Disorders

What is progressive supranuclear palsy?

Progressive supranuclear palsy (PSP) is a rare brain disorder that affects movement, balance, and eye movements. Many of the symptoms are similar to Parkinson’s disease, such as unsteady gait, stiff movements, and mild dementia.

• Progressive – means the symptoms get worse over time
• Supranuclear – refers to the part of the brain that is affected
• Palsy – means a weakness or paralysis in a part of the body

PSP symptoms can begin anywhere between age 40 to the late 80s, however the most common onset is in a person’s mid-60s (1). It is slightly more common in men than women. In the early stages, PSP can be misdiagnosed as Parkinson’s or Alzheimer’s disease due to the overlap in symptoms. 

There is no cure or disease-modifying treatment for progressive supranuclear palsy. Instead, treatment is focused on managing symptoms and giving the patient the best possible quality of life. 

Causes of progressive supranuclear palsy

Researchers do not know the exact cause of progressive supranuclear palsy. There has been some speculation about environmental causes (such as exposure to pesticides), but results have been inconclusive (2). In very rare cases, PSP can be genetic – either familial or associated with mutations in the MAPT gene (2).

While we don’t know what causes a person to get PSP, we do know what causes PSP symptoms. PSP causes damage to multiple brain cells, loss of the myelin sheath in some nerves, and destruction of the entire nerve in other areas. A person’s symptoms and disease progression will depend on which cells and brain regions are damaged.

PSP belongs to tauopathies, a family of diseases characterised by neuron loss, gliosis, and accumulation of tau protein in the brain (2). Alzheimer’s disease is the most common and well-known tauopathy.

Symptoms

Symptoms of progressive supranuclear palsy affect a person’s movements, which can lead to loss of balance, difficulty walking, and problems with eye movement. In many cases, one of the first symptoms of PSP is a tendency to fall over easily (3). People may also experience changes in their cognition, behaviour, emotional regulation, and speech.

Some of the characteristic signs and symptoms of PSP include (3): 

• Impaired balance and mobility, including early falls.
• Cognitive changes such as apathy (lack of interest), impulsivity, depression or anxiety.
• Blurry or double vision.
• Trouble controlling eye and facial movements, which can cause reduced blinking, a ‘staring’ expression, difficulty focusing on objects, or difficulty looking up and down.
• Difficulty swallowing, especially with liquids (dysphagia).
• Muscle stiffness and loss of ability to move certain muscles resulting in slow movements (akinesia).
• Distorted, slow, or slurred speech (dysarthrophonia).
• Urinary urgency, incontinence, or constipation.
• Sleep difficulties.
• Change in food preferences.
• Weight loss (with possible malnutrition).
• Drooling.
• Problems with thinking and memory – particularly difficulty focussing on tasks and making complex decisions.

For many years there was a misconception that PSP is a type of ‘atypical Parkinson’s disease’. There is some overlap in symptoms, such as muscle stiffness and slow movements. Sometimes PSP is grouped with a few other rare diseases that include muscle stiffness and slowness as “atypical parkinsonism” however this describes the appearance of abnormal movements but is not a diagnosis. However, there are even more differences which are outlined in the table below and the pathology inside the brain is quite different. Recognising these differences is important so that patients receive the correct diagnosis and treatments.

Key differences in symptoms and signs in PSP and Parkinson’s disease (3)

*Bold text highlights the simplest quick-six to have in mind. 

Table adapted from J B Rowe et al, 2021, Progressive supranuclear palsy: diagnosis and management.

Diagnosis

Progressive supranuclear palsy is diagnosed with a neurological examination. Your neurologist will consider factors such as:

• Age when symptoms first started
• Medical history, including family history
• Assessment of symptoms
• Tests to exclude other diagnoses (i.e. Parkinson’s disease)

In general there is no singular test or neuroimaging scan used for the diagnosis of PSP. Tests are more often used to rule out other disorders, rather than confirming a PSP diagnosis. However, if an MRI is ordered, it may show shrinking of the brainstem. 

Patients often may be misdiagnosed, for example receiving a Parkinson’s disease (PD) diagnosis. There is also a subset of patients who may present with symptoms of frontotemporal dementia and are referred to dementia clinics. Fight Parkinson’s (an organisation that supports people with PD and related disorders) works with Dementia Australia on a couple of joint initiatives to support these people.

Treatment

There is no cure for progressive supranuclear palsy. Several medications can be helpful, as well as multidisciplinary care such as speech therapy or physiotherapy. As the disease progresses, patients may need a walker or other assistive devices. 

Medications

The medications recommended for a person with PSP will depend on their symptoms. PSP can increase your sensitivity to side effects (except for dopaminergic medications), so the general rule is to ‘start low and go slow’ (3). In fact, for many cognitive or behavioural symptoms, support, tolerance and environmental measures can be safer and more effective than medications (3).

Medications are used to help a patient manage symptoms that put them at risk or are particularly troublesome. Some medications that are used in PSP treatment include (1,3):

• Levodopa. While levodopa is much less effective in PSP compared to Parkinson’s disease, it can be helpful to begin with for managing motor symptoms in particular muscle stiffness and discomfort. For some people with PSP they can initially have a useful motor response to levodopa, but this lessens over 1-2 years.
• Amantadine. This is also used to help with motor symptoms in particular gait and balance problems. In general, younger patients (under 60) are more likely to report benefits, while people over 75 are more likely to experience significant side effects.
• Zolpidem. This is a GABA agonist used to improve motor function, sleep disturbances, speech and eye problems.
• SSRIs (antidepressants). Used to treat depression, anxiety, obsessive-compulsive behaviour and emotional lability. However, they may worsen apathy.
• Memantine. This is used to help people manage symptoms in a specific subtype of PSP which is characterised by speech difficulties (progressive non-fluent aphasia, or PNFA). 
• Botulinum toxin injection. Botulinum toxin injections to the pretarsal muscles can be effective to treat eyelid spasm and problems with keeping the eyes open, known as eyelid-opening apraxia. It is also used for significant neck pain and stiffness known as cervical dystonia. Occasionally it is used in more severe muscle spasms elsewhere in the limbs. 
• Artificial tears / eye drops. This is beneficial for eye irritation and dry eyes, which can occur from decreased blinking.
• Clonazepam. This is a benzodiazepine sometimes used for sleep problems and muscle stiffness, however it can also cause drowsiness.

This list is not exhaustive, but these are some of the more common medications used. Patient-centred treatment is important for people living with PSP, and each person’s symptoms and relevant medications will vary.

Non-drug support 

Non-drug support is equally as important as medication for managing PSP. Patients and families will require input from a diverse multidisciplinary team to help manage physical, emotional and mental symptoms (3). 

The role of your GP

A general practitioner who gets to know you well is extremely beneficial. This is a rare disease, and many GPs will not have seen it before. However, in addition to your neurologist or geriatrician, having a regular GP is an important part of your medical care. Firstly, most of the time treatments for more urgent symptoms such as urinary or chest infections are more promptly available from your GP. Secondly, coming to terms with the constant changes in your life and abilities due to a progressive neurological disease such as PSP can be difficult, and put strain on your relationships. Regular counselling with your GP is extremely beneficial in providing much needed support throughout this illness. It also ensures the rest of your health care needs are being managed.

Speech therapy

A speech therapist can teach safer swallowing techniques and advise on the need for dietary adjustment to minimise swallowing problems and maximise safe eating. These needs change regularly as the disease progresses, and review with a speech therapist at least twice a year is recommended. Occasionally a gastrostomy tube is discussed – it is important to discuss this thoroughly as it does not prevent aspiration risk and therefore pneumonia, but it may improve nutrition in some people. 

Speech therapy can also help with managing saliva and secretion problems. Saliva tends to become very thick and stringy due to the stiff facial muscles, and it pools in the mouth as swallowing is delayed. Most people with progressive supranuclear palsy will encounter secretion difficulties, causing coughing and sometimes choking sensations. The speech therapist will provide strategies such as humidification, using a nebulizer with saline to keep the airway moist, and other interventions to manage saliva and secretion.

The speech therapist can also offer the PSP patient alternative communication devices, such as pointing boards or computer-based systems. Audiobooks provide an alternative when reading is no longer possible.

Physiotherapy

Physiotherapy is extremely important to maintain physical strength as long as possible and minimise falls risk. This prolongs physical independence and improves ability for others to care for the person with PSP when they need assistance, and can reduce the risk of pneumonia. A weighted, 4-wheeled walker can help prevent falls and improve physical independence. Carers can obtain additional training from physiotherapists in helping the person with PSP to stand up and move around safely.

Dietician

A dietician can be very important in ensuring people with PSP have adequate nutrition. Due to the combination of swallowing problems and slowed hand movements many people with PSP find it more difficult to eat meals and may reduce their nutritional intake, leading to weight loss and in particular muscle loss, compounding their weakness. Ensuring adequate nutrition, particularly of proteins in the diet, is important to maintain muscle strength and ensure the body has sufficient energy to combat any infections such as pneumonia. These needs can change over the course of the disease and review over time is helpful. 

Other specialists & considerations

Other specialists could include an exercise physiologist, specialist nurse, occupational therapist, gastroenterology team, mental health worker, social worker, community pharmacist, or continence advisor. 

Caregivers can improve the safety of the person with PSP by keeping pathways in the home clear of objects such as toys, floor rugs, or low furniture that are difficult to see without looking down. An occupational therapist (OT) can advise on these and other home modifications such as rails, ramps and shower chairs to improve safety, comfort, and usability of the home environment. For example, an OT may assist in decluttering a home as the person may not be able to see low lying objects due to the upward gaze palsy.

Outlook

PSP gets progressively worse but is not itself directly life-threatening. It does, however, predispose patients to serious complications such as pneumonia secondary to difficulty in swallowing. The average prognosis after diagnosis sits between 5-9 years (4). The most common complications are choking and pneumonia, head injury and fractures caused by falls. The most common cause of death is pneumonia. 

Interventions such as PEG tubes and aggressive treatment of pneumonia can prolong life. This is a condition where establishing an advanced care plan (ACP) is important, and will have an influence on length of life. The ACP discussion needs to occur early due to the communication changes and possible cognitive changes – it can be very hard to assess cognition due the communication changes later in the disease. With good attention to medical and nutritional needs, however, most PSP patients live well into their 70s and beyond. 

Clinical trials have been undertaken of treatments which appeared to show benefit in the laboratory. So far none of these treatments have proven sufficiently beneficial in humans, and as a result are not available for treatment for this disease. However, others are in development and clinical trials of new treatments may be available for those who meet specific criteria. Information about these trials can be found by discussing this with your treating neurologist, patient support groups, and clinical trials registries.

Further information & support

Click here for the latest Australian research papers on Progressive Supranuclear Palsy.

In 2012, Dr Kelly Bertram was the recipient of Brain Foundation grant funding for research into Acoustic Neuroma – click for more.

Fight Parkinson’s
Fight Parkinson’s is a leading source of specialised health information, advice, and services. Through research, education, and support, they strive to improve the lives of people living with Parkinson’s or Atypical Parkinson’s (PSP, MSA and CBS).
Phone: 1800 644 189
www.fightparkinsons.org.au/atypical-parkinsons
www.fightparkinsons.org.au/i-am/psp-cbs-msa-treatment-professional-support-overview/ 

International Parkinson and Movement Disorder Society (MDS)
www.movementdisorders.org/ 

CurePSP (USA)
CurePSP has helpful web resources. However, please note they are an international organisation and references to medication or support programs might not be applicable in Australia.
https://www.psp.org/

PSP Association (UK)
PSP Association UK is another organisation with great information. However, please note they are an international organisation and references to medication or support programs might not be applicable in Australia.
https://www.pspassociation.org.uk/ 

References:

1. H Ling, 2015, Clinical Approach to Progressive Supranuclear Palsy. DOI: 10.14802/jmd.15060
2. N Giagkoua et al, 2019, Progressive supranuclear palsy. DOI: 10.1016/bs.irn.2019.10.013
3. J B Rowe et al, 2021, Progressive supranuclear palsy: diagnosis and management. DOI: 10.1136/practneurol-2020-002794
4. S A Glasmacher et al, 2017, Predictors of survival on Progressive supranuclear palsy and multiple system atrophy: a systemic review and meta-analysis. DOI: 10.1136/jnnp-2016-314956