Authors

1. Tilley, Erica BSpPath (CPSP)
2. White, Sarahlouise BSc, (Hons), MClinSci, PhD
3. Peters, Micah BHSc MA(Q), PhD
4. Koblar, Simon A BMBS, FRACP, PhD
5. McLoughlin, James BAppSc (Physio), MSc (ClinNeurosci)

Abstract

Review question/objective: The objective of this review is to present the best available evidence related to allied health therapy in the symptomatic management of progressive supranuclear palsy (PSP). More specifically, the review question to be addressed is:

* What are effective physiotherapy, occupational therapy and speech therapy techniques used in the symptomatic management of PSP?

Background: Progressive supranuclear palsy, or sometimes known as Steele-Richardson-Olsewski syndrome, is a rapidly degenerative neurological disorder. The average age of onset is 60-65 years with a life expectancy of six to seven years following diagnosis.1 The main symptoms of PSP typically include vertical gaze palsy (difficulty looking up or down), postural imbalance and falls, dysphagia (difficulty eating or drinking) and/or dysarthria (speech disorder).2 Progressive supranuclear palsy belongs to the class of neurodegenerative conditions called tauopathies. Aggregation of the protein tau in neurons can lead to damage in both cortical and subcortical areas of the brain.3

Progressive supranuclear palsy is a severe disorder that is under recognized and underdiagnosed.4 It is an insidious condition with devastating impacts on individuals, their families, and the health resources of the broader community.5 This review will focus solely on PSP; however, in order to understand this seemingly obscure condition, it is important to first discuss the class of neurological conditions to which it belongs and the trends in prevalence of these conditions.

Progressive supranuclear palsy is a Parkinsonian condition, more specifically an atypical Parkinsonian condition. Parkinsonian conditions are a class of neurological disorders characterized by parkinsonism type symptoms such as slowness of movement, difficulty initiating movement, and rigidity with or without resting tremor.6 Parkinson's disease is the most common type. There is also a collection of conditions that may initially present similar symptoms to Parkinson's disease, but as the disease progresses they evolve in a critically different way to Parkinson's disease.6 These conditions have been named atypical Parkinsonian or Parkinson's plus syndromes. As mentioned, PSP is one type of atypical Parkinsonian conditions, others include multiple system strophy (MSA) and dementia with Lewy bodies.6 The key differences between Parkinson's disease and atypical Parkinsonian conditions have been summarized in Table 1 taken from Litvan.6

The similarities and differences of Parkinson's disease and atypical Parkinsonian conditions begin to illustrate the complexities of PSP. People with Parkinson's disease and PSP all present with parkinsonism symptoms. Unlike most presentations of typical Parkinson's disease, people with PSP experience rapid progression of their disorder, early instability or falls, early dysphagia and/or dysarthria without the alleviating benefits of levodopa6 or an alternative effective medication.7 They experience an economic burden of disease high above that reported for Parkinson's disease,5 and may remain undiagnosed for approximately half of the natural history of their disease.8

As mentioned previously, PSP is a seemingly obscure disorder. To appreciate the true scale of the disorder it is necessary to explore the difficulties in defining, diagnosing and therefore ascertaining the actual prevalence of PSP. These difficulties, against the backdrop of a recent generalized trend of increasing prevalence of all neurodegenerative disorders14, paint a different picture.

It is interesting to consider that the prevalence of PSP has been estimated to be 6.5 per 100,000,8 similar to the prevalence of motor neuron disease (MND),1 a far more well-known neurodegenerative disorder. Six of the seven states in Australia have their own MND Association, while there is only one PSP Association.9 The difference in the level of services and awareness of two conditions with a similar prevalence may be related to how easily they can be defined. Historically, MND was more readily accepted as a separate morbid entity due to a distinctive clinical and pathological presentation in comparison to PSP.1

Diagnosis of PSP continues to be a complex process, as demonstrated by a 41% misdiagnosis rate.8 Progressive supranuclear palsy is difficult to discern from Parkinson's disease due to an overlap in presenting symptoms.6,8 It is also commonly misdiagnosed as stroke.8 Autopsy continues to be the gold standard in the diagnosis of PSP.7 The National Institute of Neurological Disorders and Stroke (NINDS) and the Society for PSP (SPSP) have developed criteria to assist the clinical diagnosis of PSP10 which has been summarized in Table 2. Clinical diagnosis utilizing the NINDS-SPSP criteria is frequently used in studies researching PSP, presumably due to the difficulties obtaining autopsy results from participants. A recent study11 comparing the diagnostic accuracy of NINDS-SPSP against the gold standard of autopsy identified that NINDS-SPSP's probable criteria is appropriate for recruitment into clinical trials where an early and specific diagnosis is important.11 In the case of routine care where high sensitivity is crucial, a combination of NINDS-SPSP's possible and probable criteria is more suitable.11 The NINDS-SPSP criteria was first published in July 1996, therefore clinical studies completed prior to this time would not have had access to an appropriate recruitment method.

Mandatory exclusion criteria:

* Recent history of encephalitis

* Alien limb syndrome, cortical sensory deficits, focal frontal or temporoparietal atrophy

* Hallucinations/delusions unrelated to dopaminergic therapy

* Cortical dementia of Alzheimer's type

* Prominent early cerebellar symptoms

* Prominent, early unexplained autonomic dysfunction

* Severe asymmetric Parkinsonian signs

* Neuroradiologic evidence of relevant structural abnormality i.e. basal ganglia or brainstem infarcts

* Whipple's Disease

The NINDS-SPSP clinical diagnosis criteria have been utilized in the prevalence study by Nath et al.8, which estimated the crude prevalence of PSP to be 6.5 per 100,000. A recent publication has suggested that the prevalence of PSP has been radically underestimated in clinical studies.12 Kovacs et al.13 identified two cases of pathologically confirmed PSP in their community drawn autopsy population (n=233) with a further five cases of anatomically restricted forms of PSP. In their study, 3% of their population had confirmed PSP or anatomically restricted forms of PSP.

The radical difference in the number of people identified with PSP may be in part attributed to the diagnostic method used, with autopsy being the gold standard. The study by Kovacs et al.13 was published 12 years after the study by Nath et al.8 It is possible that the population studied by Kovacs et al.13 inherently had a higher prevalence of PSP than the population by Nath et al.8 due to an ageing population and an increase in possible environmental triggers, as will now be explored.

More broadly, there is an increase in prevalence of all types of neurodegenerative conditions. This is in part attributed to an ageing population with more people living long enough to acquire disorders that occur later in life.14 An increase in neurological deaths (deaths due to an underlying pathology such as Parkinson's disease and MND) has also been observed in younger age -groups and females from 1979 to 2010.15 The possibility of modern environmental factors (increased population, pollution and exposure to electro-magnetic fields) triggering existing underlying genetic predispositions has also been raised.15

This increase in prevalence of neurodegenerative disorders is a major public health problem14,15 and raises serious implications on families and health and social care services15 as in the case of Parkinson's disease. In the United States of America (USA), the economic burden of Parkinson's disease was 14.4 billion (USD) for the year of 2010. The projected prevalence of Parkinson's disease, and therefore associated cost, is expected to double by 2040.16 No such study has been completed for PSP; however, it is known that per person, the economic burden of disease for PSP is high above reports for Parkinson's disease.5 If the prevalence of PSP doubles in line with the expected trend of Parkinson's disease, the future economic burden of the disorder will be significant. There is an acute need for further evaluation of the economic impact of PSP.

Symptoms and current approaches to the management of PSP

People with PSP experience a range of symptoms2 that reduce quality of life across mobility, self-care, usual activities, pain/discomfort and anxiety/depression domains.17 Mobility problems, visual symptoms, speech and swallowing problems are most commonly experienced.2 Symptoms of PSP continue to be defined and studies have since explored cognitive disturbances further18,19. A summary of the main symptoms experienced by people with PSP has been developed from a preliminary search of the literature and from publications from PSP associations including CurePSP (USA),20 the PSP Association (UK)21 and PSP Australia9 (see Table 3).

Progressive supranuclear palsy is challenging to treat due to the widespread involvement of both dopaminergic and nondopaminergic systems.10 Currently, there are no curative treatments available.7 A multidisciplinary team is considered to be integral to the symptomatic management of PSP.24 In practice, there are a number of therapies used.4, 20, 22, 25, 26

This systematic review will focus on the interventions that can be delivered by the following three disciplines: physiotherapy/physical therapy, occupational therapy, and speech therapy/speech pathology/speech-language-pathology. Mobility, speech and swallowing problems are some of the most commonly experienced symptoms by people with PSP and are experienced across all stages of the disease.2 Aspiration pneumonia and other consequences of reduced mobility such as pulmonary embolism are the leading cause of death.27

A number of management therapies are used in practice however their effectiveness in improving quality of life or survival time has not been evaluated systematically.22 Current therapies have been summarized in Table 4 from a preliminary search of the literature and from publications from PSP Associations including CurePSP (USA),20 the PSP Association (UK)21 and PSP Australia.

For the purposes of this systematic review, the main outcomes of interest include evaluations of physiotherapy, occupational therapy, or speech therapy interventions in the management of people with PSP. These will include measurements of:

* Quality of life (PDQ39)28

* Survival time

* General functioning (Unified Parkinson's Disease Rating Scale)29

And any other outcome measure of the symptoms listed in Table 3 or consequences of the symptoms listed in Table 3 (such as episodes of aspiration pneumonia or number of fractures from falls).

A preliminary search of the Joanna Briggs Database of Systematic Reviews and Implementation Reports, the Cochrane Library, CINAHL, PubMed, PROSPERO, Health Informit, PsycINFO, PEDRO, OTSeeker, SpeechBite has revealed that there is not currently a systematic review (either published or underway) on this topic.