201210OctoberRIR--FINAL

REHAB IN REVIEW WWW.REHABINREVIEW.COM NEUROPATHIC PAIN AND NABILONE While most current neuropathic pain (NeP) medications act upon ion channe ls , the d iscove ry o f endocannabinoids and cannabinoid receptors has led to a new u n d e r s t a n d i n g o f p a i n pathophysiology in animal models. This study assessed the efficacy of nabilone, a CB1 receptor agonist, as an adjunct ive t reatment for neuropathic pain due to diabetic peripheral neuropathy. This single-center, parallel group, double-blind, placebo controlled trial included adults 18 to 80 years of age with diabetic peripheral neuropathy associated neuropathic pain. At baseline, the patients were screened for daily pain severity and sleep disruption severity over four weeks. The subjects were randomized to receive either a flexible dose of nabilone at 1 to 4 mg per day or a placebo. The primary efficacy outcome measure was the average daily pain score during the fifth week of the double-blind phase. Eleven of 13 subjects in the nabilone group and five of 13 in the placebo group enjoyed at least a 30% reduction in pain from baseline (p<0.05). Four of thirteen subjects in the nabilone group and one of 13 in the placebo group achieved a 50% reduction in pain. A significantly greater reduction was seen in Hospital Anxiety Depression Scores (HADS) among patients receiving nabilone, as compared to those receiving placebo (p<0.05). The evaluation of sleep using the Medical Outcomes Study Sleep Scale indicated an improvement in the overall sleep problems among those receiv ing nabi lone (p<0.05) . Medication related confusion resulted in the withdrawal of 5.4% of the subjects. Conclusion: This study of diabetic peripheral neuropathy found that nabilone, an oral cannabinoid receptor agonist, is effective in reducing pain, sleep disturbance and improving quality of life. Toth, C., et al. An Enriched Enrollment Randomized Withdrawal, Flexible Dose, Double-Blind, Placebo -Controlled, Parallel Assignment Efficacy Study of Nabilone as an Adjuvant in the Treatment of Diabetic Peripheral Neuropathic Pain. Pain. 2012, October; 153(10): 2073-2082. IN VITRO FERTILIZATION AND RELAPSE OF MULTIPLE SCLEROSIS P r e v i o u s s t u d i e s h a v e demonstrated a correlation between hormonal status and the risk of relapse in patients with multiple sclerosis (MS) after pregnancy and delivery. This study investigated the influence of in vitro fertilization (IVF) treatments on the risk of relapse in women with MS. Data for this study were obtained over an 11-year period from 13 French University Hospital databases and referring neurologists. During that time, 35 patients were identified with a diagnosis of MS, each of whom had undergone at least one IVF treatment. The mean age of these patients was 32 years at the time of onset of MS, with mean disease duration of 6.6 years. The relationship between IVF and the occurrence of MS relapse was analyzed. In this cohort, 26 relapses were noted among 19 women, in the 3 month period following the 70 IVF procedures. The relapse rate was significantly increased during the three months following IVF, as compared to the same period just prior to the treatment, and to that during a control period one year prior to IVF. The significant increase in relapse was associated with both the use of gonadotrophin releasing hormone agonists (p=0.025) and IVF failure (p=0.019). Conclusion: This study of patients with multiple sclerosis found a relationship between in vitro fertilization and the risk of subsequent relapse of multiple sclerosis. This correlation was especially true among those for whom in vitro fertilization had failed. Michel, L., et al. Increased Risk of Multiple Sclerosis Relapse After in Vi tro Fert i l izat ion. J Neurol Neurosurg Psychiatry. 2012, August; 83(8): 796-802. TISSUE PLASMINOGEN ACTIVATOR BEYOND THE THREE-HOUR TIME WINDOW Among patients with acute i s c hem ic s t rok e , t he ea r l y administration of tissue plasminogen activator (t-PA) has been found to increase the likelihood of a favorable functional outcome. The American Stroke Association and the American Heart Association have recently issued a sc ient i f ic advisory recommending the administration of t- PA up to 4.5 hours after symptom onset. This study examined the effect of later administration. This prospective, multicentered study included 53 hospitals tracking patients with acute ischemic stroke. Between 2005 and 2010, 1,070 patients received t-PA during the acute stroke hospitalization. Those receiving t-PA at three hours or less were defined as the early group, and those receiving t-PA later were defined as the late group. The main outcome was any adverse clinical outcome, including in hospital deaths, h e m o r r h a g e s a n d o t h e r complications. Of the 886 eligible patients who received t-PA, 781 received t-PA within three hours and 105 between three and six hours after symptom onset. Adverse events occurred in 16.3% of those in the early group and 14.3% of those in the late group. The Volume 20 Number 10 October 5, 2012Published by Physicians In Physical Medicine and Rehabilitation © Rehab in Review ™ Editor-in-Chief David T. Burke, M.D., M.A. Emory University, Atlanta, GA Executive Editor Randolph L. Roig, M.D. Emory University, Atlanta, GA Copy Editor Roberta Alysoun Bell, Ph.D. Emory University, Atlanta, GA Contributing Editors *J. Adam Dailey, M.D. BCM/UT Alliance, Houston, TX *Mark A. Hirsch, Ph.D. Carolinas Rehabilitation, Charlotte, NC *Naureen Sheikh, M.D. East Carolina University, Greenville, NC *Jacob Lee, D.O. Lisa Foster, M.D. Laura Jones, M.D. Patrick Nguyen, M.D. Walter Sussman, D.O. David Tran, M.D. Mikhail Zhukalin, D.O. Emory University, Atlanta, GA *Richard Chang, M.D., MPH Mount Sinai Med. Ctr., New York, NY *Christina Marciniak, M.D. Samuel Chu, M.D. Marissa Cohler, M.D. Geneva Jacobs, M.D. Zack McCormick, M.D. Maria Reese, M.D. N.W.U../R.I.C., Chicago, IL *Elizabeth Nguyen, M.D. David Woznica, M.D. NYP, Columbia-Cornell, NY, NY *Jackson Liu, M.D. Kevin Bernard, M.D. NYU/Rusk Inst. of Rehab Med, NY, NY *Alan Vo, D.O. Sinai Hospital, UMD, Baltimore, MD *Matthew Dounel, M.D., MPH SUNY Downstate, Brooklyn, NY *Kwame Asante, M.D. Temple Univ./UPenn., Philadelphia, PA *Melissa Fleming, M.D. L.P. Lai, M.D. Leroy Lindsay, M.D. Beverly Hon Pavli Demian Jennifer Soo Hoo UMDNJ/Kessler Rehab, Newark, NJ *Myrlynn Delille, M.D. Jackson Cohen, M.D. University of Miami, Miami, FL *Jessica Mack, M.D. University of Michigan, Ann Arbor, MI *Todd Beery, D.O. UPenn Health System, Phil., PA *Thiru Annaswamy, M.D. Matthew Edel, D.O. Taras Ploskanych, M.D. Justin E. Statt, D.O. UT SW Medical Center, Dallas TX *Rachel Hallmark, M.D., Ph.D. proportion of patients experiencing in hospital hemorrhage or death was similar between the two groups. The adjusted mean length of hospital stay was longer for the early group than for the late group (p<0.04). Conclusion: This study of patients admitted with acute ischemic stroke found that administration of t- PA more than three hours after symptom onset did not result in an increased risk of in hospital mortality or hemorrhage, and did not result in an increased hospital length of stay. O'Brien, E., et al. Clinical Outcomes among Stroke Patients Receiving Tissue Plasminogen Activator Therapy Beyond the Three-Hour T i m e W i n d o w . J S t r o k e Cerebrovasc Dis. 2012, October; 21 (7): 541-546. FRACTALKINE AND STROKE OUTCOME Fractalkine is a chemokine, expressed on neurons, which serves as an adhesion molecule, whose receptor is expressed by monocytes, lymphocytes, natural killer cells, macrophages and microglia. In its soluble form it serves as a chemoattractant for these cells. Mice deficient in Fractalkine have smaller infarct volumes and improved survival after middle cerebral artery occlusion. This study was designed to determine whether Fractalkine levels are associated with outcome after stroke. This longitudinal study included 85 adult patients who were hospitalized for ischemic stroke. Blood was drawn for Fractalkine and i n f l a m m a t o r y m a r k e r l e v e l assessment at baseline, and the at three, seven ,90 and 180 days after s t r ok e on s e t . C l i n i c a l an d demographic data were collected on all patients. Stroke severity was measured with the National Institutes of Health Stroke Scale (NIHSS). Patients with more severe strokes had lower plasma concentrations of Fractalkine at days one and seven. At day 180, h igher c i rcu la t ing concentrations of Fractalkine were associated with better clinical outcome. Patients with poor neurological outcome at 180 days after stroke had significantly lower levels of Fractalkine than did patients with better outcomes. However, plasma concentrations of Fractalkine early after stroke were not predictive of long-term outcome. Conclusion: This study of patients with ischemic stroke found that lower levels of Fractalkine immediately after stroke are associated with worse stroke outcome. Donahue, M., et al. Higher Plasma Fractalkine Is Associated with Better Six-Month Outcome from Ischemic Stroke. Stroke. 2012, September; 43 (9): 2300-2306. MEMANTINE PLUS VITAMIN D FOR ALZHEIMER DISEASE Patients with Alzheimer disease (AD) suffer not only decreased brain cholinergic activity, but also a glutamatergic excitotoxicity that leads to loss of synaptic plasticity and increased neuronal death. Treatment with memantine, a modulator of glutamatergic excitotoxicity, may alter plasticity and delay neuronal death. Clinical results from the use of this medication have been minimal, with some suggesting the need for combination treatment. Among the candidates to combine wi th memantine is vitamin D, a hormone with neurotrophic, anti-inflammatory, antioxidant, anti-ischemic and neuroprotective properties. This study was designed to determine whether memantine combined with vitamin D is more effective than either substance alone for improving global cognitive performance in patients with AD. The subjects included 43 patients identified from the patient database of the memory clinic of Angers University Hospital in France. All patients had a new diagnosis of AD, an absence of delirium and a prescription for memantine and/or vitamin D supplements. Memantine was given orally and titrated by 5 mg increments over four weeks to a full dose of 20 mg per day. Vitamin D supplements were given orally with a dose range of between 400 and 1,000 international units per day or between 100,000 and 200,000 international units per month. Patients were followed for changes over six months in the Mini Mental State examination (MMSE) Of the 43 patients, 41.9% received memantine alone, 39.5% received vitamin D alone and 18.6% received both. Those taking Page 2 Volume 20 Number 10October 5, 2012 memantine plus vitamin D had a mean improvement in MMSE scores of four points, while participants taking memantine alone remained stable, and those taking vitamin D alone worsened by a mean of 0.6 points. The change in MMSE scores in the combined group was greater than the change among those taking memantine alone or vitamin D alone (p=0.008, and p=0.004 respectively). Conclusion: This study of patients with Alzheimer disease found that those treated with memantine combined with vitamin D for six months demonstrated a significant and clinically relevant improvement in Mini Mental State Exam scores, with this combination more effective than taking either drug alone. Annweiler, C., et al. Effectiveness of the Combination of Memantine Plus Vitamin D on Cognition in Patients with Alzheimer Disease: A Pre- Post- Pilot Study. Cogn Behav Neurol. 2012, September; 25(3): 121-127. CHOCOLATE CONSUMPTION AND STROKE AMONG MEN P r e v i o u s s t u d i e s h a v e demonstrated that chocolate consumption is associated with a lower risk of stroke among women. This Swedish study was designed to examine the association between chocolate consumption and the risk of total stroke in men. Data were obtained from the Cohort of Swedish Men study, which began in 1997 with men 45 to 79 years of age. Questionnaires were sent, including 350 items regarding diet and lifestyle factors. Chocolate consumption was assessed using a self-administered food frequency q u e s t i o n n a i r e . C h o c o l a t e consumption, in grams, was assessed by age specific portion sizes. These data were compared with the incidence of first stroke occurring between 1998 and 2008. In addition, a meta-analysis of chocolate consumption and stroke was performed using data through January 2012. During a mean follow-up period of 10.2 years, 1,995 cases of first stroke were identified. High chocolate consumption was associated with a significantly lower risk of total stroke, with those in the highest quartile of consumption having a 17% lower risk of stroke, as compared to those in the lowest quartile, after adjusting for other risk factors. The meta-analysis revealed that the overall, relative risk of stroke for the highest versus lowest category of chocolate consumption was 0.81. Conclusion: This study of Swedish men found that those who consumed at least 62.9 g per week of chocolate had a significantly reduced risk of stroke, with a 17% reduced risk as compared to those with no chocolate consumption. Larsson, S., et al. Chocolate Consumption and Risk of Stroke: A Prospective Cohort of Men and Meta- Analysis. Neurol. 2012, September 18; 79(12): 1223-1229. LOW VITAMIN D LEVELS AND STROKE RISK Human observational studies have provided evidence that vitamin D, a hormone that regulates calcium, may be beneficial in reducing the risk of hypertension and diabetes. Studies examining vitamin D status in relation to the risk of stroke morbidity or mortality have been inconsistent. This s tudy fur ther examined the relationship between plasma 25 (OH) D levels and the risk of ischemic stroke among healthy women. Data were collected from the Nurses Health Study. From 1989 to 1990 blood samples were collected from 32,826 participants who were stroke free at the time of the blood draw. Among these, 483 incident strokes were subsequently identified. Cases and control subjects were categorized into tertiles according to the distribution of serum 25 (OH) D levels. In a separate meta-analysis, six studies were identified explicitly evaluating 25(OH) D levels in relation to incident stroke or stroke mortality. After adjusting for body mass index and physical activity, women in the lowest tertile of vitamin D had a nonsignificant increase in the risk of ischemic stroke. When adjusted for dietary lifestyle risk factors and history of chronic conditions, the risk was mildly strengthened (p=0.06). This result was mirrored by findings o f a meta-ana lys is poo l ing p r o s p e c t i v e s t u d i e s t h a t demonstrated the same inverse associations between blood 25(OH) D levels and various stroke outcomes. Conclusion: This study using data from the Nurses Health Study found a modest association between low levels of vitamin D and an elevated risk of ischemic stroke. Sun, Q., et al. 25-Hydroxy Vitamin D Levels and the Risk of Stroke: A Prospective Study and Meta- Analysis. Stroke. 2012, June; 43(6): 1470-1477. INTERMEDIATE WEIGHT HYALURONIC ACID AND OSTEOARTHRITIS Hyaluronic acid (HA) is a glycoasaminoglycan constituent of synovial fluid and cartilage matrix. Th e m o lec u l a r we ig h t an d concentration have been found to be decreased in joints with osteoarthritis (OA). While viscosupplementation with exogenous HA is an established treatment for OA, studies concerning the efficacy of this treatment have provided mixed results. Some authors h a v e s u g g e s t e d t h a t t h e heterogeneity of the molecular weight of different HA formulas may have influenced these mixed results. This study compared the effects of low molecular weight HA with an intermediate molecular weight HA for the treatment of symptoms of knee OA. This randomized, controlled, double-blind, parallel group trial included patients 50 to 80 years of age with a diagnosis of knee OA. The subjects were randomized to receive either an intermediate molecular weight HA (GO-ON) or a low molecular weight HA (Hyalgan), injected into the knee joint weekly for three consecutive weeks. The primary endpoint was the change in scores on the Western Ontario and McMaster Universities (WOMAC) Pain Subscale, with secondary endpoints including several efficacy variables. After six months, changes on the WOMAC pain subscale averaged 22.9 in the GO-ON group and 18.4 in the Hyalgan group (p=0.026). This superiority pattern was seen for the majority of the secondary endpoints, including pain and clinical response. Conclusion: This study of patients with knee osteoarthritis found that three weekly injections of intermediate molecular weight hyaluronic acid is superior in reducing Page 3 Volume 20 Number 10October 5, 2012 symptoms when compared to low molecular weight hyaluronic acid. Berenbaum, F., et al. A Randomized, Double-Blind, Controlled Trial Comparing Two Intra-Articular Hyaluronic Acid Preparat ions Differing by their Low Molecular Weight in Symptomatic Knee Osteoarthritis. Ann Rheum Dis. 2012, September; 71(9): 1454-1460. BURDEN OF CAREGIVERS OF PATIENTS IN A VEGETATIVE OR MINIMALLY CONSCIOUS STATE With medical advances, the number of patients surviving an acquired severe brain injury has gradually increased. Those in a vegetative or minimally conscious state need constant assistance, placing continuous and significant demands on caregivers. This study was designed to better understand the burden experienced by caregivers of patients with disorders of consciousness (DOCs). This observational, multicenter, cross-sectional study was conducted in Italy between June of 2009 and March of 2010. This investigation included 69 centers where patients were cared for with diagnoses of vegetative or minimally conscious state. The primary caregivers were assessed using the Caregiver Needs A s s e s s m e n t , F a m i l y S t r a i n Questionnaire, Short Form-12, State- Trait Anxiety Inventory-Y, Beck Depression Inventory, Prolonged Grief Disorder Questionnaire and the Coping Orientation to Problem Experiences. Data were obtained from 487 consecutive caregivers, including 36 caregivers of children. Over 60% of the participants spent more than three hours per day with their relatives. Most caregivers were female. The participants reported reduced leisure activities, in particular meeting friends (67.6%) and walking or riding a bicycle (50%). Data from the Beck Depression Inventory determined that 59.5% had reached the most severe level of depression. Both mental and physical health were rated as low (p<0.001 for both) compared with a normative sample. Conclusion: This study of caregivers of patients in a minimally conscious or vegetative state found specific deficits in emotional, social and economic performance, and unmet communications needs with the care team. Leonardi, M., et al. Burden and Needs of 487 Caregivers of Patients in Vegetative State and in Minimally Conscious State: Results from a National Survey. Brain Inj. 2012, September; 26(10): 1201-1210. HYALURONIC ACID VS. STEROIDS FOR SUBACROMIAL IMPINGEMENT P r e v i o u s s t u d i e s h a v e demonstrated the efficacy of both corticosteroids and hyaluronic acid as t rea tm en ts fo r s ym p tom a t ic subacromial impingement. This study compared injections combining lidocaine with hyaluronic acid versus licocaine with corticosteroids for the treatment of pain associated with subacromial impingement. Subjects included 159 patients with subacromial impingement who were randomized into one of three groups for subacromial injections. Group A received a mixture of 8 mL lidocaine 1% and 2 mL hyaluronic acid. Group B received 8 mL of l idocaine 1% with 2 mL of triamcinolone