Ruolo farmacologico nel recupero motorio post-stroke: correlazione tra dato neurofisiologico (TMS) e clinico

Background. Stroke is one of the leading causes of death and the major cause of disability in Western Countries. Despite the introduction of new prevention strategies and acute stroke therapies, the outcome of stroke is still unsatisfactory. Functional rehabilitation plays a major role in reducing stroke disability. In recent years, animal and human studied added new information on the neuroplastic events taking place during recovery after stroke. These events involve ipsi-lateral and contra-lateral cortical areas, as well as sub-cortical and cerebellar structures and suggest large-scale changes in the central nervous system. Based on these experimental evidences, new rehabilitation strategies have been suggested to improve motor outcome after stroke. These strategies include constraintinduced movement therapy, drug modulation, non-invasive brain stimulation (NIBS), modulation of peripheral afferents, combined approaches (NIBS or drugs + conventional rehabilitation). Several drugs (dopaminergic, noradrenergic and serotoninergic drugs, amphetamines) have been tested in stroke rehabilitation, but the conclusions are still controversial. Aim of the study. We investigated the possible role of drug modulation in addition to conventional rehabilitation to enhance motor recovery after stroke. To this aim, we tested the effect of two selective serotoninergic reuptake inhibitors (SSRI, citalopram and paroxetine) and a dopaminergic drug (LEVODOPA) on outcome and neurophysiological measures in stroke patients. Materials and Methods. In experiments 1 and 2, 40 acute stroke patients were studied. All the patients had the stroke event 15 to 30 days before enrolment. The patients were randomly assigned to the SSRI (paroxetine 20 mg/die or citalopram 10 mg/die) or to the placebo. Motor outcome was examined using global assessment and segmental motor function scales. Motor cortex excitability was studied (in citalopram versus placebo-group) by single and paired transcranial magnetic stimulation (TMS) using the following measures: resting motor threshold (RMT), motor evoked potential (MEP) amplitude and latency, MEP recruitment curve, cortical silent period (CSP) duration, short-latency intra-cortical inhibition (SICI) and intra-cortical facilitation (ICF). Motor and neurophysiological measures were assessed at enrolment (T1) and at 5 weeks (T2). In experiment 3 we explored the possible role of LEVODOPA on modulation to enhance motor recovery after chronic stroke in 12 patients. Motor outcome was examined using global assessment and segmental motor function scales. Motor cortex excitability was studied (in citalopram versus placebo-group) by single and paired transcranial magnetic stimulation (TMS) using the following measures: resting motor threshold (RMT), motor evoked potential (MEP) amplitude and latency, cortical silent period (CSP) duration. Results. No significant difference was found in outcome measures in Paroxetina-group. In citalopram-group, a significant increase in NIHSS (p=0,03) was found. A significant increase in ICI (p<0.03) and in RMT (p<0,4) from the intact hemisphere (IH) was found in the SSRI group while no significant change was found in the stroke hemisphere (SH). We found in LEVODOPAgroup a increase in NHPT (p=0,01) and in 6MWT (p=0,01). Conclusions. Our findings suggest that drug administration may modulate cortical excitability after stroke. Outcome measures seem to be in part influenced by SSRI and dopaminergic drug in our patients. Reasons for this result may include the small number of patients and/or the stroke location. Further studies and new outcome measures, including new neurophysiological measures, are necessary to further investigate the effect of drugs on stroke motor recovery.