Progressive Supranuclear Palsy-a Mirror Image of Parkinson’s Disease, A Literature Review of Rehabilitation Strategies

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease which mimic similar to Parkinsonism. PSP advances much quicker than in PD yet no effective medication or therapy to manage PSP available. This literature review aimed to discover the recent advances in the physical therapy treatment options for PSP. Databases such as PubMed, Elsevier and SAGE journal searched for both published and unpublished studies. Last 10-year studies were included in this review. Limited clinical trial conducted in this population due to which a structured protocol or rehabilitation strategies is missing for this condition. Balance exercise and gait training showed potential benefit and music-cued walking demonstrated participant’s satisfaction.


INTRODUCTION
Progressive supranuclear palsy (PSP) or Steele Richardson-Olszewski syndrome, is a rare neurodegenerative disease first described in 1963 by John Steele, J clivord Richardson and Jerzy Olszewski. [1,2] Which is earlier classified among atypical Parkinsonism, that is often Review Article misdiagnosed as Parkinson's disease due to its similar presentation. Supranuclear vertical gaze palsy, frequent falls, rapid deterioration in balance, greater axial rigidity than appendicular rigidity, speech disturbance, fatigue and cognitive impairment are the characteristic features of this fast-progressing condition. Restriction of vertical gaze with preserved oculocephalic reflexes is the most specific and characteristic feature of PSP. Based on the clinical presentation PSP clinical stages are divided into three, early stage, middle and late stage [3][4][5][6].
PSP Affecting around a million people worldwide of 5-6 cases per 100,000 [7]. Patients with PSP are typically 3 years from their first symptom before they get diagnosed. Based on one study in a southern Italian population, 7.1 year is the mean survival of PSP and a median survival of between 5.3 and 10.2 years since the onset of symptom according to 2017 metaanalysis [8,9].
Progressive supranuclear palsy is a tau-opathy. Tau, present in the central nervous system, is a Microtubule-associated protein (MAPS) as well as a cytosolic protein, primarily present in axons and participate in anterograde axonal transport. [11,12] Under normal physiological circumstances It facilitates microtubule assembly and stabilization of microtubule. Tau protein may get altered in certain pathological conditions, through phosphorylation, which results in the production of aberrant aggregates or a diverse expression of some of its isoforms that are toxic to neurons. This process is known as tauopathies which provoke pathological effects in PSP. [12][13][14].
The build-up of tau protein and neuropil threads is seen in PSP, mainly in the basal ganglia structures like pallidum, substantia nigra, subthalamic nucleus, red nucleus, etc., furthermore multiple subcortical and brain stem nuclei have been reported with marked neuronal degeneration and gliosis. [15,16] [26,27]. PSP patients having symmetrical limb signs, no tremor, and axial rigidity which is exclusively seen in the trunk and neck, and less rigidity noted in the periphery. [28] In addition laboratory tests and imaging exams can be used rule out other pathologies to narrow down the diagnosis [29].

The Diagnosis of PSP
Since the preliminary clinical features appear like PD, [30,31] with the wrong diagnosis several patients are referred for rehabilitation services. PSP advances much faster than in PD yet no effective medication or cure to manage PSP available. Physical therapists must be aware of the peculiarity this condition to guarantee that the patients are diagnosed and rehabilitated appropriately however there is no strong existing literature evidence backing its effectiveness in spite of the demand for rehabilitation in this population. To address this existing fact, this literature review aimed to discover the recent advances in the physical therapy treatment options for PSP and to make proposals for the plan of exercise programmes.

METHODOLOGY
In order to gain a better insight into the effectiveness of exercise for the improvement of the patient with PSP, various previously published articles were studied thoroughly. The following databases were searched for both published and unpublished studies-PubMed, Elsevier and SAGE journal. Last 10-year studies were included.

Exclusion Criteria
Parkinson's Disease, review, Manuscript, Books and Documents

RESULTS
From a yield of numerous studies, finally only 7 studies were selected depending upon the inclusion and exclusion criteria.

DISCUSSION
Progressive supranuclear palsy is a neurological condition which is similar and misdiagnosed mostly as Parkinson's diseases. Even though many are affected because to this condition fewer research work is conducted in this field due to the misdiagnosis or obvious unawareness from the researchers. From the last 10-year search results we could barely find few articles which has done clinical trial in this population. Mostly we could find case report and case series during the search strategies.
From this literature review we could identify 7 articles, out of which 2 are systematic review and 6 were experimental study.

1)
A study done by Anna D Hohler in patients with AP to find the effectiveness of an inpatient movement disorders program in 2012. 91 patients with AP were participated in the study in which 4 were PSP patients. The program consisted of speech, occupational and physical therapy for 3 hours per day, per week5 to 7 days. Pharmacologic modifications were also done based on daily observation and data. 6 studies were included in the review. All six studies utilized different physiotherapy interventions such as a dynamic antigravity postural system (SPAD) and a vibration sound system (VISS) rehabilitation program, audio feedback during posture and balance training, balance and eye movement training, walking with robotic assistance and treadmill training with body weight support. Total of 4 case series, case study with single participant. One study examined a non-invasive brain stimulation therapy using rTMS. Five studies used interventions currently considered within the scope of practice for physiotherapy. The program consiste SPAD and VISS treatments was conducted for 2 months, three sessions per week with each session of 20 minutes. Patients encouraged to walk by suspending the patient weights using mechanical vertical traction system and made to walk on a treadmill.
In another case series conducted in 2010, the intervention was done for three times in a week with 45 minutes in each session. A total duration of 6weeks to improve balance by balance and posture exercises with the help of audiobiofeedback. A sensor with audio biofeedback system, worn near the canter of mass intended to measure acceleration of trunk along the sagittal axis and frontal axes.
Sale et al done a case series in five PSP patients underwent 45 minutes rehabilitation using robotassisted walking devise, weekly five times for 1 month, in comparison with baseline measurements. The participants trained floor walking (5-30minutes) followed by repetitive simulated stair climbing (5-10 min) up and down.
Effectiveness of repetitive transcranial magnetic stimulation in improving gait/midline symptoms was the objective of the study done by Santens et al in 2009. The rTMS procedure comprised of 10hz stimulation for 5 s, with 55 s rest was given after that. A repetition of 20 times per session, 5 consecutive days undertaken by 6 participants. Baseline measurements was the comparator.

3) In 2017 Ilaria Clerici done a study in 24
PSP patients to assess the effect robotic device lokomat training in comparison with treadmill training through visual cues and auditory feedbacks. They enrolled a total of 24 PSP patients, out of which twelve subjects underwent a 1month multidisciplinary intensive rehabilitation treatment (MIRT) exploiting the use of the treadmill-plus and the remaining 12 participants underwent the same treatment, however replacing the treadmill-plus with lokomat.
PSP rating scale (PSPrs) were used as primary outcome in addition berg balance scale (BBS), six minutes walking test (6mwt) and the number of falls were also taken as a secondary outcome measure. Total of 24 patients assigned into two group of 12 each. Both groups underwent 4 weeks training. Group 1 was MIRT group they underwent a treadmill training combined with with visual cues and auditory feedbacks (treadmillplus). On the other hand group 2, the MIRTlokomat group, underwent MIRT replacing the treadmill-plus with lokomat1. MIRT includes aerobic, multidisciplinary, intensive, motorcognitive and goal-based rehabilitation treatment. It 4 sessions/ day for 5days/week. MIRT group underwent 20-minutes treadmill-plus training /day 5 times a week. Using gait trainer 3 biodex, speed of treadmill increased maximum of 2.5 km/h from an initial 1.0±1.5 km/h. Visual cues and auditory feedbacks were used during the training. Lokomat1, a gait robot, is a driven-gait orthosis that permits gait on a treadmill by simulating physiological stride pattern of the human. The study concluded with the following findings. Improvement of BBS score along with reduction in the fall incidences. Indicating both MIRT and the MIRT-lokomat improves balance dysfunction. In addition, 6mwt and PSPrs-gait score improved, suggesting that in PSP patient's treadmill-plus and lokomat, used in the context of MIRT, provided benefits. MIRT-lokomat group achieved remarkable functional improvements. Since it provides proprioceptive and exteroceptive feedbacks which allow patients walk repetitively. Furthermore, the MIRT group shown better PSPrs-limb score with trunk muscles active involvement. Author concluded that lokomat does not add additional benefits within a protocol like MIRT.

4)
Wittwer, j. E.et all done a study to improve gait speed and stability in PSP patients using supervised, home-based, music-cued training to improve gait speed and stability in PSP patients. Experienced physiotherapists over 4 weeks conducted one-hour training two times in a week, with and without auditory cues which included standing or walking activities. Using an 8m long gaitrite® mat spatiotemporal gait measures were documented. At self-selected comfortable pace participants walked without cues. The study results exhibited that out of five PSP patients two patients walked with normal speed and low gait unevenness. The author concluded that with the support of caregiver, home program with music cued gait training can improve gait issues.

5)
In 2019, Susan C. et al Published a systematic review in PSP to evaluate the effect of exercise and physical activity interventions. All the study until 2018 was added. 11 studies were included with a total number of 99 patients. Treadmill training with harness support, robot-assisted gait rehabilitation and auditory-cued motor training found to have primary evidence as a useful rehabilitation in the early stages.
Total of 3 RCT were included in the systematic review. One was using locomote for gait training for 4weeks. Other two was exercises training which has sit-to-stand and stand-to-sit practice on a chair, tandem stance practice with eyes open and closed, marching in place while turning 360° for 1hour every day for 3 days in a week in a 4 weeks program. Most of the other studies were cohort and case study which included training such as posture improvement strategies using weighted vest, robot-assisted walking for 4 weeks, weight relieving harness for walking (SPAD) plus vibration sensory stimulation (VISS) and dynamic exercises such as sitting, standing, transfers, sway, reaching or stepping one direction and multi direction stepping for 6 weeks. Different complex equipment's was used for the intervention however, strength training and physical activity having positive benefits in older adults and they are well established for general health also.

6)
Yamato at el done a clinical trial in 2019 in patients with Parkinson's disease (PD) or atypical parkinsonism, to clarify the mid-term results of extensive spinal fusion surgery Out of 22 Parkinson patients 2 were PSP patients. Patients who underwent extensive fusion surgery more than 5 years prior were included. Criteria assessed was perioperative and mechanical complications, surgical and radiographic parameters and indoor ADL over time. Short term outcome was good; yet, the patients' conditions worsened due to complications within 3 years and due to the disease progression.

7)
To discover whether in PSP patient's language capacities can be improved by transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) Valero-cabré, a at el did a study in 2019 .12 patients were participated in the study. Compared to sham tDCS the capacity to boost the left DLPFC via left-anodal (excitatory) and right-cathodal (inhibitory) tDCS was higher. Before and after the tDCS, Letter fluency task and category judgment task were tested immediately. Contrasting poststimulation vs prestimulation performance across tDCS conditions revealed language improvement in the category judgment task.

CONCLUSION
PSP is a progressive neurological disorder, which misdiagnosed mostly as Parkinson disease. We could find there is limited clinical trial happening in this population due to which a structured protocol or rehabilitation strategies is missing in this population. From the article we analysed the systematic review available on this condition are based on the Cohort and case studies only. Very minimal RCT are conducted due to which drawing a conclusion is meaningless. However, Balance exercise and gait training showed potential benefit and musiccued walking demonstrated participant's satisfaction. walking speed and quality were associated with music-cued movement rehabilitation, weight-supported treadmill training and robotic gait training.

FUTURE IMPLICATION
 Clinical trials with large sample size in the population must be conducted to throw light upon the effects of physical therapy on PSP patients.  Should also try the rehabilitation benefits in different stages of PSP

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.
concepts and diagnostic challenges. The