BACKGROUND: Early/intensive mobilization may improve functional recovery after stroke but it is not clear which kind of "mobilization" is more effective. Proprioceptive neuromuscular facilitation (PNF) and cognitive therapeutic exercise (CTE) are widespread applied in post-stroke rehabilitation but their efficacy and safety have not been systematically investigated. AIM: To compare PNF and CTE methods in a two different time setting (early versus standard approach) in order to evaluate different role of time and techniques in functional recovery after acute ischemic stroke. DESIGN: We designed a prospectical multicenter blinded interventional study of early versus standard approach with two different methods by means of both PNF and CTE. SETTING: A discrete stroke-dedicated area for out-of-thrombolysis patients, connected with two different comprehensive stroke centres in two different catchment areas. POPULATION: Three hundred and forty consecutive stroke patient with first ever sub-cortical ischemic stroke in the mean cerebral artery (MCA) territory and contralateral hemiplegia admitted within 6 and 24 hours from symptoms onset. METHODS: All patients were randomly assigned by means of a computer generated randomization sequence in blocks of 4 to one to the 4 interventional groups: early versus delayed rehabilitation programs with Kabat's schemes or Perfetti's technique. Patients in both delayed group underwent to a standard protocol in the acute phase. PRIMARY OUTCOME: Disability at 3 to 12 months. DISABILITY MEASURES: Modified Rankin Score and Barthel Index. SAFETY OUTCOME: Immobility-related adverse events. SECONDARY OUTCOME MEASURES: Six-Minute Walking Test, Motricity Index, Mini-Mental State Examination, Beck Depression Inventory. RESULTS: Disability was not different between groups at 3 months but Barthel Index significantly changed between early versus delayed groups at 12 months (p = 0.01). Six-Minute Walking Test (p = 0.01) and Motricity Index in both upper (p = 0.01) and lower limbs (p = 0.001) increased in early versus delayed groups regardless rehabilitation schedule. CONCLUSIONS: A time-dependent effect of rehabilitation on post stroke motor recovery was observed, particularly in lower limb improvement. According to our results, rehabilitation technique seems not to affect long term motor recovery.

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