Clinical evidences of brain plasticity in stroke patients

Giuseppe Lamola, Chiara Fanciullacci, Bruno Rossi, Carmelo Chisari


Emerging findings deriving from neuromodulation and neuroradiology are providing us new insights about plas- ticity and functional reorganization of the brain after stroke, but the direct clinical assessment of motor function should still be considered an indispensable tool for the evaluation of the effects of plasticity in stroke patients. Recovery of motor function can be spontaneous or guided by training. Substantial functional recovery can occur spontaneously especially in the first month post-stroke. Instead, the guided recovery may take more time and may rely on a number of rehabilitation techniques which proved to be capable of stimulating cerebral plasticity. Even the time course of these processes is a decisive element. First, it is important to correlate the trends of plasticity after stroke, from the enhancement of earlier periods to the later stages, to the behavioral changes observed. Furthermore, it is crucial to distinguish recovery of function occurring through improvement of motor deficit from compensatory mechanisms, distinction that has also an effect on timing of recovery. Another relevant question is the maintenance over time of the improvements reached with the treatment, feature on which various clinical studies have been conducted in acute and chronic stroke patients. Further studies are needed to allow us to get a more precise definition of the potentiality of functional recovery and of the mechanisms underlying the recovery depending on its levels and timing. Understanding the mechanisms, the effects and the limits of neural plasticity may eventually help enhancing the recovery process in stroke patients, significantly improving the quality of life of these patients. Then, a greater attention towards the clinical implica- tions of the changes related to plasticity can be a crucial element to further improve the therapeutic options used in neurorehabilitation.


Stroke; Plasticity; Motor recovery; Neurorehabilitation; Clinical evaluations

Full Text:



Altschuler E.L., Wisdom S.B., Stone L., Foster C., Galasko D., Llewellyn D.M.E., & Ramachandran V.S. Rehabilitation of hemiparesis after stroke with a mirror. Lancet;353: 2035-2036, 1999.

Braun S.M., Beurskens A.J., Borm P.J., Schack T. & Wade D.T. The effects of mental practice in stroke rehabilitation: a systematic review. Archives of physical medicine and rehabilitation, 87(6), 842-852, 2006.

Calabresi P., Galletti F., Saggese E., Ghiglieri V. & Picconi B. Neuronal networks and synaptic plasticity in Parkinson's disease: beyond motor deficits. Parkinsonism & related disorders;13, S259-S262, 2007.

Celnik P., Webster B., Glasser D.M., & Cohen L.G. Effects of action observation on physical training after stroke. Stroke, 39(6), 1814-1820, 2008.

Chisari C., Bertolucci F., Monaco V., Venturi M., Simonella C., Micera S. & Rossi B. Robot-assisted gait training improves motor performances and modifies Motor Unit firing in post-stroke patients. European Journal of Physical and Rehabilitation Medicine, 2014.

Coupar F., Pollock A., Rowe P., Weir C. & Langhorne P. Predictors of upper limb recovery after stroke: a systematic review and meta-analysis. Clinical rehabilitation, 0269215511420305, 2011.

Cramer S.C. Repairing the human brain after stroke: I. Mechanisms of spontaneous recovery. Annals of Neurology Vol 63, Issue 3, pages 272–287, 2008.

Dayan E., Censor N., Buch E.R., Sandrini M. & Cohen L.G. Noninvasive brain stimulation: from physiology to network dynamics and back. Nature neuroscience, 16(7), 838-844, 2013.

Dohle C., Pullen J., Nakaten A., Kust J., Rietz C., Karbe H. Mirror therapy promotes recovery from severe hemiparesis: a randomized controlled trial. Neurorehabil Neural Repair.; 23:209-217, 2009.

Duncan P.W., Goldstein L.B., Matchar D., Divine G.W. & Feussner J. Measurement of motor recovery after stroke. Outcome assessment and sample size requirements. Stroke, 23(8), 1084-1089, 1992.

Favre I., Zeffiro T. A., Detante O., Krainik A., Hommel M. & Jaillard A. Upper Limb Recovery After Stroke Is Associated With Ipsilesional Primary Motor Cortical Activity A Meta-Analysis. Stroke, 45(4), 1077-1083, 2014.

Feeney D.M., Baron J.C. Diaschisis. Stroke. 17:817–830, 1986.

Frisoli A., Sotgiu E., Procopio C., Bergamasco M., Rossi B. & Chisari C. Design and implementation of a training strategy in chronic stroke with an arm robotic exoskeleton. IEEE Int Conf Rehabil Robot, 2011.

Fugl-Meyer A.R., Jaasko L., Leyman I. Olsson S. & Steglind S. The poststroke hemiplegic patient. I. A method for evaluation of physical performance. Scand J Rehabil Med 7: 13–31, 1975.

Gladstone D.J., Danells C.J. & Black S.E. The Fugl-Meyer assessment of motor recovery after stroke: a critical review of its measurement properties. Neurorehabilitation and Neural Repair, 16(3), 232-240, 2002.

Henderson A., Korner-Bitensky N. & Levin M. Virtual reality in stroke rehabilitation: a systematic review of its effectiveness for upper limb motor recovery. Topics in stroke rehabilitation, 14(2), 52-61, 2007.

Hendricks H.T., van Limbeek J., Geurts A.C., Zwarts M.J. Motor recovery after stroke: a systematic review of the literature. Arch Phys Med Rehabil; 83(11):1629-37, 2002.

Housman S.J., Scott K.M., Reinkensmeyer D.J. A Randomized Controlled Trial of Gravity-Supported, Computer-Enhanced Arm Exercise for Individuals With Severe Hemiparesis. Neurorehabilitation and Neural Repair, 2009.

Hummel F.C. & Cohen L.G. Drivers of brain plasticity. Current opinion in neurology, 18(6), 667-674, 2005.

Jørgensen H.S., Nakayama H., Raaschou H.O., Vive-Larsen J., Støier M. & Olsen T.S. Outcome and time course of recovery in stroke. Part II: Time course of recovery. The Copenhagen Stroke Study. Archives of physical medicine and rehabilitation, 76(5), 406-412, 1995.

Katrak P., Bowring G., Conroy P., Chilvers M., Poulos R. & McNeil D. Predicting upper limb recovery after stroke: the place of early shoulder and hand movement. Archives of physical medicine and rehabilitation, 79(7), 758-761, 1998.

Kiper P., Agostini M., Luque-Moreno C., Tonin P. & Turolla A. Reinforced Feedback in Virtual Environment for Rehabilitation of Upper Extremity Dysfunction after Stroke: Preliminary Data from a Randomized Controlled Trial. BioMed research international, 2014.

Kitago T., Liang J., Huang V.S., Hayes S., Simon P., Tenteromano L., Lazar R.M., Marshall R.S., Mazzoni P., Lennihan L. & Krakauer J.W. Improvement After Constraint-Induced Movement Therapy Recovery of Normal Motor Control or Task-Specific Compensation?. Neurorehabilitation and neural repair, 1545968312452631, 2012.

Koganemaru S., Mima T., Thabit M.N., Ikkaku T., Shimada K., Kanematsu M., Takahashi K., Fawi G., Takahashi R., Fukuyama H. & Domen K. Recovery of upper-limb function due to enhanced use-dependent plasticity in chronic stroke patients. Brain, awq193, 2010.

Krakauer J.W. Motor learning: its relevance to stroke recovery and neurorehabilitation. Current opinion in neurology, 19(1), 84-90, 2006.

Kwakkel G., Kollen B. & Twisk J. Impact of time on improvement of outcome after stroke. Stroke, 37(9), 2348-2353, 2006.

Levin M.F., Kleim J.A., Wolf S.L. What do motor ‘recovery’ and ‘compensation’ mean in patients following stroke? Neurorehabilitation and Neural Repair; 23:313–319, 2009.

Liao W.W., Wu C.Y., Hsieh Y.W., Lin K.C., Chang W.Y. Effects of robot-assisted upper limb rehabilitation on daily function and real-world arm activity in patients with chronic stroke: a randomized controlled trial. Clinical Rehabilitation, 2011.

Liepert J., Bauder H., Miltner W.H., Taub E. & Weiller C. Treatment-induced cortical reorganization after stroke in humans. Stroke, 31(6), 1210-1216, 2000.

Liepert J., Miltner W.H.R., Bauder H., Sommer M., Dettmers C., Taub E. & Weiller C. Motor cortex plasticity during constraint-induced movement therapy in stroke patients. Neuroscience letters, 250(1), 5-8, 1998.

Lo A.C., Guarino P.D., Richards L.G., Haselkorn J.K., Wittenberg G.F., Federman D.G., Ringer R.J., Wagner T.H., Krebs H.I., Volpe B.T., Bever C.T.Jr., Bravata D.M., Duncan P.W., Corn B.H., Maffucci A.D., Nadeau S.E., Conroy S.S., Powell J.M., Huang G.D., & Peduzzi P. Robot-assisted therapy for long-term upper-limb impairment after stroke. New England Journal of Medicine, 362(19), 1772-1783, 2010.

Lohse K.R., Hilderman C.G.E., Cheung K.L., Tatla S., Van der Loos H.M.F. Virtual reality therapy for adults post-stroke: a systematic review and meta-analysis exploring virtual environments and commercial games in therapy. PLoS ONE 9(3): e93318. doi:10.1371/journal.pone.0093318, 2014.

Masiero S., Celia A., Rosati G. & Armani M. Robotic-assisted rehabilitation of the upper limb after acute stroke. Archives of physical medicine and rehabilitation, 88(2), 142-149, 2007.

Mezzapesa D.M., Rocca M.A., Rodegher M., Comi G., & Filippi M. Functional cortical changes of the sensorimotor network are associated with clinical recovery in multiple sclerosis. Human brain mapping 29(5), 562-573, 2008.

Michielsen M.E., Selles R.W., van der Geest J.N., Eckhardt M., Yavuzer G., Stam H.J., Smits M., Ribbers G.M. & Bussmann J.B. Motor Recovery and Cortical Reorganization After Mirror Therapy in Chronic Stroke Patients A Phase II Randomized Controlled Trial. Neurorehabilitation and Neural Repair, 25(3), 223-233, 2011.

Mulder T. Motor imagery and action observation: cognitive tools for rehabilitation. Journal of neural transmission, 114(10), 1265-1278, 2007.

Mulder T., Zijlstra S., Zijlstra W., & Hochstenbach J. The role of motor imagery in learning a totally novel movement. Experimental Brain Research, 154(2), 211-217, 2004.

Nijland R.H., van Wegen E.E., Harmeling-van der Wel B.C. & Kwakkel G. Presence of Finger Extension and Shoulder Abduction Within 72 Hours After Stroke Predicts Functional Recovery Early Prediction of Functional Outcome After Stroke: The EPOS Cohort Study. Stroke, 41(4), 745-750, 2010.

Nudo R. J. Neural bases of recovery after brain injury. Journal of communication disorders, 44(5), 515-520, 2011.

Pascual-Leone A., Amedi A., Fregni F., Merabet L.B. The plastic human brain cortex. Annu Rev Neurosci;28:377–401, 2005.

Prabhakaran S., Zarahn E., Riley C., Speizer A., Chong J.Y., Lazar R.M., Marshall R.S., & Krakauer J.W. Inter-individual variability in the capacity for motor recovery after ischemic stroke. Neurorehabilitation and neural repair, 2007.

Quartarone A., Rizzo V., Bagnato S., Morgante F., Sant'Angelo A., Romano M., et al. Homeostatic-like plasticity of the primary motor hand area is impaired in focal hand dystonia. Brain; 128, 1943–1950, 2005.

Ramachandran V.S., Rogers-Ramachandran D., Cobb S. Touching the phantom limb. Nature;377:489-490, 1995.

Rehme A.K., Eickhoff S.B., Rottschy C., Fink G.R. & Grefkes C. Activation likelihood estimation meta-analysis of motor-related neural activity after stroke. Neuroimage, 59(3), 2771-2782, 2012.

Rizzolatti G., & Craighero L. The mirror-neuron system. Annu. Rev. Neurosci., 27, 169-192, 2004.

Sawaki L., Boroojerdi B., Kaelin-Lang A., Burstein A.H., Bütefisch C.M., Kopylev L., Davis B. & Cohen L.G. Cholinergic influences on use dependent plasticity. J Neurophysiol; 87:166–171, 2002.

Sawaki L., Werhahn K.J., Barco R., Kopylev L. & Cohen L.G. Effect of an alpha(1)-adrenergic blocker on plasticity elicited by motor training. Exp Brain Res;148:504–508, 2003 (a).

Sawaki L., Yaseen Z., Kopylev L., Cohen L.G. Age-dependent changes in the ability to encode a novel elementary motor memory. Ann Neurol; 53:521–524, 2003 (b).

Smania N., Paolucci S., Tinazzi M., Borghero A., Manganotti P., Fiaschi A., Moretto G., Bovi P. & Gambarin M. Active finger extension a simple movement predicting recovery of arm function in patients with acute stroke. Stroke, 38(3), 1088-1090, 2007.

Stefan K., Cohen L.G., Duque J., Mazzocchio R., Celnik P., Sawaki L., Ungerleide L. & Classen J. Formation of a motor memory by action observation. The Journal of Neuroscience, 25(41), 9339-9346, 2005.

Takeuchi N. & Izumi S.I. Rehabilitation with poststroke motor recovery: a review with a focus on neural plasticity. Stroke research and treatment, 2013.

Turrigiano G.G. Homeostatic plasticity in neuronal networks: the more things change, the more they stay the same. Trends Neurosci;22(5):221-7, 1999.

Uswatte G. & Taub E. Constraint-induced movement therapy: a method for harnessing neuroplasticity to treat motor disorders. Progress in brain research, 207, 379-401, 2012.

van Kordelaar J., van Wegen E. & Kwakkel G. Impact of Time on Quality of Motor Control of the Paretic Upper Limb After Stroke. Archives of physical medicine and rehabilitation, 95(2), 338-344, 2014.

Volpe B.T., Lynch D., Rykman-Berland A., Ferraro M., Galgano M., Hogan N., Krebs H.I. Intensive Sensorimotor Arm Training Mediated by Therapist or Robot Improves Hemiparesis in Patients With Chronic Stroke. Neurorehabilitation and Neural Repair, 22(3), 305-310, 2008.

Wolf S.L., Winstein C.J., Miller J.P., Taub E., Uswatte G., Morris D., Giuliani C., Light K.E. & Nichols-Larsen D. Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE randomized clinical trial. Jama, 296(17), 2095-2104, 2006.

Wolf S.L., Winstein C.J., Miller J.P., Thompson P.A., Taub E., Uswatte G., Morris D., Blanton S., Nichols-Larsen D. & Clark P.C. Retention of upper limb function in s



  • There are currently no refbacks.