is real.&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 the National Institute of Neurological Disorders and Stroke, the Valley Foundation, and the James and Sharron Clark Family Fund.&lt;/p&gt;&lt;p&gt;No potential conflicts of interest were reported.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_1839"
                     title="ICPDMD: Early Entacapone Doesn&apos;t Delay Dyskinesias in Parkinson&apos;s"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Neurology/ParkinsonsDisease/tb/14626?impressionId=1265773296284"
                     
      PARIS, June 9 -- Adding entacapone (Comtan) to levodopa early in Parkinson&apos;s disease does not delay onset of dyskinesias, researchers said here.
              &lt;p&gt; 
              &lt;p&gt;Instead, and contrary to expectations, early entacapone hastened onset of dyskinesias, lead author C. Warren Olanow, M.D., of Mount Sinai School of Medicine in New York, told attendees at the International Congress of Parkinson&apos;s Disease and Movement Disorders.
              &lt;p&gt; 
              &lt;p&gt;Dyskinesias develop in most Parkinson&apos;s patients after five to 10 years of successful therapy with levodopa. Evidence indicates they may be caused by pulsatile dopaminergic stimulation, Dr. Olanow said, rather than the normal continuous stimulation produced by the healthy brain.
              &lt;p&gt; 
              &lt;p&gt;There&apos;s some evidence, he said, that minimizing pulsatile stimulation may delay the onset of dyskinesias.
              &lt;p&gt; 
              &lt;p&gt;Because entacapone -- which prolongs the half-life of levodopa by inhibiting the enzyme COMT (catechol o-methyl transferase) -- is approved to reduce loss of motor function in late Parkinson&apos;s, Dr. Olanow and colleagues decided to test its use against development of dyskinesias in early disease.
              &lt;p&gt; 
              &lt;p&gt;In their study, 745 patients who required initiation of levodopa were randomized to receive either levodopa/carbidopa (LC) or levodopa/carbidopa/entacapone (LCE). (Carbidopa is dosed with levodopa to reduce nausea.)
              &lt;p&gt; 
              &lt;p&gt;Treatment continued for at least 134 weeks. The main outcome measure was time to onset of dyskinesias.
              &lt;p&gt; 
              &lt;p&gt;Dyskinesias occurred earlier in patients receiving the entacapone combination than in those receiving LC, with 42% of the entacapone patients developing them after a mean of 74 weeks compared with 32% developing them after a mean of 79 weeks in the LC group (hazard ratio 1.29, &lt;em&gt;P&lt;/em&gt;=0.038).
              &lt;p&gt; 
              &lt;p&gt;Dr. Olanow suggested that the unexpected results might by explained by differences in total levodopa exposure between the two groups.
              &lt;p&gt; 
              &lt;p&gt;Pharmacokinetic analysis showed that patients receiving the entacapone combination received significantly greater levodopa dose equivalents because of the larger area under the curve.
              &lt;p&gt; 
              &lt;p&gt;&quot;This likely accounted for these results,&quot; Dr. Olanow said.
              &lt;p&gt; 
              &lt;p&gt;&quot;There is no reason to begin entacapone in early Parkinson&apos;s disease,&quot; he said, in an attempt to delay dyskinesias. He noted that these results do not weaken the rationale for its use later in the disease.
              &lt;p&gt; 
              &lt;p&gt; 
              &lt;p&gt;&lt;table cellspacing=&quot;0&quot; hspace=&quot;1&quot; style=&quot;border-style:solid; border-width:1px; border-color:#8dabbc; font-family:arial; font-size:12px; background-color:#DBE9F2; padding:5px 5px 5px 5px;&quot;&gt;
&lt;tr&gt;&lt;td&gt;The study was funded by Novartis Pharma AG and Orion Pharma.
              &lt;p&gt;Dr. Olanow has served as a consultant for Teva Neuroscience, Novartis, and Boehringer Ingelheim and has been a member of the Scientific Advisory Board for Teva Neuroscience, Novartis, Boehringer Ingelheim, and Ceregene.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
            
    </recommendedItem>
    <recommendedItem id="20090101_19_1883"
                     title="ICPDMD: Drug Improves Symptoms in Two Dementias"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Neurology/GeneralNeurology/tb/14680?impressionId=1265773296284"
                     
      PARIS, June 12 -- Memantine (Namenda) improves symptoms in Parkinson&apos;s disease dementia and dementia with Lewy bodies, researchers said here.
              &lt;p&gt; 
              &lt;p&gt;Patients on memantine were judged significantly improved compared with those on placebo at both 12 and 24 weeks (&lt;em&gt;P&lt;/em&gt;=0.03), Dag Aarsland, M.D., of Stavanger University Hospital in Stavanger, Norway, reported at the International Congress of Parkinson&apos;s Disease and Movement Disorders.
              &lt;p&gt; 
              &lt;p&gt;Both disorders have a major impact on quality of life and treatment options are limited, Dr. Aarsland said.
              &lt;p&gt; 
              &lt;p&gt;The only approved treatment for Parkinson&apos;s disease dementia is the cholinesterase inhibitor rivastigmine, and there are no approved treatments for dementia with Lewy bodies.
              &lt;p&gt; 
              &lt;p&gt;But cholinergic side effects of rivastigmine limit its use, according to Dr. Aarsland.
              &lt;p&gt; 
              &lt;p&gt;Memantine is an NMDA glutamate receptor blocker that is approved in the U.S. for treatment of dementia in Alzheimer&apos;s disease.
              &lt;p&gt; 
              &lt;p&gt;To test its efficacy in the other two dementias, Dr. Aarsland and colleagues at four centers in Norway, Sweden, and the U.K. randomized 72 patients (40 with Parkinson&apos;s dementia, 32 with dementia with Lewy bodies) to placebo or 20 mg/day of memantine for 24 weeks. 
              &lt;p&gt; 
              &lt;p&gt;Patients were allowed concomitant treatment at stable doses of other medications, including anticholinergics, antidepressants, antipsychotics, and antiparkinson drugs, with the exception of amantadine, whose mechanism of action is similar to that of memantine.
              &lt;p&gt; 
              &lt;p&gt;The primary outcome variable was improvement on the Clinical Global Impression of Change (CGIC) at the completion of the study. The measure is a seven-point scale, with 1 representing a marked improvement, 4 no change, and 7 marked worsening. 
              &lt;p&gt; 
              &lt;p&gt;Rating physicians were instructed to include in their evaluation cognition, attention and wakefulness, psychiatric symptoms, motor symptoms, and daily functioning.
              &lt;p&gt; 
              &lt;p&gt;&quot;These patients have such a very wide variety of symptoms, all of which may be quite important for the patient, and they fluctuate a great deal,&quot; Dr. Aarsland said, allowing a comprehensive measure such as the CGIC to potentially capture more of a treatment&apos;s effect than more restricted measures of individual domains, such as cognitive tests. 
              &lt;p&gt; 
              &lt;p&gt;Secondary outcomes included the Mini-Mental State Score (MMSE) and several other cognitive measures, as well as the Unified Parkinson&apos;s Disease Rating Scale.
              &lt;p&gt; 
              &lt;p&gt;Eight patients receiving memantine and none receiving placebo were judged to have marked or moderate improvement on the CGIC scale. 
              &lt;p&gt; 
              &lt;p&gt;Mild improvement was seen in 11 memantine patients and 13 placebo patients. 
              &lt;p&gt; 
              &lt;p&gt;No change, or slight or moderate worsening was seen in 11 memantine patients and 20 placebo patients.
              &lt;p&gt; 
              &lt;p&gt;&quot;We were impressed,&quot; Dr. Aarsland said. &quot;It&apos;s quite remarkable to find that kind of effect.&quot;
              &lt;p&gt; 
              &lt;p&gt;Patients on memantine experienced a small but significant improvement in their MMSE scores as well -- from 20.1 to 21.5 (&lt;em&gt;P&lt;/em&gt;=0.02), while patients on placebo experienced an insignificant decline. The difference between the groups, however, was not significant. 
              &lt;p&gt; 
              &lt;p&gt;The MMSE improvement on memantine was equivalent to about the degree a typical patient would decline in the course of a year, Dr. Aarsland said. 
              &lt;p&gt; 
              &lt;p&gt;There were no significant differences between the two treatments on other secondary outcome measures. 
              &lt;p&gt; 
              &lt;p&gt;Adverse events caused 19 patients to withdraw from the study, but they were equally distributed between placebo and active treatment groups. 
              &lt;p&gt; 
              &lt;p&gt;There were no treatment-emergent adverse effects attributable to memantine, and there was no difference in the dropout rate between the two groups, &quot;which you would not see with rivastigmine,&quot; Dr. Aarsland said.
              &lt;p&gt; 
              &lt;p&gt;A larger multicenter trial is underway. 
              &lt;p&gt; 
              &lt;p&gt;Parkinson&apos;s disease dementia and dementia with Lewy bodies are thought to be related diseases on a spectrum. 
              &lt;p&gt; 
              &lt;p&gt;When dementia follows parkinsonian signs by more than two years, Parkinson&apos;s disease dementia is the usual diagnosis. When dementia symptoms develop before that in the context of parkinsonian signs, dementia with Lewy bodies is more often the diagnosis.
              &lt;p&gt; 
              &lt;p&gt;&lt;table cellspacing=&quot;0&quot; hspace=&quot;1&quot; style=&quot;border-style:solid; border-width:1px; border-color:#8dabbc; font-family:arial; font-size:12px; background-color:#DBE9F2; padding:5px 5px 5px 5px;&quot;&gt;
&lt;tr&gt;&lt;td&gt;Dr. Aarsland disclosed no financial conflicts.
              &lt;p&gt; 
              &lt;p&gt;The study was funded by H Lundbeck A/S.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
            
    </recommendedItem>
    <recommendedItem id="20100101_19_85"
                     title="PET Imaging Ups Diagnostic Accuracy in Parkinson&apos;s (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Neurology/ParkinsonsDisease/tb/17875?impressionId=1265773296284"
                     
      Metabolic brain imaging improved diagnostic accuracy by about 20% in patients with features of early parkinsonism but an uncertain clinical diagnosis, international researchers reported.&lt;br&gt;
&lt;br&gt;Writing online in &lt;em&gt;Lancet Neurology&lt;/em&gt;, Chris Tang, MD, of the Feinstein Institute for Medical Research in Manhasset, N.Y., and colleagues reported that image-based classification for idiopathic Parkinson&apos;s disease had 84% sensitivity, 97% specificity, 98% positive predictive value, and 82% negative predictive value.&lt;br&gt;
&lt;br&gt;In comparison to these high values, published clinicopathologic data suggest that the positive predictive value of a clinical diagnosis, even by a specialist, is only about 75%.&lt;/p&gt;
&lt;p&gt;Many neurodegenerative diseases share common signs and symptoms, and some 80% of patients misdiagnosed as having Parkinson&apos;s disease actually have multiple system atrophy or progressive supranuclear palsy.&lt;/p&gt;
&lt;p&gt;These conditions have a much worse prognosis than idiopathic Parkinson&apos;s disease, which does not substantially shorten lifespan.&lt;/p&gt;
&lt;p&gt;Moreover, treatments differ for these conditions, so more accurate diagnostic techniques have been needed.&lt;/p&gt;
&lt;p&gt;So Tang and colleagues employed an imaging technique known as fluorine-18-labeled-fluorodeoxyglucose (FDG)-PET to identify specific disease-related metabolic patterns for the three conditions.&lt;/p&gt;
&lt;p&gt;They noted that Parkinson&apos;s disease was characterized by increased pallidothalamic and pontocerebellar metabolic activity. Multiple system atrophy had bilateral reductions in putamen and cerebellar activity, and supranuclear palsy showed metabolic deficits in the upper brain stem, medial frontal cortex, and medial thalamus.&lt;/p&gt;
&lt;p&gt;Among 167 patients with parkinsonian features but uncertain clinical diagnosis who underwent FDG-PET, 96 were classified as having Parkinson&apos;s disease, 41 with multiple system atrophy, and 30 with progressive supranuclear palsy.&lt;/p&gt;
&lt;p&gt;Patients also were assessed clinically by blinded movement disorders specialists and followed for a mean of 2.6 years before a final clinical diagnosis was made.&lt;/p&gt;
&lt;p&gt;The investigators employed a multiple-pattern analytical technique to compute a patient&apos;s likelihood of having each disease, and calculated the discriminative measures for each.&lt;/p&gt;
&lt;p&gt;They found that the imaging classifications were accurate not only for idiopathic Parkinson&apos;s disease, but also for multiple system atrophy: &lt;ul&gt; &lt;li&gt;Sensitivity, 85%&lt;/li&gt; &lt;li&gt;Specificity, 96%&lt;/li&gt; &lt;li&gt;Positive predictive value, 97%&lt;/li&gt; &lt;li&gt;Negative predictive value, 83%&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;And for progressive supranuclear palsy: &lt;ul&gt; &lt;li&gt;Sensitivity, 88%&lt;/li&gt; &lt;li&gt;Specificity, 94%&lt;/li&gt; &lt;li&gt;Positive predictive value, 91%&lt;/li&gt; &lt;li&gt;Negative predictive value, 92%&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;They also calculated these discriminative values for patients with short duration of disease (less than two years), when it can be particularly difficult to make a diagnosis clinically because disease-specific features have not yet appeared.&lt;/p&gt;
&lt;p&gt;Patients with short duration of disease also would be &quot;ideal participants in clinical trials of potential disease-modifying drugs,&quot; the investigators noted.&lt;/p&gt;
&lt;p&gt;Among 55 patients with short-duration disease, the positive predictive values for idiopathic Parkinson&apos;s disease and atypical parkinsonian syndrome were 92% and 95%, respectively.&lt;/p&gt;
&lt;p&gt;And among 33 of these patients who were then followed for at least two years after imaging, the positive predictive values rose to 94% and 100%.&lt;/p&gt;
&lt;p&gt;This ability to make an imaging classification accurately several years before the final clinical diagnosis &quot;is especially relevant when considering treatment options for patients with medically refractory parkinsonism because invasive surgical approaches such as deep brain stimulation are generally ineffective for patients with atypical parkinsonian syndrome,&quot; the investigators wrote.&lt;/p&gt;
&lt;p&gt;Moreover, for patients with atypical parkinsonism, the high sensitivity and specificity &quot;will be of particular advantage when assessing potential participants in clinical trials of drugs to treat these progressive disorders.&quot;&lt;/p&gt;
&lt;p&gt;An accompanying editorial noted that the different types of parkinsonism cannot be classified with available techniques such as imaging of dopamine transporters with single-photon emission CT or of fluorodopa uptake with PET.&lt;/p&gt;
&lt;p&gt;&quot;The clinical and research relevance of these findings should not be underestimated,&quot; wrote Angelo Antonini, of IRCCS San Camillo, Venice and Parkinson Institute in Milan, Italy.&lt;/p&gt;
&lt;p&gt;&quot;Neuroprotective and disease-modifying drug research is intensifying and results mostly rely on accurate early diagnosis. If neuronal loss in Parkinson&apos;s disease follows a linear or exponential pattern, early treatment is crucial,&quot; Antonini argued.&lt;/p&gt;
&lt;p&gt;But advanced imaging should not be considered a replacement for thorough clinical investigation by movement disorder neurologists, and prospective multicenter studies are needed to confirm the accuracy of this metabolic pattern-based approach, he cautioned.&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 the National Institutes of Health and General Clinical Research Center at the Feinstein Institute for Medical Research.&lt;/p&gt;&lt;p&gt;One investigator holds patents for the use of spatial patterns in the diagnosis of brain disease, but has no financial conflicts of interest.&lt;/p&gt;&lt;p&gt;The editorialist declared no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_3_506"
                     title="SFN: Parkinson&apos;s Disease Gene Transfer Called Safe"
                     score="-0.005"
                     href="