Rehabilitation in progressive supranuclear palsy: Effectiveness of two multidisciplinary treatments

Background to date, there are no medical or surgical treatments for progressive supranuclear palsy (PSP). It is possible to speculate that patients with PSP could benefit from rehabilitative treatments designed for Parkinson’s disease, including the use of robot-assisted walking training. Objective to evaluate whether the use of the robotic device Lokomat® is superior in PSP patients to the use of treadmill with visual cues and auditory feedbacks (treadmill-plus) in the context of an aerobic, multidisciplinary, intensive, motor-cognitive and goal-based rehabilitation treatment (MIRT) conceived for Parkinsonian patients. Methods we enrolled twenty-four PSP patients. Twelve subjects underwent a 4-week MIRT exploiting the use of the treadmill-plus (MIRT group). Twelve subjects underwent the same treatment, but replacing the treadmill-plus with Lokomat® (MIRT-Lokomat group). Subjects were evaluated with clinical and functional scales at admission and discharge. The primary outcomes were the total PSP Rating Scale (PSPRS) score and its “limb” and “gait” sub-scores. Secondary outcomes were Berg Balance Scale (BBS), Six Minutes Walking test (6MWT) and the number of falls. Results total PSPRS, PSPRS-gait sub-score, BBS, 6MWT and number of falls improved significantly in both groups (p ≤ 0.003 all, except 6MWT, p = 0.032 and p = 0.018 in MIRT-Lokomat and MIRT group respectively). The PSPRS-limb sub-score improved significantly only in the MIRT group (p = 0.002). A significant difference between groups was observed only for total PSPRS, indicating a slightly better improvement for patients in the MIRT group (p = 0.047). No differences between groups were revealed for the other outcomes, indicating that the effect of rehabilitation was similar in both groups. Conclusions Lokomat® training, in comparison with treadmill-plus training, does not provide further benefits in PSP patients undergoing MIRT. Our findings suggest the usefulness of an aerobic, multidisciplinary, intensive, motor-cognitive and goal-based approach for the rehabilitation of patients suffering from such a complex disease as PSP. Trial Registration This trial was registered on ClinicalTrials.gov, NCT02109393.


Introduction and rationale of the study
Progressive Supranuclear Palsy (PSP) (also known as Steele-Richardson-Olszewski Syndrome) is a neurodegenerative disorder first described in 1964. PSP shares different neuropathological and neurophysiological aspects in common with Parkinson's Disease (PD) and some data provide insight into a common deficit in both pathologies. A biochemical alteration in the tau protein, resulting in neurodegeneration and gliosis in the basal ganglia, brainstem, prefrontal cortex and cerebellum, is the neuropathological hallmark of PSP. The principal clinical features of PSP are: • Early postural instability with recurrent falls (principally backwards); • Visual dysfunctions (vertical supranuclear gaze palsy); • Neuropsychological deficits; After about 3.9 years from onset of the disturbances, the clinical picture becomes particularly distinctive. To date, there are no effective medical or surgical treatments for this disease. Patients rapidly become disabled and death generally occurs after about 6-7 years from the onset of the disorder.
Literature data support the efficacy of goal-based, aerobic, intensive and multidisciplinary rehabilitation treatments for PD patients. Nevertheless, data about the effectiveness of these physical approaches in PSP patients are not consistent and basic questions remain to clarify. As a matter of fact, the severe gait and  balance disturbances, together with the high risk of falls, limit the design of specific rehabilitation protocols for PSP patients.

I T A L I A H O S P I T A L S. p. A.
Gait is heavily impaired in PSP and causes imbalance: while walking the base of support is augmented, there is an important trunk retropulsion, posturo-kinetic instability and loss of the physiological postural reactive reflexes.
Given these premises, we hypothisize that the use of a robotic device such as Lokomat® could positively intervene on the typical gait and balance disturbances of PSP. Lokomat® is a driven-gait orthosis (gait robot) that allows gait by simulating physiological stride patterns and inducing a muscle coordination reflecting human walking. This robotic device is connected to a computer: the operator can set the gait parameters driven by the robotic orthosis (speed, stride length, range of motion of the knee and hips) on the basis of the clinical feature of each patient. Patients, in order to "actively" interact with the passive robot-driven movements, could use visual feedbacks provided by the computer. Therefore, it is arguable that Lokomat® could be a valid support for the rehabilitation of PSP patients. Anyhow it remains to be clarified the effectiveness of rehabilitative approaches designed for PD patients on subjects suffering from PSP.
The rehabilitative treatment known as MIRT (Multidisciplinary Intensive Rehabilitation Treatment) has been extensively described and it its effectiveness on motor and functional parameters has been demonstrated in PD patients. MIRT aims at functional recovery and motor re-learning. It consists of a 4-week physical therapy in a hospital setting and entails four daily sessions for five days per week organized as follows:

• From Monday to Friday à First session (1 h/day): it consists of a one-to-one session with physical therapist (front-to-front); Second session (1 h/day): it includes aerobic and repetitive activities to improve gait and balance using different devices (treadmill-plus with visual cues and auditory feedbacks, cycloergometer, crossover and posturographic platform with visual feedbacks); Third sessions (1 h/day): occupational therapy; Fourth session
(1 h/day): speech therapy.

Aims of the study
The aims of our study are: • To evaluate whether an aerobic, intensive, goal-based and multidisciplinary rehabilitation treatment such as MIRT, previously conceived for PD, is effective for PSP patients; • To evaluate, within MIRT, whether a robotic device, such as Lokomat®, is able to provide further benefits;

Materiali e Metodi
From January 2014 to December 2015, patients with a diagnosis of PSP, which will be hospitalized at the Department of Parkinson's Disease, Movement Disorders and Brain Injury Rehabilitation of the "Moriggia-Pelascini" Hospital (Gravedona ed Uniti, Italy), will be evaluated to be enrolled in the study.

Inclusion criteria:
• Diagnosis of PSP in accordance to the NINDS-SPSP International Criteria (Litvan et al., 1996); • Ability to walk unassisted for at least 6 meters; • Age 55-85; • Stable dopaminergic drugs dosage in the month preceding the admission to the study; Exclusion criteria: • Any others significant neurological or orthopedic disorders; • Osteoarthritis, osteoporosis, cutaneous lesions and/or other pressure wounds; • Body weight exceeding 135 kg (the weight limit for the use of Lokomat®); • Respiratory and cardiovascular diseases; Written informed consent will be requested to participants before the beginning of the study.
Patients will be randomly assigned to two groups (each group was composed of 12 patients) using a computer-generated list:

MIRT Group
This group will undergo a 4-weeks MIRT exploiting the use of a treadmill plus (treadmill associated with visual cues and auditory feedbacks); Treadmill-plus training à 20-minutes training per day, 5 times a week for 4 weeks.

MIRT+Lokomat Group
This group will undergo a 4-weeks MIRT involving the use of Lokomat® for 5 days per week in spite of treadmill-plus; Lokomat training à 20-minutes training per day, 5 times a week for 4 weeks.