AUTHOR=Putortì Alessia , Corrado Michele , Avenali Micol , Martinelli Daniele , Allena Marta , Cristina Silvano , Grillo Valentina , Martinis Luca , Tamburin Stefano , Serrao Mariano , Pisani Antonio , Tassorelli Cristina , De Icco Roberto TITLE=The Effects of Intensive Neurorehabilitation on Sequence Effect in Parkinson's Disease Patients With and Without Freezing of Gait JOURNAL=Frontiers in Neurology VOLUME=Volume 12 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.723468 DOI=10.3389/fneur.2021.723468 ISSN=1664-2295 ABSTRACT=Background: The sequence effect (SE), defined as a reduction in amplitude of repetitive movements, is a common clinical feature of Parkinson’s disease (PD), and is supposed to be a major contributor to freezing of gait (FOG). During walking, SE manifests as a step-by-step reduction in step length when approaching a turning point or gait destination, resulting in the so-called destination sequence effect (dSE). Previous studies explored the therapeutic effects of several strategies on SE, but none of them evaluated the role of an intensive rehabilitative program. Objectives: Here we aim to study the effects of a 4-week rehabilitative program on dSE in patients with PD with and without FOG. Methods: Forty-three patients (30 males, 70.6±7.5 years old) with idiopathic PD were enrolled. The subjects were divided into two groups: patients with (PD+FOG, n=23) and without FOG (PD-FOG, n=20). All patients underwent a standardized 4-week intensive rehabilitation in-hospital program. At hospital admission (T0) and discharge (T1), all subjects were evaluated with inertial gait analysis for dSE recording. Results: At T0, the dSE was more negative in PD+FOG group (-0.80±0.6) when compared to PD-FOG group (-0.39±0.3) (p=0.007), even when controlling for several clinical and demographic features. At T1, the dSE was reduced in the overall study population (p=0.001), with a more pronounced improvement in PD+FOG group (T0: -0.80±0.6; T1: -0.23±0.4) when compared to PD-FOG group (T0: -0.39±0.3; T1: -0.22±0.5) (p=0.012). At T1, we described in the overall study population an improvement in speed, cadence, stride duration, and stride length (p=0.001 for all variables). Conclusions: dSE is a core feature of PD gait dysfunction, specifically in patients with FOG. A 4-week intensive rehabilitative program improved dSE in PD patients, exerting a more notable beneficial effect in the PD+FOG group.