Treatment-Induced Cortical Reorganization After Stroke in Humans

abstract & commentary

Source: Liepert J, et al. Treatment-induced cortical reorganization after stroke in humans. Stroke 2000;31:1210-1216.

Neurologists have made great efforts to prevent stroke and to reduce the degree of brain damage associated with acute stroke. They also have largely neglected rehabilitation efforts, although several important advances in that specialty have made important contributions. In any event, neuroscientific guidances have had little to add to present day peripheral physical therapy. Recent neuroscientific findings in both subhuman primates and humans, however, have identified considerable evidence of cerebral plasticity following injury. Much of this work indicates a capacity to restore at least a part of acute functioning losses due to either cerebral or even to peripheral arm-hand injuries. (For a brief review of both primate and human studies, see Liepert J, et al. Neurosci Lett 1998;250:5-8.)

One new example of neuroscience-engendered post-stroke rehabilitation consists of constraint-induced (CI) therapy for hemiparetics. The procedure involves constraining the patient’s remaining functional arm so as to force her or him to use the paretic member several hours daily, addressing and improving functional ability to perform activities of daily living (ADL). Outcomes have been favorably reported.

In this report, Leipert and colleagues describe a special protocol to evaluate two functional changes using vigorous CI therapy. The program was as follows: one aspect measured the physical recovery of manual activity following a stringent CI therapy period of 12 days. The other part mapped the size of the functional hand area in the damaged cerebrum using transcranial magnetic stimulation (TMS) applied to the scalp over the identified hand area. (The point of the latter technique was to map the size of the frontal motor hand area of the damaged cerebrum by evoking muscular responses from the impaired ipsilateral hand before and after a fixed, vigorous CI treatment protocol.) Using a motor activity log (MAL), physical recovery was quantified by testing improvements in 20 important ADL functions before and after the 12-day CI therapy.

Complete studies included 10 appropriate patients possessing approximately 20° of wrist and 10° of finger movements in the hemiparetic arm. Time after the acute stroke averaged 4.9 ± 5-7 years. Following baseline, pre-treatment clinical evaluations, and TMS motor studies, each patient underwent 12 days of CI therapy consisting of 12 ADL tasks plus 10 incorporated days of added, vigorous six-hour therapy related to a variety of rigorous tasks called "shaping." Patients wore immobilizing splint-slings on their nonparalyzed arm 90% of all 12 wakeful days. Results after treatment were evaluated as follows (parentheses indicate number of subjects): day 1 (1), week 4 (9), and 4 and 6 months (7). MAL improvement affected all patients proportionately to baseline levels that preceded the onset of the protocol. All patients physically improved. Four who had almost no hand use at the start gained only slight improvement but the remainder achieved half to three-fourths improvement over their baseline functions.

TMS brain mapping prior to the onset of testing indicated that the cerebral forearm-hand area contralateral to the paralysis was 60% less than its healthy, transverse counterpart. On the first post-testing day, the abnormal cerebral motor area reversed to +137% and six months later was approximately even to the other side. TMS motor-response threshold over the injured hemisphere was consistently elevated by about 50% above the normal hemisphere throughout.


The pragmatic result of this important report is: CI therapy, vigorously applied over a two-week period, can greatly improve movement in paralytic hands and forearms of poststroke hemiparetic patients when applied several years after onset. Using Leipert et al’s protocol, the beneficial response remained for at least six months and possibly much longer. The experimentally induced enlargement of the damaged cerebral motor hand area after the 12 successful CI treatment days must have reflected new afferent proprioceptive stimuli emanating from the previously immobile, now-moving hand. Such a rapid conclusion cancels the possibility that the enlargement could reflect either axonal regrowth or synaptic degeneration. Leipert et al propose that either a loss of activity from local cortical inhibitory neurons may simply "unmask" pre-existing connections or, conversely, synaptic strength increases in pre-existing connections. Several years ago, efforts somewhat like these were tried immediately after acute strokes without apparent effects and became largely abandoned. We cannot yet be sure that this delayed protocol will materially improve recovery of function when applied immediately following acute stroke. If the results can be promptly reproduced, however, neurologists should urge physical therapists to apply similar protocols as general health returns. —fp