Christina Kwasnica, MD Medical Director, Neurorehabilitation Barrow Neurological Institute Lisa A. Lombard, MD Medical Director, Rehabilitation Hospital of Indiana Assistant Professor Indiana University School of Medicine Dr. Kwasnica: Ipsen Speaker’s Board Dr. Lombard: none To identify and review the most clinically significant articles in CNS rehabilitation from 7/1/2014 through 6/30/2015 Each presenter selected 13-15 articles of interest from a selection of journals The preliminary lists were exchanged and a final list of 10 articles were narrowed down in areas of Spinal Cord Injury, Traumatic Brain Injury, Stroke and other neurologic conditions American Journal of Neuroradiology American Journal of Sports Medicine Annals of Emergency Medicine Archives of Neurology Brain Brain Injury International Journal of Stroke: Official Journal of the International Stroke Society Journal of the American Heart Association JAMA Journal of Neuroengineering and Rehabilitation Journal of Neurology Journal of Neurology, Neurosurgery, and Psychiatry The Journal of Neuroscience: The official journal of the Society for Neuroscience Journal of Neurotrauma The Journal of Spinal Cord Medicine Neuropharmacology Neuropsychological Rehabilitation NEJM PMR: the journal of injury, function and rehabilitation Spinal Cord Stroke: a journal of cerebral circulation Divergent long-term consequences of chronic treatment with haloperidol, risperidone, and bromocriptine on traumatic brain injury-induced cognitive deficits Many TBI patients receive antipsychotic drugs (APDs) for treatment of agitation and aggression Typical APDs, like haloperidol, can cause extrapyramidal symptoms Atypical APDs have reduced extrapyramidal symptoms but long-term affects on TBI are not clear Haloperidol has shown to delay motor recovery after brain injury both with acute or chronic treatment Both haloperidol and risperidone have been to shown to delay motor and cognitive recovery in rats with TBI • Deficits noted to be present at least 3 days after discontinuation of treatment Purpose: to assess the long term persistence of negative effects of APDs after chronic administration Methods: • 60 male adult rats used • 40 underwent controlled cortical impact injury (CCI), 20 sham procedures Treatment • 10 CCI rats per group, 5 sham, treated with 19 days of clinically significant doses of Haldoperidol 0.5 mg/kg Risperidone 0.45 mg/kg Bromocriptine 5.0 mg/kg Vehicle Motor performance was tested by beam balance and beam walking tasks • Tested at baseline on day of surgery, and then 3 trials per day on PO days 1-5 then days 48 and 108 Cognitive function was tested with a Morris Water maze task • Spatial learning began PO day 14 with 4 daily trials for 5 consecutive days, then days 48 and 108 After PO day 109, cortical lesion volume was measured One TBI+Vehicle rat was eliminated due to inability to view the MWM platform, suggestive of visual deficits Results: Beam balance • All TBI groups were impaired but no significant differences were noted on any time point Results: Beam walking • Single day analysis indicated worsening deficit in the haloperidol group on day 5 compared to bromocriptine and vehicle, but not overall on all days Results: Morris Water Maze • All TBI groups were impaired compared to sham • The haloperidol and risperidone groups were significantly impaired in comparison to the vehicle groups • On day 48 haloperidol and risperidone groups continued to be more significantly impaired • On day 108, the deficits with the haloperidol group persisted • The bromocriptine group was significantly faster than the haloperidol group Results: Lesion volume • Significantly smaller in the bromocriptine group Summary • Minimal group differences seen in motor recovery (beam balance and walk) • Spatial learning was significantly impaired in the haldoperidol and risperidone both during the treatment phase and 1 month afterwards Depression of learning continued in haloperidol group at 3 months • Bromocriptine treatment resulted in reduced cortical volume loss and improved cognitive recovery in comparison with APD treatment and vehicle Why is this important to physiatrists? • Continues to demonstrate the importance of avoiding typical and some atypical APDs • Treatment in acute care with APDs may result in slowed recovery in rehabilitation More involvement in acute care consultation may result in avoiding use of these medications • Dopaminergic medications can be helpful in recovery of TBIs A randomized trial of functional electrical stimulation for walking in incomplete spinal cord injury: Effects on walking competency Largest amount of recovery from SCI has been noted to occur in the first 6 months after SCI Rate plateaus at 12-18 months Investigations into modalities for improving function in chronic incomplete SCI • Body weight support treadmill training (BWSTT) has shown to improve gait and balance in incomplete SCI Functional electrical stimulation (FES) has been shown to improve voluntary walking function in incomplete SCI Suggested that it enhances the spinal and supraspinal neuroplasticity Majority of research has been on foot drop Previous pilot study found a multichannel FES setup can mimic a natural gait cycle over ground Study purpose to use the multichannel FES in larger population as locomotion therapy Assess if FES ambulation would reduce the secondary health complications in chronic SCI • Spasticity, muscle atrophy, bone loss Design: parallel group randomized controlled trial Subjects: Traumatic incomplete (AIS C or D) SCI C2-T12, at least 18 months after injury • Either not walking at baseline or walking with AD at a rate less than 0.5 m/s Both control and intervention groups received the same volume of therapies • 45 minute sessions, 3 days per week for 16 weeks Control group: Individually tailored exercise program • 20-25 minutes of resistance training (hand weights, cables, Uppertone training system) • 20-25 minutes of aerobic training (arm cycling, leg cycling, walking in parallel bars or treadmill) • Exercise was performed on a moderate pace Borg rating 3-5 Intervention group: FES training • 4 channel FES: B quadraceps, hamstrings, dorsiflexors and plantarflexors – pushbutton system to initiate the leg movement • Ambulated on body supported treadmill and harness system • Initially therapists controlled the pushbutton system, as the training progressed, the subject took control Intervention group: FES training • Minimal weight on the harness was used to facilitate walking • Speed was chosen to attain natural walking and which the subject could tolerate • Manual assist with leg movement was performed by therapists when needed • Subjects would have 4-5 minute bouts of walking alternating with resting intervals Outcome measures: • Gait 6 minute walk test 10 meter walk test Assistive device score Walking mobility score • Balance and mobility Timed up and go Outcome measures: • Functional measures: Spinal cord independence measure FIM locomotor score • Spasticity Modified Ashworth Pendulum test FES group SCIM mobility subscore was improved compared with the exercise group All other measures did not show significant improvement over the exercise group Both interventions resulted in improvements • 2 minute walking distances • 4 minute walking distances • 6 minute walking distance • Timed up and go Improvements persisted over time Persons with chronic incomplete SCI have potential to improve long after injury Emphases the need for continued rehabilitation in this population Authors suggest larger more homogenous population in future studies Why is this important to physiatrists? • Importance of continuing rehabilitation long after incomplete SCI to improve function • Does not necessarily require specialized equipment Liu N, Cadilhac DA, Andrew NE, Zeng L, Li Z, Li J, Li Y, Yu X, Mi B, Li Z, Xu H, Chen Y, Wang J, Yao W, Li K, Yan F, Wang J. Stroke 2014; 45:3502-3507 >30% of strokes in China are ICH Associated with poorer functional outcome and higher fatality than ischemic stroke Recent research has shown early rehabilitation in strokes may be beneficial • Improved motor recovery, reduced disability, improved quality of life • Studies limited to only small numbers of ICH ICH strokes will have different acute care management than ischemic • More stringent blood pressure management, may result in reluctance to rehabilitate early • General consensus of delayed mobilization in ICH despite no research to support it Study aim: Compare very early rehabilitation (VER – within 48 hours of ICH) with standard care Hypothesis: VER will result in lowered mortality, morbidity, and improved quality of life at 3 and 6 months after stroke Design: prospective, multicenter, randomized controlled study 2 parallel groups Eligibility: • Patients presenting <48 hours after first ICH • No contraindications to early mobilization • Fugl-Meyer score between 27-90 Exclusion criteria: • Very mild deficits • Severe aphasia or cognitive deficits • Other medical conditions such as severe CHF, LE disorders that limit mobility • Those unable to provide consent In China, families are educated to provide the rehabilitation care for both exercise, ADLs, functional training Subjects were randomized to one of 2 interventions: • Standard care: rehabilitation started 1 week after stroke • VER: rehabilitation started within 48 hours of stroke Outcome measures: • Primary: mortality at 6 months after stroke • Secondary: Questionnaires at 3 and 6 months, which included: Short Form-36 (SF-36) – health related QOL measure Modified Barthel Index – functional measure for ADLS Zung Self-rated Anxiety Scale Recurrent stroke Needed >170 patients to power the study properly No significant demographic differences between the groups Average hospital stay 10 days less in VER group (24 vs 34 days, p<0.001) Reports of experiencing adverse events in the 6 months after stroke was significantly higher in the standard treatment group (83 % vs 31 %, p<0.001) Patients in standard treatment we much less likely to be alive at 6 months No significant differences were seen in short term improvements (0-3 months) Significant improvements seen for VER group over standard care at 6 months in • Physical component summary score • Mental component summary score • Self rating anxiety scale Results summary - VER group • Shorter acute care LOS • At 6 months: More likely to be alive Greater improved QOL Independence in ADLs Improved mental health Results similar to other studies on early mobilization after stroke Possibility that families in VER group were less likely to view the patient in a dependent role and encouraged more functional independence Why is this important to physiatrists? • Continues to support early mobilization in acute stroke patients, no matter what the type of stroke • Early consultation with physiatry allows for advocating aggressive treatment and better outcomes Tiftik T, Gökkaya NKO, Malas FÜ, Tunç H, Yalçin S, Erden R, Akkus S. Spinal Cord 2015;53:467470 Persons with SCI experience a decrease in lung volume due to decreased chest wall and lung compliance, weakness in abdominal muscles, rib cage stiffness Results in ineffective cough and inability to completely clear mucous Cervical SCI may result in increased secretions, bronchospasms and pulmonary edema Pulmonary issues one of the most common causes of morbidity and mortality Locomotor training (LT) has been shown to improve cardiopulmonary function, body composition and quality of life Limited research on locomotor training on pulmonary function Small studies found reduced ventilatory demand and improved locomotorrespiratory coupling during walking Study aim • To compare the effects of LT and standard rehabilitation with rehabilitation only on pulmonary function in SCI patients Participants: 52 patients (40 male) admitted to an inpatient rehabilitation program Exclusion: • Brain injury • Joint limitations • Severe spasticity (Ashworth grades 3 and 4) Prospective design • LT group (19 men and 7 women) • Control (21 men and 5 women) Group A: received both the conventional rehabilitation program and LT Group B: conventional rehabilitation program only Conventional rehabilitation consisted of ROM and stretching exercises, balance endurance, gait training with orthoses, occupational therapy LT consisted of Body Weight Supported Treadmill Training (BWSTT) three 30 minute sessions per week for 4 weeks • Speed as low as 1 km/hr increased up to 1.5 km/hr as tolerated by the subject Resting pulmonary function was assessed before and after the rehabilitation program • • • • • • • Forced vital capacity (FVC) Forced expiratory volume in 1 second (FEV1) Forced expiratory flow rate 25-50 % (FEF 25-75) Peak expiratory flow rate (PEF) Vital capacity (VC) Ratio of FEV1 to FVC Maximum voluntary ventilation (MVV) Statistically significant improvements in VC and FVC in LT group for all injury levels and severities FVC, FEV1, FEF 25-75, VC increased significantly in LT group and no improvement in control group Mechanism of improvement not clear • LT may enhance corticospinal connectivity to LE muscles in incomplete SCI • Volitional effort may improve diaphragm and abdominal muscle activation by postural changes • LT providing increased proprioceptive input to the spinal cord Why is this important for physiatrists? • Engaging patients in locomotor therapies may result in improved pulmonary function • May result in fewer respiratory complications Skolnick BE, Maas AI, Narayan RK, van der Hoop RG, MacAllister T, Ward JD, Nelson NR, Stocchetti N. NEJM 2015 371(26);24672476 Wright DW, Yeatts SD, Silbergleit R, Palesch YY, Hertzberg VS, Frankel M, Goldstein FC, Caveney AF, Howlett-Smith H, Bengelink EM, Manley GT, Merck LH, Janis LS, Barsan WG. NEJM 2014 371(26):2457-2466 The secondary injury cascade offers an opportunity to intervene and reduce cell death and tissue damage Progesterone has been shown to have neuroprotective properties • Inhibition of inflammatory cytokines • Prevention of excitotoxicity • Reduction of apoptosis • Reduction of vasogenic edema 20 research groups working in 4 species and 22 different models have shown the neuroprotective effect of progesterone Two phase 2 randomized controlled clinical trials with progesterone showed clinical benefit • PROTECT I trial – 100 acute TBI, GCS 4-12 Progesterone resulted in reduction in mortality (13.0% vs 30.4%) • Chinese trial 159 patients with GCS < or =8 Reduced mortality Phase 3 trials: • Study of a Neuroprotective Agent, Progesterone, in Severe Traumatic Brain Injury (SYNAPSE) • Progesterone for the Treatment of Traumatic Brain Injury (PROTECT III) Multinational prospective double-blind parallel group trial July 2010-September 2013 Recruited from level 1 trauma centers 21 countries Total of 10,519 patients 16-70 years old were screened Inclusion • • • • • • criteria: GCS 8 or less post-resuscitation Marshall classification score of II or higher At least one reactive pupil Body weight 45-135 kg Initiation of treatment within 8 hours Clinical indication for monitoring intracranial pressure Exclusion criteria: • GCS 3 with B fixed dilated pupils • Life expectancy of <24 hours • Prolonged or uncorrectable hypoxemia • • • • (<60mmHg arterial) Hypotension at time of randomization (SBP <90) SCI Isolated EDH Pregnancy Subjects were randomized using a web based system, 1:1 in treatment or placebo group Infusion started with a loading dose of 0.71 mg/kg for 1 hr and then a continuous infusion of 0.5 mg/kg/hr for 119 hours During the first 6 days ABG, ICP, CPP, therapeutic intensity levels monitored Lab assessments on days 6 and 15 CT scan on day 6 Monitored for neurologic worsening daily through day 15 Follow up visits per planned for day 90 and day 180 after injury Primary outcome: GOS at 6 months Secondary outcomes: • • • • • • • • GOS at 3 months Mortality at 1 and 6 months GOS-E score Changes in ICP CPP Therapeutic intensity level Changes in CT findings SF 36 at 3 and 6 months Total of 1195 patients • Progesterone 591, placebo 588 96 % were followed for 6 months or died GOS score at 6 months did not differ between the groups (Odds ratio 0.96) Favorable outcome in 50.4 % in progesterone group and 50.5 % in placebo Vegetative state or death: 22.2 % in progesterone group and 22.3 % in placebo Secondary outcomes: No differences noted in any measure Double blind, placebo controlled clinical trial 49 trauma centers in the US Primary outcome at 6 months with GOS-E Secondary outcomes: DRS, adverse events Inclusion criteria: • Severe, moderate-severe or moderate TBI • Blunt mechanism • GCS 4-12 • Treatment initiated within 4 hours of surgery Exclusion criteria: • Nonsurvivable injury, B fixed dilated pupils, CPR required, hypotension, hypoxemia, pregnancy Intervention: infusion of progesterone or placebo • 1 hour loading dose, 71 hours of maintenance infusion, 24 h infusion taper 17,681 persons screened 882 patients enrolled • Most were moderate-severe Trial stopped after 2nd interim analysis due to futility • Favorable outcomes in 51.0 % of progesterone and 55.5 % of placebo group • No difference in 6 month mortality Why another failure of a multicenter TBI trial? • Variability and complexity of TBI • Insensitivity of outcome measurement • Difficulty in classifying TBI • Difficulty in translating experimental data to TBI in humans Why is this important to physiatrists? • Be aware of the successes and failures of trials in acute rehabilitation Mucha, A, Collins, MW, Elbin, RJ, et al. Am J Sports Med. 2014 October;42(10): 2479-2486. Vestibular complaints and impairments are documented after concussion Vestibulospinal vs. vestibulo-ocular Vestibular impairments generally assessed using assessment of the vestibulospinal system BESS, SOT Provide initial data for internal consistency for a brief clinical screening tool of vestibular and ocular motor impairments Examine the predictive validity of discriminating concussed athletes from controls 9 7 9 8 100 consecutive patients with diagnosed with sportrelated concussion- 64 met enrollment criteria as well as 78 healthy controls MeasuresVOMS PCSS Evaluated differences between patient and control groups using Mann-Whitney U test and Chi square test Used Cronbach analysis to examine internal consistency of the VOMS Logistic regression analysis to examine predictive validity of the VOMS to discriminate between concussed patients and controls Internal consistency of the VOMS total symptom score and the NPC distance is high VOR item associated with highest percentage of symptom provocation Mean NPC distance significantly greater in concussed group compared with controls Best subset of independent predictors of concussions is VMS and convergence distance VOMS has good internal consistency and basic validity with PCSS Each of the VOMS item was positively correlated with total PCSS score at a moderate level- but may not measure the same thing- NPC distance correlated at a lower level Common concussion assessment tools (SAC, BESS, SCAT-3) do not include measures of vestibular or ocular motor function May be a portion of side line and first clinic evaluation for athletes with concussion NPC distance may explain common symptoms such as difficulty reading, difficulty in focusing and blurred vision English, C, Bernhardt, J, Crotty, M, Esterman, A, Segal, L, and Hillier, S. I Jnl Stroke Vol 10, June 2015, 594-602. Providing therapy in group circuit classes will lead to improved walking ability when compared with usual care (5 days a week) Providing seven day a week therapy will lead to improved walking ability when compared with usual care Providing group circuit classes will be superior to seven day a week therapy Participants with stroke admitted to inpatient rehabilitation with moderate disability (FIM 40-80) From rehab admission to randomization received usual care After randomization received the allocated model of therapy delivery until discharge Usual care included 5 day a week therapy with a combination of individual and groups (not to exceed 4 times a week) Seven day week therapy- Received therapy on Saturday and Sunday but otherwise same as usual care. Circuit class therapy- Up for 3 hours a day with two 90 minute sessions • Ratio of 1 staff to 3 participants • Task specific activities focused on repetition 107 Six minute walk test Walking speed over 5 meters in beginning of walk test Degree of independence in walking (FAC) Degree of independence in ADLs (FIM) Wolf Motor Function test Self reported physical function Length of hospital stay Health related quality of life Resource utilization 10 8 At 4 weeks, no significant differences between groups in 6 minute walk test, walking speed, independence in walking, arm function or quality of life Length of stay did not differ significantly between groups though participants in 7 day arm had a mean 2.9 days shorter length of stay and participants in the circuit class arm had a mean 9.2 days shorter length of stay Participants in all three groups walked significantly further on the six minute walk test. Despite the substantial increase in therapy time (extra 22 hours over 4 weeks for circuit class group) there was no difference in walking ability, arm function or ADLs Content of therapy sessions (videotape analysis was done) may be as important as amount of practice Challenge of the semi-supervised nature of circuit class group and influence in activities given to patients that can be done safely Need to look at cost-effectiveness of therapy delivery models and potential that more doesn’t always mean better outcomes Role of therapy delivery methods in length of stay (median vs. mean LOS, FIM efficiency) Abo, M, Kakuda, W, Momosaki, R et al Intl J Stroke Vol. 9, July 2014, 607-612. To compare the clinical efficacy of low-frequency repetitive transcranial magnetic stimulation with intensive occupational therapy (NEURO) with constraint-induced movement therapy Recruited 66 post-stroke patients with upper limb hemiparesis greater than 1 year after stroke Baseline measures of the Fugl-Meyer Assessment and Wolf-Motor Function test done Random allocation to NEURO group (22 sessions of 20 minutes LF rTMS, 60 minute one to one training and 60 minutes self training) or CIMT group (11 sessions of 6 hour constraint induced movement therapy with supervisors Length of intervention 15 days rTMS at the site of largest motor evoked potential in FDI OT to start within 10 minutes of application of rTMS One on one training with OT consisting of shaping and repetitive task techniques Self exercise done in another room without supervision with written instructions 115 Required to wear instrumental mitt on less impaired upper limb only during CIMT Self exercise was not encouraged All CIMT done in one on one face to face manner The Fugl Meyer score and the FAS of the WMFT increased significantly in both groups The WMFT log performance time significantly decreased in both groups There was a significantly larger increase in the FAS of the WMFT in the NEURO group compared with the CIMT No significant difference between groups on the WMFT LOG score which measures distal arm movement There were significant differences in the FMA (measures whole arm) and FAS (measures proximal arm) suggesting NEURO is superior to CIMT Did not postulate mechanism of motor recovery or use functional neuroimaging Another short duration (15 day) high intensity therapy intervention for hemiparesis after stroke Unclear the functional significance of the statistically significant difference on the FAS (because both groups had an improvement) Ripley, DL, Morey, CE, Gerber, D, et al. Brain Injury Vol 28; August 2014, 1514-1522. To determine if atomoxetine would improve attention impairment in chronic TBI patients Double blind placebo control cross over trial with placebo run in 55 participants with moderate to severe TBI as measured by GCS with post-traumatic amnesia greater than 24 hours or radiographic evidence of intracranial injury Injury greater than 12 months earlier Subjects randomized into 2 groups- drug first group and placebo first group Atomoxetine 40 mg taken twice a day at 7 am and 12 noon Randomization occurred after 2 week placebo run in with repeat baseline assessment at day 14 Assessments repeated at Day 28, Day 42 and Day 56. 12 3 Brain Inj, 2014;28(12) 1514-1522 12 4 Cognitive Drug Research (CDR) Computerized Cognitive Assessment system CDR Continuity of Attention, Quality of Episodic Memory and Speed of Memory factors were analyzed separately Stroop Color and Word Test Adult ADHD Self-report Scale Neurobehavioral Functioning Inventory Trends to improvement in performance in all measures indicating a successful placebo run in No significant treatment effect of atomoxetine vs. placebo Post-hoc analysis of neuropathology unable to be completed due to preponderance of individuals with multifocal injury Atomoxetine well tolerated- only side effects greater than placebo was dry mouth and insomnia No significant effect of atomoxetine either objectively or even subjectively on self report questionnaires Variation in neuropathology may affect efficacy of the intervention- multifocal nature may disrupt the physiological pathway of action which is the noradrenergic pathway from the locus coeruleus to the prefrontal cortex Classification system focused on neuroanatomy rather than GCS may allow for discrimination of patients to focus on pharmacologically more appropriate treatments Question the use of this medication even though it is well tolerated Need to discriminate the difference between ADHD and TBI to other practitioners, payors Bettger, JP, McCoy, L, Smith, EE et al JAHA 2015;4: 1-11. To examine the trends in discharge to post acute care (PAC) in stroke patients after the implementation of the prospective payment system for acute and PAC Retrospective analysis of clinical registry data for patients treated at Get With The Guidelines- Stroke participating hospitals Enrolled consecutive admissions with acute ischemic stroke and hemorrhagic stroke Excluded those with TIA and discharge destinations other than IRF, SNF, home with HH or home without services Discharge destination based on billing codes- 01 (home without services, 06 (home with HH), 62 (IRF), 03 (SNF) Patient sociodemographics and clinical characteristics NIHSS Inability to ambulate on Day 2 Failed dysphagia screen Compared patient and hospital characteristics for stroke patients discharged to IRF, SNF, HH and home without services using Pearson chi-square tests and chi-square rank-based group means depending on the variables Fit a logistic regression model to assess specific association of stroke severity and insurance type with disposition Also analyzed trends for each discharge group from year to year and in younger and older population (above and below 65 years of age) 13 3 Unadjusted analyses of change in discharge to PAC over 8 years showed a slight increase in discharge to PAC- greatest increase for IRF, decrease for discharge to SNF Discharge to PAC increased over time for all ranges of stroke severity Strongest patient predictor of discharge to PAC was not ambulating on second day of hospital stay Medicare patients were more likely to be discharged to PAC than no insurance or private insurance Medicare’s introduction of PPS was originally associated with reduced utilization from 1998-2002. The IRF 75% rule favored stroke patients and was being newly enforced May explain the increase in discharges to IRF in patients 65 and older during this time period 13 5 Further reinforces the important indicators for post acute care we use in consultation- ambulatory status Helps form a baseline for upcoming changes in payment systems- bundled payments