Pharmacotherapy in Neurorehabilitation: What Can We Transfer from Adult to Children or “Neurological Enhancement”

Functional motor disability is most common following stroke. Treatment for improving motor functions laid so far solely in physiotherapy. In animal models, however, motor recovery has been shown improve depending on increase of norepinephrine concentration in the CNS in addition to exercises. We showed many studies with amphetamines, and other substances increasing concentration directly or indirectly of norepinephrine or dopamine.

As L-dopa is metabolized into norepinephrine, a prospective, randomized placebo-controlled double-blind clinical study was performed to investigate whether single doses of 100 mg L-dopa enhance the efficacy of physiotherapy for hemiplegia. In an AB-design motor function was quantitatively measured by Rivermead Motor Assessment (RMA) as well as in the activities of daily living (BI). Also, the effects were related to lesion side and lesion size as well as spasticity. Besides influences on neuropsychological functions such as visual neglect, verbal learning and attention were assessed.

The results showed a significant improvement on motor recovery both for the period of drug intervention (phase A) in the L-dopa group compared with the placebo group. The improvement was independent of the initial level of impairment and could be shown in the subgroup of mildly affected patients. The gain of motor recovery by adjuvant L-dopa was maintained at study endpoint 3 weeks after L-dopa was stopped (phase B) and appeared also in significantly improved ADL motor functioning such walking distance and speed. This gain appeared to be independent of lesion size or other concomitant neurological signs. Adjuvant L-dopa treatment led to functional improvements also in the treatment of neglect, yet without improving attention. It seems that it is the process of learning i.e., the new formation of synaptic connectivity which is supported by L-dopa. It also seems that this effect is stable over time once established.

In summary, since it could be shown that single doses of L-dopa given in addition to physical therapy enhance motor recovery in patients with hemiplegia, L-dopa can be recommended—in view of its minimal side effects—in conjunction with exercise therapy to improve functional outcome in stroke rehabilitation. At the end, we discuss possible pathophysiological answers.