Skip to main content

Advertisement

SpringerLink
Log in

Biomarkers and Predictors of Restorative Therapy Effects After Stroke

  • Stroke (HP Adams Jr, Section Editor)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Many restorative therapies that promote brain repair are under development. Stroke is very heterogeneous, highlighting the need to identify target populations and to understand intersubject differences in treatment response. Several neuroimaging measures have shown promise as biomarkers and predictors, including measures of structure and function, in gray matter and white matter. The choice of biomarker and predictor can differ with the content of therapy and with the population under study, for example, contralesional hemisphere measures may be of particular importance in patients with more severe injury. Studies of training effects in healthy subjects provide insights useful to brain repair. Limitations of published studies include a focus on chronic stroke, however the brain is most galvanized to respond to restorative therapies in the early days after stroke. Multimodal approaches might be the most robust approach for stratifying patients and so for optimizing prescription of restorative therapies after stroke.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2–220.

    Article  PubMed  Google Scholar 

  2. Adeoye O, Hornung R, Khatri P, Kleindorfer D. Recombinant tissue-type plasminogen activator use for ischemic stroke in the United States: a doubling of treatment rates over the course of 5 years. Stroke. 2011;42(7):1952–5.

    Article  PubMed  CAS  Google Scholar 

  3. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317–29.

    Article  PubMed  CAS  Google Scholar 

  4. Dancause N, Nudo RJ. Shaping plasticity to enhance recovery after injury. Prog Brain Res. 2011;192:273–95.

    Article  PubMed  Google Scholar 

  5. Cramer SC. Repairing the human brain after stroke. II. Restorative therapies. Ann Neurol. 2008;63(5):549–60.

    Article  PubMed  Google Scholar 

  6. Volpe BT, Huerta PT, Zipse JL, et al. Robotic devices as therapeutic and diagnostic tools for stroke recovery. Arch Neurol. 2009;66(9):1086–90.

    Article  PubMed  Google Scholar 

  7. Wolf SL, Thompson PA, Winstein CJ, et al. The EXCITE stroke trial: comparing early and delayed constraint-induced movement therapy. Stroke. 2010;41(10):2309–15.

    Article  PubMed  Google Scholar 

  8. Scheidtmann K, Fries W, Muller F, Koenig E. Effect of levodopa in combination with physiotherapy on functional motor recovery after stroke: a prospective, randomised, double-blind study. Lancet. 2001;358(9284):787–90.

    Article  PubMed  CAS  Google Scholar 

  9. Restemeyer C, Weiller C, Liepert J. No effect of a levodopa single dose on motor performance and motor excitability in chronic stroke. A double-blind placebo-controlled cross-over pilot study. Restor Neurol Neurosci. 2007;25(2):143–50.

    PubMed  CAS  Google Scholar 

  10. •• Chollet F, Tardy J, Albucher JF, et al. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet Neurol. 2011;10(2):123–30. This is a landmark study which found that targeted manipulation of brain neurochemistry initiated in the early days after stroke, here with fluoxetine, can produce significant gains in long-term behavioral outcome.

    Article  PubMed  CAS  Google Scholar 

  11. Hsu WY, Cheng CH, Liao KK, et al. Effects of repetitive transcranial magnetic stimulation on motor functions in patients with stroke: a meta-analysis. Stroke. 2012;43(7):1849–57.

    Article  PubMed  Google Scholar 

  12. Corti M, Patten C, Triggs W. Repetitive transcranial magnetic stimulation of motor cortex after stroke: a focused review. Am J Phys Med Rehabil. 2012;91(3):254–70.

    Article  PubMed  Google Scholar 

  13. Allendorfer JB, Storrs JM, Szaflarski JP. Changes in white matter integrity follow excitatory rTMS treatment of post-stroke aphasia. Restor Neurol Neurosci. 2012;30(2):103–13.

    PubMed  Google Scholar 

  14. Zimerman M, Heise KF, Hoppe J, et al. Modulation of training by single-session transcranial direct current stimulation to the intact motor cortex enhances motor skill acquisition of the paretic hand. Stroke. 2012;43(8):2185–91.

    Article  PubMed  Google Scholar 

  15. Talelli P, Wallace A, Dileone M, et al. Theta burst stimulation in the rehabilitation of the upper limb: a semirandomized, placebo-controlled trial in chronic stroke patients. Neurorehabil Neural Repair. 2012;26:976–87.

    Article  PubMed  Google Scholar 

  16. Hosp JA, Luft AR. Cortical plasticity during motor learning and recovery after ischemic stroke. Neural Plast. 2011;2011:871296.

    Article  PubMed  Google Scholar 

  17. Westlake KP, Nagarajan SS. Functional connectivity in relation to motor performance and recovery after stroke. Front Syst Neurosci. 2011;5:8.

    Article  PubMed  Google Scholar 

  18. Cramer SC, Sur M, Dobkin BH, et al. Harnessing neuroplasticity for clinical applications. Brain. 2011;134(Pt 6):1591–609.

    Article  PubMed  Google Scholar 

  19. Seitz RJ, Donnan GA. Role of neuroimaging in promoting long-term recovery from ischemic stroke. J Magn Reson Imaging. 2010;32(4):756–72.

    Article  PubMed  Google Scholar 

  20. Rehme AK, Eickhoff SB, Rottschy C, et al. Activation likelihood estimation meta-analysis of motor-related neural activity after stroke. NeuroImage. 2012;59(3):2771–82.

    Article  PubMed  Google Scholar 

  21. Kantak SS, Stinear JW, Buch ER, Cohen LG. Rewiring the brain: potential role of the premotor cortex in motor control, learning, and recovery of function following brain injury. Neurorehabil Neural Repair. 2012;26(3):282–92.

    Article  PubMed  Google Scholar 

  22. Bestmann S, Swayne O, Blankenburg F, et al. The role of contralesional dorsal premotor cortex after stroke as studied with concurrent TMS-fMRI. J Neurosci. 2010;30(36):11926–37.

    Article  PubMed  CAS  Google Scholar 

  23. Calautti C, Naccarato M, Jones PS, et al. The relationship between motor deficit and hemisphere activation balance after stroke: a 3 T fMRI study. NeuroImage. 2007;34(1):322–31.

    Article  PubMed  Google Scholar 

  24. Grefkes C, Fink GR. Reorganization of cerebral networks after stroke: new insights from neuroimaging with connectivity approaches. Brain. 2011;134(Pt 5):1264–76.

    Article  PubMed  Google Scholar 

  25. Carter AR, Shulman GL, Corbetta M. Why use a connectivity-based approach to study stroke and recovery of function? NeuroImage. 2012;62:2271–80.

    Article  PubMed  Google Scholar 

  26. Rehme AK, Eickhoff SB, Wang LE, et al. Dynamic causal modeling of cortical activity from the acute to the chronic stage after stroke. NeuroImage. 2011;55(3):1147–58.

    Article  PubMed  Google Scholar 

  27. Park CH, Chang WH, Ohn SH, et al. Longitudinal changes of resting-state functional connectivity during motor recovery after stroke. Stroke. 2011;42(5):1357–62.

    Article  PubMed  Google Scholar 

  28. Jang SH. A review of diffusion tensor imaging studies on motor recovery mechanisms in stroke patients. Neurorehabilitation. 2011;28(4):345–52.

    PubMed  CAS  Google Scholar 

  29. • Schulz R, Park CH, Boudrias MH, et al. Assessing the integrity of corticospinal pathways from primary and secondary cortical motor areas after stroke. Stroke. 2012;43:2248–51. This study suggests differential contribution of white matter integrity within M1and PMd versus ventral premotor cortex and SMA on grip strength in chronic stroke.

    Article  PubMed  Google Scholar 

  30. Wang LE, Tittgemeyer M, Imperati D, et al. Degeneration of corpus callosum and recovery of motor function after stroke: a multimodal magnetic resonance imaging study. Hum Brain Mapp. 2011.

  31. Madhavan S, Krishnan C, Jayaraman A, et al. Corticospinal tract integrity correlates with knee extensor weakness in chronic stroke survivors. Clin Neurophysiol. 2011;122(8):1588–94.

    Article  PubMed  Google Scholar 

  32. Lotze M, Beutling W, Loibl M, et al. Contralesional motor cortex activation depends on ipsilesional corticospinal tract integrity in well-recovered subcortical stroke patients. Neurorehabil Neural Repair. 2012;26(6):594–603.

    Article  PubMed  Google Scholar 

  33. Hamzei F, Dettmers C, Rijntjes M, Weiller C. The effect of cortico-spinal tract damage on primary sensorimotor cortex activation after rehabilitation therapy. Exp Brain Res. 2008;190(3):329–36.

    Article  PubMed  Google Scholar 

  34. • Carter AR, Patel KR, Astafiev SV, et al. Upstream dysfunction of somatomotor functional connectivity after corticospinal damage in stroke. Neurorehabil Neural Repair. 2012;26(1):7–19. Earlier work showed a relationship between CST damage and cortical activation after stroke. This study found that CST damage also affects functional connectivity. This is important because connectivity is showing great promise as a probe of network changes after stroke.

    Article  PubMed  Google Scholar 

  35. Liepert J, Bauder H, Wolfgang HR, et al. Treatment-induced cortical reorganization after stroke in humans. Stroke. 2000;31(6):1210–6.

    Article  PubMed  CAS  Google Scholar 

  36. Sawaki L, Butler AJ, Leng X, et al. Constraint-induced movement therapy results in increased motor map area in subjects 3 to 9 months after stroke. Neurorehabil Neural Repair. 2008;22(5):505–13.

    Article  PubMed  Google Scholar 

  37. Johansen-Berg H, Dawes H, Guy C, et al. Correlation between motor improvements and altered fMRI activity after rehabilitative therapy. Brain. 2002;125(Pt 12):2731–42.

    Article  PubMed  Google Scholar 

  38. Hamzei F, Liepert J, Dettmers C, et al. Two different reorganization patterns after rehabilitative therapy: an exploratory study with fMRI and TMS. NeuroImage. 2006;31(2):710–20.

    Article  PubMed  Google Scholar 

  39. Jang SH, Kim YH, Cho SH, et al. Cortical reorganization induced by task-oriented training in chronic hemiplegic stroke patients. Neuroreport. 2003;14(1):137–41.

    Article  PubMed  Google Scholar 

  40. Dong Y, Dobkin BH, Cen SY, et al. Motor cortex activation during treatment may predict therapeutic gains in paretic hand function after stroke. Stroke. 2006;37(6):1552–5.

    Article  PubMed  Google Scholar 

  41. Takahashi CD, Der-Yeghiaian L, Le V, et al. Robot-based hand motor therapy after stroke. Brain. 2008;131(Pt 2):425–37.

    Article  PubMed  Google Scholar 

  42. Nelles G, Jentzen W, Jueptner M, et al. Arm training induced brain plasticity in stroke studied with serial positron emission tomography. NeuroImage. 2001;13(6 Pt 1):1146–54.

    Article  PubMed  CAS  Google Scholar 

  43. Luft AR, McCombe-Waller S, Whitall J, et al. Repetitive bilateral arm training and motor cortex activation in chronic stroke: a randomized controlled trial. Jama. 2004;292(15):1853–61.

    Article  PubMed  CAS  Google Scholar 

  44. Wittenberg GF, Chen R, Ishii K, et al. Constraint-induced therapy in stroke: magnetic-stimulation motor maps and cerebral activation. Neurorehabil Neural Repair. 2003;17(1):48–57.

    Article  PubMed  Google Scholar 

  45. Liepert J, Hamzei F, Weiller C. Lesion-induced and training-induced brain reorganization. Restor Neurol Neurosci. 2004;22(3–5):269–77.

    PubMed  CAS  Google Scholar 

  46. Ward N, Brown M, Thompson A, Frackowiak R. The influence of time after stroke on brain activations during a motor task. Ann Neurol. 2004;55(6):829–34.

    Article  PubMed  Google Scholar 

  47. Schaechter J, Kraft E, Hilliard T, et al. Motor recovery and cortical reorganization after constraint-induced movement therapy in stroke patients: a preliminary study. Neurorehabil Neural Repair. 2002;16(4):326–38.

    Article  PubMed  Google Scholar 

  48. • Laible M, Grieshammer S, Seidel G, et al. Association of activity changes in the primary sensory cortex with successful motor rehabilitation of the hand following stroke. Neurorehabil Neural Repair. 2012;26:881–8. This is one of the first studies to elucidate functional and behavioral relevance for a posterior shift of motor-related activation into S1 after stroke.

    Article  PubMed  Google Scholar 

  49. Schaechter JD, van Oers CA, Groisser BN, et al. Increase in sensorimotor cortex response to somatosensory stimulation over subacute poststroke period correlates with motor recovery in hemiparetic patients. Neurorehabil Neural Repair. 2012;26(4):325–34.

    Article  PubMed  Google Scholar 

  50. • Kononen M, Tarkka IM, Niskanen E, et al. Functional MRI and motor behavioral changes obtained with constraint-induced movement therapy in chronic stroke. Eur J Neurol. 2012;19(4):578–86. This study provides good evidence that, in patients with severe deficits after stroke, therapeutic intervention can improve behavioral outcome and promote neuroplasticity.

    Article  PubMed  CAS  Google Scholar 

  51. Rijntjes M, Hamzei F, Glauche V, et al. Activation changes in sensorimotor cortex during improvement due to CIMT in chronic stroke. Restor Neurol Neurosci. 2011;29(5):299–310.

    PubMed  Google Scholar 

  52. • Meehan SK, Randhawa B, Wessel B, Boyd LA. Implicit sequence-specific motor learning after subcortical stroke is associated with increased prefrontal brain activations: an fMRI study. Hum Brain Mapp. 2011;32(2):290–303. This study identifies a distributed network for learning an implicit motor task after stroke, one that differs from findings in healthy controls.

    Article  PubMed  Google Scholar 

  53. • Whitall J, Waller SM, Sorkin JD, et al. Bilateral and unilateral arm training improve motor function through differing neuroplastic mechanisms: a single-blinded randomized controlled trial. Neurorehabil Neural Repair. 2011;25(2):118–29. This is one of the first studies to study and elucidate differential functional mechanisms of improvement across two therapies.

    Article  PubMed  Google Scholar 

  54. Michielsen ME, Selles RW, van der Geest JN, et al. Motor recovery and cortical reorganization after mirror therapy in chronic stroke patients: a phase II randomized controlled trial. Neurorehabil Neural Repair. 2011;25(3):223–33.

    Article  PubMed  Google Scholar 

  55. • Nojima I, Mima T, Koganemaru S, et al. Human motor plasticity induced by mirror visual feedback. J Neurosci. 2012;32(4):1293–300. This study elucidates the plasticity mechanisms underlying behavioral improvement with mirror visual feedback, a therapy increasingly being studied as a restorative therapy after stroke.

    Article  PubMed  CAS  Google Scholar 

  56. Stagg CJ, Bachtiar V, O’Shea J, et al. Cortical activation changes underlying stimulation-induced behavioural gains in chronic stroke. Brain. 2012;135(Pt 1):276–84.

    Article  PubMed  Google Scholar 

  57. Bradnam LV, Stinear CM, Barber PA, Byblow WD. Contralesional hemisphere control of the proximal paretic upper limb following stroke. Cereb Cortex. 2011;22:2662–71.

    Article  PubMed  Google Scholar 

  58. Varkuti B, Guan C, Pan Y, et al. Resting state changes in functional connectivity correlate with movement recovery for BCI and robot-assisted upper-extremity training after stroke. Neurorehabil Neural Repair. 2012. doi:10.1177/1545968312445910.

  59. Harris-Love ML, Morton SM, Perez MA, Cohen LG. Mechanisms of short-term training-induced reaching improvement in severely hemiparetic stroke patients: a TMS study. Neurorehabil Neural Repair. 2011;25(5):398–411.

    Article  PubMed  Google Scholar 

  60. Wang LE, Fink GR, Diekhoff S, et al. Noradrenergic enhancement improves motor network connectivity in stroke patients. Ann Neurol. 2011;69(2):375–88.

    Article  PubMed  Google Scholar 

  61. • Hamzei F, Glauche V, Schwarzwald R, May A. Dynamic gray matter changes within cortex and striatum after short motor skill training are associated with their increased functional interaction. NeuroImage. 2012;59(4):3364–72. Recent studies have observed structural changes in the brain with learning and training. This is an important study describing the link between structural and functional changes in the motor system with motor skill training.

    Article  PubMed  Google Scholar 

  62. Scholz J, Klein MC, Behrens TE, Johansen-Berg H. Training induces changes in white-matter architecture. Nat Neurosci. 2009;12(11):1370–1.

    Article  PubMed  CAS  Google Scholar 

  63. Keller TA, Just MA. Altering cortical connectivity: remediation-induced changes in the white matter of poor readers. Neuron. 2009;64(5):624–31.

    Article  PubMed  CAS  Google Scholar 

  64. Halwani GF, Loui P, Ruber T, Schlaug G. Effects of practice and experience on the arcuate fasciculus: comparing singers, instrumentalists, and non-musicians. Front Psychol. 2011;2:156.

    Article  PubMed  Google Scholar 

  65. Schlaug G, Marchina S, Norton A. Evidence for plasticity in white-matter tracts of patients with chronic Broca’s aphasia undergoing intense intonation-based speech therapy. Ann N Y Acad Sci. 2009;1169:385–94.

    Article  PubMed  Google Scholar 

  66. Venkatakrishnan A, Sandrini M. Combining transcranial direct current stimulation and neuroimaging: novel insights in understanding neuroplasticity. J Neurophysiol. 2012;107(1):1–4.

    Article  PubMed  Google Scholar 

  67. Gauthier LV, Taub E, Perkins C, et al. Remodeling the brain: plastic structural brain changes produced by different motor therapies after stroke. Stroke. 2008;39(5):1520–5.

    Article  PubMed  Google Scholar 

  68. •• Taubert M, Draganski B, Anwander A, et al. Dynamic properties of human brain structure: learning-related changes in cortical areas and associated fiber connections. J Neurosci. 2010;30(35):11670–7. This study found rapid gray matter and white matter changes occur after two sessions of motor learning. In addition, gray matter and white matter changes colocalized. Although this study was conducted in healthy subjects, there is potential for these principles to be extended to studies of motor learning after stroke.

    Article  PubMed  CAS  Google Scholar 

  69. Milot MH, Cramer SC. Biomarkers of recovery after stroke. Curr Opin Neurol. 2008;21(6):654–9.

    Article  PubMed  Google Scholar 

  70. Jickling GC, Sharp FR. Blood biomarkers of ischemic stroke. Neurotherapeutics. 2011;8(3):349–60.

    Article  PubMed  CAS  Google Scholar 

  71. Navarro-Sobrino M, Rosell A, Hernandez-Guillamon M, et al. A large screening of angiogenesis biomarkers and their association with neurological outcome after ischemic stroke. Atherosclerosis. 2011;216(1):205–11.

    Article  PubMed  CAS  Google Scholar 

  72. •• Zatorre RJ, Fields RD, Johansen-Berg H. Plasticity in gray and white: neuroimaging changes in brain structure during learning. Nat Neurosci. 2012;15(4):528–36. This is a thorough and enjoyable review of the learning-induced structural changes observed with MRI as well as their likely cellular and molecular bases.

    Article  PubMed  CAS  Google Scholar 

  73. Johansen-Berg H. The future of functionally-related structural change assessment. NeuroImage. 2012;62(2):1293–8.

    Article  PubMed  Google Scholar 

  74. Cramer SC. Stratifying patients with stroke in trials that target brain repair. Stroke. 2010;41(10 Suppl):S114–6.

    Article  PubMed  Google Scholar 

  75. Coupar F, Pollock A, Rowe P, et al. Predictors of upper limb recovery after stroke: a systematic review and meta-analysis. Clin Rehabil. 2011;26:291–313.

    Article  PubMed  Google Scholar 

  76. Stinear C. Prediction of recovery of motor function after stroke. Lancet Neurol. 2010;9(12):1228–32.

    Article  PubMed  Google Scholar 

  77. Cramer SC, Parrish TB, Levy RM, et al. Predicting functional gains in a stroke trial. Stroke. 2007;38(7):2108–14.

    Article  PubMed  Google Scholar 

  78. Richter M, Miltner WH, Straube T. Association between therapy outcome and right-hemispheric activation in chronic aphasia. Brain. 2008;131(Pt 5):1391–401.

    PubMed  Google Scholar 

  79. Westlake KP, Hinkley LB, Bucci M, et al. Resting state alpha-band functional connectivity and recovery after stroke. Exp Neurol. 2012;237(1):160–9.

    Article  PubMed  Google Scholar 

  80. Carter AR, Astafiev SV, Lang CE, et al. Resting interhemispheric functional magnetic resonance imaging connectivity predicts performance after stroke. Ann Neurol. 2010;67(3):365–75.

    PubMed  Google Scholar 

  81. Stinear CM, Barber PA, Smale PR, et al. Functional potential in chronic stroke patients depends on corticospinal tract integrity. Brain. 2007;130(Pt 1):170–80.

    PubMed  Google Scholar 

  82. Riley JD, Le V, Der-Yeghiaian L, et al. Anatomy of stroke injury predicts gains from therapy. Stroke. 2011;42(2):421–6.

    Article  PubMed  Google Scholar 

  83. • Lindenberg R, Zhu LL, Ruber T, Schlaug G. Predicting functional motor potential in chronic stroke patients using diffusion tensor imaging. Hum Brain Mapp. 2012;33(5):1040–51. This study identified the importance of interhemispheric M1–M1 connections in predicting gains from tDCS plus physical therapy.

    Article  PubMed  Google Scholar 

  84. Globas C, Lam JM, Zhang W, et al. Mesencephalic corticospinal atrophy predicts baseline deficit but not response to unilateral or bilateral arm training in chronic stroke. Neurorehabil Neural Repair. 2011;25(1):81–7.

    Article  PubMed  Google Scholar 

  85. Gryga M, Taubert M, Dukart J, et al. Bidirectional gray matter changes after complex motor skill learning. Front Syst Neurosci. 2012;6:37.

    Article  PubMed  Google Scholar 

  86. •• Gauthier LV, Taub E, Mark VW, et al. Atrophy of spared gray matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke. Stroke. 2012;43(2):453–7. This is the first study to identify gray matter volume as a predictor of motor improvement with CIMT.

    Article  PubMed  Google Scholar 

  87. Nouri S, Cramer SC. Anatomy and physiology predict response to motor cortex stimulation after stroke. Neurology. 2011;77(11):1076–83.

    Article  PubMed  Google Scholar 

  88. Koski L, Mernar TJ, Dobkin BH. Immediate and long-term changes in corticomotor output in response to rehabilitation: correlation with functional improvements in chronic stroke. Neurorehabil Neural Repair. 2004;18(4):230–49.

    Article  PubMed  Google Scholar 

  89. Siironen J, Juvela S, Kanarek K, et al. The Met allele of the BDNF Val66Met polymorphism predicts poor outcome among survivors of aneurysmal subarachnoid hemorrhage. Stroke. 2007;38(10):2858–60.

    Article  PubMed  CAS  Google Scholar 

  90. Cramer SC, Procaccio V. Correlation between genetic polymorphisms and stroke recovery: analysis of the GAIN Americas and GAIN international studies. Eur J Neurol. 2012;19(5):718–24.

    Article  PubMed  CAS  Google Scholar 

  91. Stinear CM, Barber PA, Petoe M, et al. The PREP algorithm predicts potential for upper limb recovery after stroke. Brain. 2012;135(Pt 8):2527–35.

    Article  PubMed  Google Scholar 

  92. Biernaskie J, Chernenko G, Corbett D. Efficacy of rehabilitative experience declines with time after focal ischemic brain injury. J Neurosci. 2004;24(5):1245–54.

    Article  PubMed  CAS  Google Scholar 

  93. Chen J, Li Y, Wang L, et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke. 2001;32(4):1005–11.

    Article  PubMed  CAS  Google Scholar 

  94. Ren J, Kaplan P, Charette M, et al. Time window of intracisternal osteogenic protein-1 in enhancing functional recovery after stroke. Neuropharmacology. 2000;39(5):860–5.

    Article  PubMed  CAS  Google Scholar 

  95. Hodics T, Cohen LG, Cramer SC. Functional imaging of intervention effects in stroke motor rehabilitation. Arch Phys Med Rehabil. 2006;87(12 Suppl 2):S36–42.

    Article  PubMed  Google Scholar 

  96. • Sterr A, Conforto AB. Plasticity of adult sensorimotor system in severe brain infarcts: challenges and opportunities. Neural Plast. 2012;2012:970136. This review summarizes some of the plasticity and behavioral differences in more severely injured and impaired patients. Considering more patients are surviving the acute stroke phase, it highlights the need for new ways of thinking and important considerations for this population.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants R01 NS059909 and NIH/NCRR UL1TR000153.

Disclosure

E. Burke: none; S.C. Cramer: consultant to GlaxoSmithKline, Pfizer, and Microtransponder.

Author information

Authors and Affiliations

  1. Department of Anatomy & Neurobiology, University of California, Irvine, CA, USA

    Erin Burke & Steven C. Cramer

  2. Department of Neurology, University of California, Irvine, CA, USA

    Steven C. Cramer

  3. University of California, Irvine Medical Center, 101 The City Drive South, Building 53 Room 203, Orange, CA, 92868-4280, USA

    Steven C. Cramer

Authors
  1. Erin Burke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Steven C. Cramer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Steven C. Cramer.

Additional information

This article is part of the Topical Collection on Stroke

Rights and permissions

Reprints and permissions

About this article

Cite this article

Burke, E., Cramer, S.C. Biomarkers and Predictors of Restorative Therapy Effects After Stroke. Curr Neurol Neurosci Rep 13, 329 (2013). https://doi.org/10.1007/s11910-012-0329-9

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11910-012-0329-9

Keywords

Search

Navigation