Parkinson’s Disease Compared to Atypical Parkinsonism Disorders – Webinar Notes

Parkinson’s Disease Compared to Atypical Parkinsonism Disorders – Webinar Notes

In late July, PMD Alliance (pmdalliance.org) hosted a one-hour webinar with Irene Litvan, MD, movement disorder specialist at UCSD.  The title of the webinar was “Doc, why don’t I have PD?”  Dr. Litvan says that some of her patients ask her this, pointing out that they have slowness, stiffness, and tremor.  Her presentation focused on atypical parkinsonism disorders as a whole and the differences between Parkinson’s Disease (PD) and these atypicals.  Of all the atypical parkinsonism disorders, she spent the most time on progressive supranuclear palsy and multiple system atrophy, just a bit of time on Lewy body dementia, and almost no time on corticobasal degeneration.  The question-and-answer session included a lot of comments on PD.  We at Stanford Parkinson’s Community Outreach listened to the webinar and are sharing our notes. 

Dr. Litvan indicated there are several ways people can help:

  • Participate in research
  • Raise awareness
  • Educating others  (Lots of uninformed people think that a PD diagnosis is like a cancer diagnosis.)
  • Lobbying for research funding
  • Donating your brain, when the time comes.

Find an additional overview of the atypical parkinsonism disorders, further comparisons between PD and the atypicals, and detailed information on four of the atypical parkinsonism disorders on Brain Support Network.

Find detailed information about brain donation for PD and the atypical parkinsonism disorders on the Brain Support Network website.

Find a link to the webinar recording here.

My notes from the webinar and question-and-answer session are below.

Robin
parkinsons.stanford.edu

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Atypical Parkinsonism:  Doc, why don’t I have PD?

Webinar hosted by PMD Alliance

July 24, 2020

Notes by Robin Riddle, Stanford Parkinson’s Community Outreach
Host:  Indu Subramanian, MD, neurologist, UCLA
Speaker:  Irene Litvan, MD, neurologist, UCSD 

(The presentation begins about 6:30.  The slides begin at 7:30.)

Some patients ask:  “Why don’t I have PD?  I am slow, stiff, and have tremors, so why don’t I have PD?”

Outline of talk:  (Dr. Litvan calls these “Key Points”)
– definition of parkinsonism- classification of the parkinsonian disorders- definition of atypical parkinsonian disorders- differences between PD and atypical parkinsonian disorders

Parkinsonism:

  • MOST IMPORTANT FEATURE:  slowness and low amplitude (small steps, no arm movement)
  • stiffness OR tremor
  • postural and walking instability

Video:  man with tremor at rest but when he raises his arms, the tremor goes away

Video:  slow walking

Parkinsonism disorders all have a dopamine problem.  Substantia nigra produces dopamine that makes the motor circuits work.  Dopamine is like gas for a car.

DATscan can tell you if you have parkinsonism but not the particular disease.

Diseases with parkinsonism – two groups:

  1. Neurodegenerative:  PD and atypical parkinsonian disorders (PSP, MSA, CBD, DLB or LBD, familial).  Example of familial – frontotemporal dementia with parkinsonism (FTD-P).  [In a later slide, she lists two other familiarl atypical parkinsoan disorders – SCA-17 and FTD-TDP43.]
  2. Secondary
    Neurodegenerative – cells in the brain die and die much earlier than they should
    PSP, MSA, CBD, and DLB/LBD are sporadic.  No known cause.

What protein deposits in the brain:

  • In PD, MSA, and LBD/DLB, the protein is alpha-synuclein.
  • In PSP, CBD, and FTD-P-17, the protein is tau.

In research:

  • using CSF (spinal fluid) to find alpha-synuclein
  • treatments for targeting alpha-synuclein and for targeting tau

The slide refers to (but she won’t discuss now):

  • In SCA-17 (familial), the protein is ataxin.
  • In FTD-TDP43 (familial), the protein is Tatabox-binding protein.We don’t have experimental treatments for these proteins yet.

Atypical parkinsonism:

  • slowness PLUS
  • tremor OR rigidity OR postural and gait instability  (Usually it’s postural and gait instability)
  • AND problems that do not occur early in PD

    (APD = atypical parkinsonian disorders)

Differences:
PD:  excellent response to dopaminergic medication (levodopa or dopamine agonists)
APD:  lack of benefit to dopaminergic medication.  Initially, the person may respond minimally or mildly but we don’t see the kind of major benefit we see in PD.

PD:  May walk slowly but there are no problems with balance or falls for many, many years
APD:  Early balance problems and/or falls.  “Unexplained” falls.

Video:  lady with abnormal posture and poor balance.  Also, skin on foot with red color that goes away when leg is horizontal.  (This is a sign of autonomic dysfunction.)

PD:  Slow but otherwise walks normally
APD:  May walk like if “inebriated”
Video:  lady is unstable.  Legs are separated.  We don’t see this in PD.
Video (from Tolosa, 2007):  lady with PSP with early freezing.  Walking was her major problem.

[Dr. Litvan didn’t have a slide but said this:]
PD:  freezing does not usually occur early
APD:  freezing can occur early

PD:  slow progression.  Wheelchair needed when disease is quite advanced.  Or a patient may come to the clinic in a wheelchair but then they leave walking quite normally because of levodopa or other medication.
APD:  rapid progression.  Patients may come in to the clinic in a wheelchair with a fracture.

PD:  no problems with reading or moving eyes
APD:  problems moving the eyes up and down, difficulty reading

Video (from Steele):  vertical gaze palsy.  (In PSP, there are lesions above the nuclei of the nerves of the eyes, making both eyes not being able to move appropriately.  This is confirmed by moving the eyes up and down, through the doll’s head maneuver.)

Video (from Steele):  man not being able to look at his wristwatch on his lap, unless he moves his head.

PD:  slow, stiff, tremor when not doing anything
APD:  loss of ability to use hand or leg, limb; or there might be abnormal postures

Video:  policeman who lost ability to use his gun as his first symptom.  Then he developed abnormal movements – difficulty extending his arm; “jump” in arm; posture of fingers.  We don’t usually see these abnormal movements in PD. 

Clarification – in YOPD, we sometimes see these abnormal postures or dystonia (as with the policeman).  In YOPD, this improves with levodopa.

PD:  early-on normal cognition, depression, and anxiety
APD:  dementia, hallucinations, language problems

In PD, there can be some depression and anxiety.  Hallucinations are only with medications or some other reason. 

In APD, there can be hallucinations without any reason (such as medications).
Video:  man with LBD talking about hallucinations.  [Hard to hear.]

[Robin’s note: This slide contains an error.  In MSA and LBD, there can be RBD.  Dr. Litvan later admits she was thinking about PSP here.]
PD:  acting out dreams (RBD – REM behavior disorder)
APD:  not acting out dreams
Video:  man with RBD, which is an early sign of PD.

(30:00)
PSP – classic presentation:

  • early balance problems and falls (extremely common)* axial parkinsonism.  The axial areas (such as the neck and in the walking) is where the slowness and stiffness is.  In PD, by contract, the parkinsonism is in the limbs.
  • not benefiting from dopamine medication.  Why?  Because there are lesions in places other than the substantia nigra.  (Analogy – car might also need oil)
  • difficulty moving the eyes
  • early dysarthria (difficulty enunciating words)
  • may be dysphagia (swallowing problems)
  • frontal dementia or executive dysfunction is common.  (This area is the conductor of the brain.  Like an executive.  There are problems planning and multi-tasking.)

Video:  lady with PSP describing main problems.  First problem was falling.

(33:12)
MSA – two major presentations:

  • gradually progressive disorder
  • onset age 30 or later
  • autonomic failure:  low blood pressure when standing; urinary problems (urgency, frequency, incontinence, retention of urine); erectile dysfunction
    AND
  • parkinsonism (MSA-P) or cerebellar (MSA-C)
  • MSA-Parkinsonism includes slowness, stiffness, falls, balance problems, no benefit from dopamine medication

MSA-Cerebellar includes inebriated walk, incoordination, speech problem
Blood pressure problems can incude feeling like you are going to faint, fainting, pain in the back of the neck, and extreme fatigue.

Video:  man with MSA, describing blood pressure problems.
Video:  lady with MSA with speech problems
Video:  video of lady with MSA with incoordination

(36:45)
DLB – main clinical problems:

  • dementia
  • fluctuations:  day by day
  • visual hallucinations, not related to medications
  • parkinsonism
  • enacting dreams

(37:14)
Summary:

  • Parkinsonism is the combo of slowness, stiffness, tremor, and balance problems
  • Persons with atypical parkinsonian disorders have parkinsonism plus other problems that those with PD don’t have
  • Briefly pointed to the problems of person with PSP, MSA, and DLB

(38:09)
[Short summary by Indu Subramanian, MD.  Red flags, indicating the possibility of an atypical parkinsonism disorder, include poor response to medication, wide-based gait early on, eye movement problems (especially up or down) early on, dystonic hand or tight hand early on, early cognitive changes, early hallucinations (first couple of years), early falling, early speech problems, early swallowing problems.]

(40:17)
Q&A:

Q:  Dopamine-responsive dystonia – where does this fit?
A:  In PD, early on there can be postural problems (including abnormal posture of the leg or hand).  These problems can go away with medication, the majority of the time.  The person has many years doing well. 

By the way, Sinemet might last for less amount of time, after awhile.  This is not a problem of the disease.  It is a problem of medication.  Rytary can last five hours.  Sinemet always works; it might just happen for less amount of time.  [Dr. Litvan admits this didn’t respond to the question.]

Q:  Vascular parkinsonism – where does this fit?A:  This is a secondary disorder.  The cause was the multiple strokes that lead to parkinsonism.  The strokes were in the motor circuit.  Symptoms – wide-based gait (separated legs), postural instability, and problems are mostly in the legs.  The arms are pretty good.  (In PD, problems can be in both arms and legs.)  This is diagnosed based on history and brain MRI.  Treatment is mostly physical therapy.

Q:  What is “familial”?[Not answered]

Q:  Questioner pointed out that RBD can occur in MSA and LBD, despite what Dr. Litvan’s slide said.
A:  Yes, I got that wrong.  I was mostly thinking about PSP and CBD, where RBD does not occur.  In MSA and DLB, RBD occurs.
Q:  Sinemet – should people get off this?  Is there a placebo effect?
A:  When we give levodopa and someone does beautifully, this is because the person needs it for the motor circuit to work.  This is not a placebo effect.  It’s important to continue the medication.  This is a blessing — to do well with medication.

Q:  Biopsy – will they be helpful?
A:  Not yet.  We don’t have good ways to make a diagnosis. 

One issue is that there are different proteins in APD.  We are working on ligands for imaging for early diagnosis (example – ligand to bind to protein tau in PSP).  This is exploratory. 

Q:  What are the most exciting prospects for research for APD?
A:  We are starting to have treatments for these APDs. 

In PSP, there is only one protein.  It might be easier to find a solution for PSP as compared to Alzheimer’s (where there are two proteins – tau and beta-amyloid).  We just finished two studies that didn’t work.  But there’s a third one coming up that is an antibody treatment against tau.

(47:13)
[Dr. Litvan discusses animal models showing disease spreading to nearby cells, in both PD and PSP.  Antibodies can get rid of the abnormal proteins.  In the two studies that failed, the antibodies attacked a different part of the tau protein not responsible for spreading from one cell to another.]

(56:00)
Q by host: 
Can you give hope and a message of closure to the group?  How can activists who want to get involved in research improve their outcomes?
A:  Research is the best thing that can happen.  Particularly in PD, it’s the best time.  Why?  First, non-motor symptoms (RBD, depression, constipation, lack of smell) develop years before motor symptoms.  This shows what areas are affected.  There was a phenomenal study, using different PET scans, that showed that people who had RBD only had the same areas in the brain affected as those with PD, except the motor system.  When we look at pathology, the same thing happens.  Also evidence from physiology (mouse models) that the disease is spreading.  All the research is showing us a path.  What is the medication that is best?  Multiple opportunities.  One is antibodies.  Another is to act against the proteins that are abnormal.  And genetic ways are being experimented in animal models.  It’s extremely exciting.  All the data is in the same direction.  I never thought I would see all this.  I am very excited.


(1:00:20)
How can you help? 
Multiple ways.  Participate in research.  Spreading the voice about the disease.  Make people aware it exists.   An incredible number of people aren’t aware that these diseases exist.  And many people aren’t aware that PD can be treated.  People think that those with PD will be wheelchair bound in the first year.  When we give people a PD diagnosis, they feel like it’s a cancer diagnosis, with a short period of time to live and your life has come apart.  Fortunately there are several ways of improving that.  Educating is important.  Lobbying with your congressman, say we want more funding for our disease.  Donating the brain when the time comes is another way.  We can improve the care of these diseases and hopefully diagnose them early.  And hopefully we can find a treatment to slow the disease.  Or diagnose them so early so that you only have RBD.  That would be lovely.