Neurorehabilitation of Sequence Effect in Parkinson's Disease
Condition: Parkinson Disease; Freezing of Gait
MeSH terms: Parkinson Disease
Study type: Observational

Summary: 
      The sequence effect (SE), defined as a reduction in amplitude of repetitive movements, is a
      common clinical feature of Parkinson's disease (PD), being a major contributor to freezing of
      gait (FOG). During walking, SE manifests as a step-by-step reduction in step length when
      approaching a turn or gait destination (dSE). The investigators studied the effect of a
      4-week rehabilitation program on the destination sequence effect in patients affected by
      Parkinson's disease with and without Freezing of Gait. All subjects were evaluated with
      inertial gait analysis for dSE recording.
    

Detailed description: 
      Gait impairment and freezing of gait (FOG) represent common and disabling symptoms of
      Parkinson's disease (PD). The antiparkinsonian therapy positively modulates a subset of gait
      parameters, such as speed of gait and stride length, while its impact on FOG is limited.
      Growing evidence supports the efficacy of neurorehabilitation in the treatment of PD across
      all phases of the disease. In the last years, the advent of reliable wearable devices has
      prompted the widespread study of several parameters of the parkinsonian gait in both clinical
      and research settings.

      The sequence effect (SE), defined as a reduction in amplitude of repetitive movements, is a
      common clinical feature of several tasks of patients affected by PD, being identifiable in
      early as well as advanced stages of the disease. During walking, SE manifests as a
      step-by-step reduction in step length when approaching a turn or gait destination
      (destination sequence effect - dSE). SE is specifically pronounced in PD patients affected by
      FOG, and it arises immediately before a FOG episode induced by a turning or a dual-task.

      SE may be acutely modulated by several rehabilitative strategies such as split-belt treadmill
      and reinforcement of visual cues, but not by repetitive transcranial magnetic stimulation
      (rTMS), antiparkinsonian drugs administration, and attention strategies did not influence the
      SE, the evidence on the role of neurorehabilitation on gait SE improvement and retention is
      extremely scarce.

      The investigators plan to enroll 43 subjects according to sample size calculation. Patients
      will be divided into two groups: patients with freezing of gait (FOG) and without FOG. The
      subjects will be divided into two groups: 1) patients with freezing of gait (PD+FOG), or 2)
      patients without freezing of gait (PD-FOG). FOG phenotype is defined as: a score between 1
      and 4 at either item "2.13 Freezing" or item "3.11 Freezing of gait" of the Unified Parkinson
      Disease Rating Scale (UPDRS).

      All patients will be treated with a standardized 4-week rehabilitation in-hospital program.
      At hospital admission (T0), patients who fulfill inclusion/exclusion criteria will be tested
      with instrumental gait analysis and administration of a set of the following clinical scales:
      rating of PD related motor disability with the Unified Parkinson's Disease Rating Scale -
      part III (UPDRS-III); rating of functional independence as measured through the Functional
      Independence Measure (FIM); and rating of dependence in activity of daily living according to
      Barthel Index.

      After that, patients will be treated with 90-minute daily rehabilitative sessions, 6 days a
      week (Monday through Saturday) for four weeks (passive, active-assisted, and active
      exercises, isotonic and isometric exercises for the major muscles of the limbs and trunk,
      cardiovascular warm-up exercises, muscle stretching exercises for functional purposes,
      balance training exercises, specific motor exercise for hypokinesia, and 45 minutes of
      overground gait training delivered without devices or cueing). The rehabilitation program
      will be the same in PD+FOG and PD-FOG groups. At the end of the rehabilitation program (T1),
      the patients will complete the study procedure with a second instrumental gait analysis
      evaluation and the administration of the same set of clinical scales. No modifications of the
      drug regimen were allowed during the study.

      The gait analysis will be performed with wearable, wireless, inertial system, secured to the
      back of the patients between L5 and S1 vertebrae. All subjects will be recorded in the
      morning (between 9:00 a.m. and 11:00 a.m.) and in the ON condition. The investigators plan to
      record a walk, at a comfortable pace, of 20 meters. The subjects will stop independently at
      the end of the 20-meter pathway, clearly marked by a straight line on the ground. Gait
      assessments with episodes of freezing of gait or pauses will be discrded. For each subject,
      three optimal performed gait assessments will be recorded. Regarding gait parameters the
      investigators will record: speed (m/s), cadence (steps/minute), stride length (meter), step
      length (meter), stride duration (second), single support, double support, swing duration,
      stance duration (percentage stride distribution). The destination Sequence Effect (dSE) will
      be computed as a regression slope (β) of step length according to a previously described and
      validated methodology where step length is plotted against step number. Briefly, the length
      of the last six steps ahead of the final stride are plotted against the step number, and the
      linear regression slope (β) will represent a measure of dSE. In addition, the intercept (I)
      of the regression curve will be used as an indirect measure of gait hypokinesia. For each
      group, the relationship between gait hypokinesia and sequence effect is expressed by the
      function of the linear regression as follow: y = β (x) + I.
    

Intervention name(s): Neurorehabilitation
Intervention type(s): Procedure
Intervention description(s): All patients will be treated with an in-hospital rehabilitation program focused on the rehabilitation of gait disorder in PD with 90-minute daily sessions, 6 days a week (Monday through Saturday) for four weeks. The rehabilitation treatment includes passive, active-assisted, and active exercises, isotonic and isometric exercises for the major muscles of the limbs and trunk, cardiovascular warm-up exercises, muscle stretching exercises for functional purposes, balance training exercises, specific motor exercise for hypokinesia, and 45 minutes of overground gait training delivered without devices or cueing The rehabilitation program is the same in PD patients with and without FOG.
Other intervention name(s): Rehabilitation; Physical therapy
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients affected by Idiopathic Parkinson's disease with and without freezing of gait to be
        consecutively enroll among those attending the Neurorehabilitation Department of the IRCCS
        Mondino Foundation (Pavia, Italy)
      
Keywords: Movement disorders; Gait analysis; Hypokinesia; Basal ganglia; Functional indipendence