On August 6 PMD Alliance hosted a webinar on Understanding Supranuclear Palsy (PSP). PSP is a neurodegenerative disease that can mimic Parkinson’s, but PSP is a distinct diagnosis with its own features and treatments. Amazingly, there are seven subtypes of PSP!
Movement disorders specialist, David Shprecher, DO, gave an overview of symptoms, the diagnostic process, complications of PSP, as well as current treatment options and the importance of participating in clinical trials (including brain donation) to advance understanding of PSP and develop new treatment options.
A recording of the webinar can be viewed on the PMD Alliance YouTube channel.
Symptoms of PSP overlap with those of Parkinson’s disease. For information on managing symptoms mentioned in this webinar, including anxiety, constipation, freezing of gait, incontinence, speech and swallowing issues check out the Symptoms section of the Stanford Parkinson’s website.
November is National Family Caregivers Month! For tips on caring for yourself while caring for someone with a parkinsonism disorder, check out the Stanford Parkinson’s Caregiver Corner.
On June 29, 2024 Stanford and Brain Support Network hosted a symposium on corticobasal degeneration (CBD) and PSP. Recordings of all the speakers are posted on this Brain Support Network webpage.
Brain Support Network also makes available this page of Top PSP Resources, which is also available in a PDF format for easy printing.
And now, on with my notes…
Denise
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“Understanding Progressive Supranuclear Palsy (PSP)”
Speaker: David Shprecher, DO, Banner Sun Health, Phoenix, AZ
Webinar Host: PMD Alliance
Webinar Date: August 6, 2024
Summary by: Denise Dagan, Stanford Parkinson’s Community Outreach Program
The comic actor, Dudley Moore, had Progressive Supranuclear Palsy (PSP). He is most famous for his lead role in the movie, Arthur, with Lisa Minelli. When announcing his diagnosis to the media he said, “I understand that one person in 100,000 suffers from the disease and I am also aware that there are 100,000 members of the Screen Actors Guild. I think, therefore, it is in some way considerate of me that I have taken on the disease for myself, thus protecting the remaining 99,999 members from this fate.”
Key Points in This Presentation
- PSP is the 2nd most common neurodegenerative cause of parkinsonism
- PSP diagnosis is based on symptoms. There is no specific test.
- Treatments ease the burden of symptoms
- Hope for the future through research
What is “parkinsonism?”
Any disorder in which a person demonstrates 2 of these 4 Cardinal Symptoms, including Parkinson’s Disease (PD) or Parkinson’s Plus Syndrome:
- Tremor
- Bradykinesia (slowness of movement)
- Rigidity (stiffness, or resistance of the limbs to passive movement)
- Postural instability (impaired balance)
Then the neurologist must determine the cause, which could be a medication side effect from mood stabilizers, antipsychotics (esp. Depakote) or damage from a toxin like manganese fumes from welding, etc. If they cannot pinpoint the cause, they will often diagnose garden variety Parkinson’s Disease (PD).
However, if more symptoms manifest in the 3-6 years following a PD or inconclusive ‘parkinsonism’ or Parkinson’s Plus diagnosis, a movement disorders specialist may be able to determine that the individual has an atypical parkinsonism.
Here is a list of the most commonly diagnosed forms of atypical parkinsonism and their distinguishing symptoms:
1. Dementia with Lewy Bodies (DLB)
Dementia
Hallucinations
Acting out dreams
Profound disorientation
Inattentiveness
2. Multiple System Atrophy (MSA)
Autonomic problems, including:
Incontinence
Fainting due to low blood pressure upon standing
Ataxia (coordination issues)
3. Corticobasal degeneration (CBD)
Apraxia (severe loss of hand control, especially on one side)
Dystonia (severe muscle cramping)
Alien limb syndrome (arm or leg moving of its own accord)
4. Progressive Supranuclear Palsy (PSP)
Recurrent severe falls
Trouble moving eyes vertically
Frontotemporal dementia (language problems, profound changes in behavior)
Red Flags – NOT Indicative of Parkinson’s Disease
Parkinson’s Disease and parkinsonism usually first manifest in the upper body. The notable exception being a resting tremor in one leg.
If someone has ONLY lower body symptoms a brain scan is warranted and may show the patient has either Vascular parkinsonism or Normal Pressure Hydrocephalus (NPH).
These two disorders are:
- NOT neurodegenerative
- Can co-exist with other conditions
- Require brain MRI or CT scan to diagnose
Key Features of Atypical Parkinsonian Disorders
At autopsy pathologists find proteins accumulated in the brains of people with parkinsonism disorders. The type of protein and where it accumulates in the brain determines whether the clinical diagnosis was correct.
- TAU protein is seen in PSP and CBD
- Alpha synuclein “Lewy bodies” is seen PD and DLB
- Alpha-synuclein is seen in MSA, particularly in glia cells
The Classic PSP Triad of Symptoms (98.5% of people with all 3 symptoms have PSP):
1. Vertical gaze problems (can’t look up and down)
2. Postural Instability (frequent falls due to impaired ability to react when balance is lost)
3. Atypical parkinsonism symptoms:
- more rigid in the neck than the arms
- similar symptoms on both sides of the body
- Levodopa response is poor (requires very high dose) or is less responsive over time
PSP Sub-Types
Richardson syndrome (PSP-RS)
* Only 30% of people exhibit classic Richardson PSP features (listed above), so people with PSP sub-types are often misdiagnosed.
* The rest will be able to follow a target with their eye up and down, but very slowly.
Parkinsonian variant (PSP-P)
* Initially looks like classic Parkinson’s Disease (PD)
* Additional symptoms manifest in the few years following PD diagnosis
* 30% of people with PSP
Progressive Gait Freezing (PSP-PGF)
* Starts with lower body problems, especially freezing of gait in first 3 years
* Unimproved by carbidopa-levodopa
* No vascular parkinsonism or NPH
* Other classic PSP symptoms can be very subtle (slow vertical eye movements and finger taps or open/closed hands)
Frontotemporal Dementia (PSP-F)
* Begins with language problems or changes in behavior, esp. impulsiveness, inappropriate social behaviors
* Dudley Moore was fired from a movie because he could not memorize his lines
Postural instability predominant (PSP-PI)
Corticobasal syndrome (PSP-CBS)
Speech language predominant (PSP-SL)
Diagnosis of PSP (Guidelines established in 2017)
Complex guidelines help neurologists (especially movement disorders specialists) to rule out Probable vs Possible diagnoses in order to increase confidence that everything has been considered and the correct diagnosis has been made. Includes observation of characteristic features and supportive tests.
Observation of Characteristic Features:
Vertical eye movement abnormalities
* Does the patient have difficulty looking up/down
* Can the patient follow two targets rapidly
* If you’re falling all the time and the neurologist doesn’t even look at your eye movements, get a second opinion. They are not doing a thorough enough exam.
Parkinsonism
* Can be subtle
* May be classic parkinsonian shuffling BUT may also be hyper erect and very stiff and fall frequently, especially when turning
Postural instability (severe)
* Frequent falls, especially when turning
* Freezing of gait, stutter step or stuck in place
Frontotemporal dementia type cognitive impairment
* Language issues – difficulty understanding, forming words and sentences
* Behavioral changes – impulsivity, inappropriate social behaviors
Supportive Tests:
Imaging is NEVER a substitute for a very detailed physical exam and history.
MRI or CT scan
* May show characteristic features of PSP (“Morning glory sign”) or MSA
* “Morning glory sign” shaped like a morning glory flower in the midbrain
* May raise concern for normal pressure hydrocephalus (NPH) or vascular parkinsonism
* Can help determine if there is more than one cause of parkinsonism symptoms
Syn One Biopsy test
* For Parkinson’s Disease ONLY. No studies on Syn One test for PSP.
* Positive test does NOT rule out PSP (upon autopsy, 10% of people over age 80 who were diagnosed with PD also had signs of PSP in their brain)
* Negative test may help improve diagnostic confidence in less common presentations of PSP
DaTscan
* Negative test may suggest other motor neuron disease, like Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, or Primary Lateral Sclerosis (PLS), especially with speech slurring
* Not always interpreted correctly
Common Symptoms of PSP
Cognitive (frontotemporal dementia)
Blepharospasm / eyelid opening apraxia (difficulty keeping eyes open)
Behavioral
* Involuntary Emotional Expression / Pseudobulbar Affect (laughing or crying at inappropriate times). Loved ones may assume depression. Doesn’t respond to antidepressants but there are medications that can help
* Anxiety – antidepressants can help
Insomnia, Restless Leg Syndrome (RLS)
* Medications can help RLS
Swallowing problems
* Caregivers should learn the Heimlich maneuver for choking
* Patients should learn to tuck chin to chest when swallowing thin liquids to prevent aspiration
thicken liquids to avoid aspiration pneumonia
Speech problems (projection and enunciation), language (word-finding)
* Need a speech language pathologist (SLP) familiar with aphasia/stroke. SLPs can also help with swallowing issues
Constipation, bladder incontinence
PSP Prognosis
Atypical parkinsonian disorders progress much faster than PD, which has a near-normal life expectancy. People with PSP and their care partners may expect:
Wheelchair dependency due to repeated falls in 3-4 years. Not so much because they can’t walk but because freezing and falling has the high potential for injury. People with PSP tend to be impulsive and forget to use their assistive device. Constant supervision and walking assistance can be taxing for caregivers.
Severe swallowing problems in 5-6 yrs
Incontinence by 6 yrs
Severe cognitive impairment by 6 yrs
Lifespan for classic Richardson syndrome (PSP-RS) from start of symptoms averages 5-8 yrs
Some people with the parkinsonian (PSP-P) and gait freezing (PSP-PGF) variants may live much longer
Standard PSP Treatments
Parkinsonism
* Carbidopa-levodopa (1200 mg per day (or much higher, 1600-2000mg/day, to max tolerated dose)
* May improve fine motor skills in the hands and gait freezing
* Does NOT restore postural reflexes (catching yourself when you fall)
Gait Freezing
* Some people respond to Amantadine
* Try if the person does not respond to carbidopa-levodopa or has stomach upset when taking carbidopa-levodopa
Postural Instability
* Physical therapy (PT), although limited duration of benefit
* Ensure the PT is clear on what the goal is:
- reducing risk of injury due to falls
- balance exercise to slow decline of instability
- freezing of gait
If the PT is not clear that reducing/overcoming freezing of gait is a goal, they may discontinue PT because the patient stopped making progress with balance/instability issue.
Not every PT knows how to treat freezing of gait. [Look for a neuro-PT or one trained in LSVT BIG
The Stanford Parkinson’s website has a list of PTs who specialize in treating people with parkinsonism disorders on the San Francisco Peninsula and in the South Bay at: stanford.edu/parkinsons/northern-california-resources/pt.html]
Involuntary Emotional Expression
Treatment is optional, but Dr. Shprecher recommends treating if emotional outbursts interfere with eating, or other activities
- Nuedexta (dextromethorphan + quinidine), titrate up to 1 pill 2x daily
- antidepressants may help
Blepharospasm (involuntary eye closing) and/or Excess saliva
* Botulinum toxin injections is the recommended treatment for both (lasts 3-4 months)
* Recommended for excess saliva to prevent aspiration during sleep, which can lead to pneumonia. If left untreated, aspiration pneumonia is fatal.
* Botulinum toxin is not effective to treat head dropping forward because where the injection must be done for this can impair swallowing
Insomnia
* Antidepressants are often used off-label to treat insomnia because sedating mediations can worsen balance or impulsiveness during the day (Trazodone, mirtazapine).
Bladder incontinence
* Several medication options, but AVOID oxybutynin (worsens cognitive symptoms)
* Treatment of bladder issues may require communication and cooperation between several people on your medical team (neurologist, urologist, pelvic floor physical therapist, etc.)
Restless Leg Syndrome (RLS)
* First line medications – gabapentin, Horizant (gabapentin enacarbil), pregabalin,
* Second line medications (more side effect risks) – ropinirole, pramipexole, Neupro (rotigotine)
Important Care Considerations
Movement Disorders Specialist (MDS)
More experienced with rare neurodegenerative disorders so better to get an accurate diagnosis and follow symptoms than a general neurologist or primary care doctor
Telemedicine is fine for most check-ups
Synapticure MDSs are licensed in all 50 states and will communicate with your neurologist so you can see a movement disorders specialist when traveling anywhere in the US.
Multidisciplinary care
At the end of each appointment remind your care providers to share notes with all your other care providers. Example: your neurologist should copy your primary care provider, and other specialists so everyone is on the same page.
Advance care planning and caregiver burden
- Consult with a social worker to ensure everyone knows what your end-of-life care wishes are, especially with regard to:
- Feeding tube when losing weight or unable to swallow
- Emergency room visits for every fall
- Antibiotics for every infection
- Create a back-up plan in case something happens to the primary caregiver’s health or if they become overwhelmed
- How will caregivers provide 24/7 supervision to prevent falls? Recruit family and friends, hire in-home help, or move to a care facility?
When to consider genetic testing
PSP does not usually run in families. However, Dr. Shprecher would strongly recommend genetic testing if you have…
- First degree relative with motor neuron disease
- C9orf72 expansion gene tends to cause ALS, PSP, and FTD
- First degree relative with PSP may have these gene mutations
- Progranulin, MAPT, LRRK2
Genetic testing is NOT covered by Medicare. However, you may want to pay for it if you have descendants and want them to know what you really had.
You must do genetic testing before the person with a neurodegenerative disorder dies in order to benefit from future medical advances that treat specific inherited genetic profiles.
Hope Through Research
- Earlier, more accurate diagnosis
- Understanding the cause of PSP
- Better treatments for symptoms
- Efforts at slowing the disease
Genetic Discoveries from PSP Brain Donation
Recent studies based on brain donations found slight increases in risk from a few other genes. Not everyone with PSP has these gene mutations but people with these gene mutations are more likely to have PSP.
- Syntaxin-6, EIF2AK3, and MOBP
- MOBP (myelin associated oligodendrocyte protein) linked to CBD and PSP
- N-acetyltransferase 2 rapid acetylator phenotype is associated with PSP, suggesting it may be responsible for activation of a xenobiotic whose metabolite is neurotoxic.
- If someone has this gene mutation, toxins in the environment may be converted into something that causes PSP. As yet, researchers don’t know what those toxins are or what gene variations can lead to PSP.
Study to Improve Diagnosis of PSP and Alzheimer’s
- PI-2620 binds to the tau protein, which lights up in PET scan of the brain
- One pattern may indicate Alzheimer’s, while another pattern may indicate PSP
- Particularly useful to accurately diagnose classic Richardson syndrome (PSP-RS)
- People with any advanced neurodegenerative illness can volunteer for the Life Molecular Imaging study
Treatments that Did NOT Slow Progression of PSP
- Antioxidants
- coenzyme Q10, rasagiline, RT-001
- Microtubule stabilizer davunetide
- Anti-tau antibodies (intended to bind to tau protein, preventing it from spreading one brain cell to another)
- BIIB092, ABBV-8E12
Studies of Treatments Designed to Slow Progression – Now Enrolling!!!
AMX0035 (sodium phenybutyrate/atrurusodiol)
Targets endoplasmic reticulum stress and mitrochondrial dysfunction
Amylyx, pharmaceutical company (amylyxpsptrial.com)
FNP-223 (ASN90)
Aims to block tau aggregation
Ferrer, pharmaceutical company
Enroll through UCSF
Look up “PROSPER trial +PSP” online to find other participating institutions
Additional trials may be listed soon on clinicaltrials.gov
Observational PSP Research
Anyone with atypical parkinsonism can sign up for the CurePSP brain donation program – psp.org/brain-donation-program
[If you have difficulty finding navigating the CurePSP website or brain donation process, Brain Support Network (BSN) is a non-profit that walks families through the process one step at a time. BSN asks for a one-time, tax-deductible donation of $750, which can be made after the person making the brain donation passes.]
Because unusual presentations of PSP can only be confirmed with an autopsy
This program gives your family a definite answer of what you had
Genetic research into the cause of PSP can be done from this program
Key Points / Summary
PSP is a prime-of-life illness that is likely under diagnosed.
A recent paper estimated 700 per 100,000, rather than the commonly used number of 10 in 100,000.
PSP diagnosis requires expert history and an exam by a movement disorders specialist (and may require autopsy to confirm). There is no diagnostic test at this time.
Multidisciplinary care and advanced planning can ease the burden of PSP. Be sure to remind every practitioner on your care team to copy all others on their notes after every office visit, so everyone is on the same page.
There is hope for the future through research. You are unlikely to benefit from PSP research, but participation will benefit your children and grandchildren.
Question & Answers
Question: When you’re talking about gait differences and falls in someone with PSP. How does that present?
Answer: It is not always clear, but it seems to be impaired postural reflex, meaning the body is unable to rebalance and prevent falling when you lose your footing. Because of this, someone with PSP should always have someone spot them when sitting (to slow their decent onto the chair) and while walking.
If someone has severe gait freezing, they may freeze (especially when turning) which leads to a fall. Again, when frozen the body is unable to rebalance or catch themselves and prevent falling.
Question: There is gait freezing in Parkinson’s Disease (PD). Is how the disease initially presents how you distinguish between PD and PSP?
Answer: Parkinson’s Disease is a diagnosis of exclusion. If you have severe gait freezing with falls (that does NOT go away completely with the use of carbidopa-levodopa) in the first three years of illness, you likely have an atypical parkinsonian disorder. You should see an experienced neurologist/movement disorders specialist to determine which one.
There is a rare variant of PSP where severe gait freezing is the initial symptom and over time more PSP symptoms will emerge, like up/down slow eye movements and slow movements.
Question: How does dementia in PSP present as compared to Parkinson’s Disease (PD) or Lewy Body Dementia (LBD)?
Answer: In the beginning most people with PSP don’t have cognitive impairment or dementia. If you ask them, they may have difficulty with language, executive functioning or multi-tasking. A subset may have problems with changes of behavior or impulse control.
PSP is not a memory problem for most people so memory enhancers for Alzheimer’s or PD are generally not effective (Aricept, Namenda).
It is usually in the late stages that cognitive issues of PSP interfere. What can be frustrating is slow processing speed, which can make it frustrating to have a conversation. That’s when a speech-language pathologist (SLP) can give you strategies to communicate common phrases. Remember, you want a SLP with experience treating stroke/aphasia.
Question: What do you do as a treating physician help families navigate the fast progression of PSP, especially with respect to accepting the diagnosis, getting affairs in order, and plugging into physical, occupational, and speech therapies?
Answer: Social workers are the best resources for families. They can help families process the diagnosis, find needed resources at each stage of progression, and get their affairs in order. Some of this information is also available through support groups.
Palliative care programs typically include a social worker on the care team, but palliative care is not universally available in the US. Telemedicine extends the availability of palliative care.
Question: What is the potential for these new PSP drugs (in clinical trials) to help find a drug to slow or stop Parkinson’s?
Answer: We don’t know of any drug that slows progression of any neurodegenerative disorders, so participating in a research study will probably not benefit you directly but will benefit next generations.
Question: Is there any test for tau in blood and/or cerebral spinal fluid that will help make the diagnosis of PSP?
Answer: There’s a lot of research happening but nothing is ready for prime time. There may be a spinal test for synuclein protein soon.
Question: A speech pathologist listener says oral care is very important for people with PSP. Speech exercises help the muscles used to cough. Please comment.
Answer: PSP care is multidisciplinary. Allied health professionals (physical, occupational, and speech therapies) are very important to the team.