CurePSP and the Mayo Clinic co-hosted a conference in late June 2018
on progressive supranuclear palsy, corticobasal degeneration, and
multiple system atrophy. Here’s a link to the video recordings of
CurePSP and the Mayo Clinic co-hosted a conference in late June 2018
on progressive supranuclear palsy, corticobasal degeneration, and
multiple system atrophy. Here’s a link to the video recordings of
Update on 6/11/18: Unfortunately this webinar is now cancelled.
Brain Support Network group member Steven Russell shared with me today info on an upcoming webinar, which will give an overview of all four of the atypical parkinsonism disorders — MSA, LBD, PSP, and CBD. Details are:
What If It’s NOT Parkinson’s?
In this webinar, Dr. Mihaela Alexander, Colorado Neurodiagnostics, will discuss atypical parkinsonisms such as multiple system atrophy and Lewy body dementia, among others (PSP, CBD). Dr. Alexander will cover what we know about these conditions and what treatments are available for each condition.
Tuesday, June 12
10-11am CA time
Parkinson Association of the Rockies, Denver, parkinsonrockies.org
General Information: (same as what is above)
Northern California-based Family Caregiver Alliance (caregiver.org) is
organizing a free educational program called SHARE.
The care receiver (person with a neurological diagnosis) must:
– Be over age 60
– Be living at home in the San Francisco Bay Area
– Have intact cognitive abilities – NO dementia
– Not be in the terminal stage of their disease
The caregiver will receive:
– 6 in-person home visits
– Learn effective communication skills
– Learn to reduce stress
– Learn to promote health
– Learn about long-term care management (make the most out of today
while planning for tomorrow)
If this is of interest, contact Michelle Venegas (415-434-3388, x323,
As 2017 ticks down, we hope you enjoy some quality-time with family and friends. We wanted to share our results for 2017. Plus, this is a great time to make a charitable contribution as other generous donors are doubling your contribution.
Brain Support Network (BSN) continues to pursue its three missions:
(1) create and disseminate information on LBD, PSP, MSA, and CBD to members (You are one of 450 Northern Californians on our network’s email list.)
(2) coordinate the local caregiver support group in San Mateo
(3) help any family with brain donation.
We (BSN volunteers and part-time employees) have kept busy in 2017:
Brain Support Network (BSN) continues to pursue its three missions:
(1) create and disseminate information on LBD, PSP, MSA, and CBD to members
(2) help any family with brain donation
(3) coordinate the local caregiver support group in Northern California
We (BSN volunteers and part-time employees) have kept busy in 2017:
* We sent out over 250 email updates, most of which focused on one of four specific disorders: LBD (Lewy body dementia), PSP (progressive supranuclear palsy), MSA (multiple system atrophy), and CBD (corticobasal degeneration). Many emails relate to caregiving and dementia caregiving.
* We published over 600 Facebook posts on similar subjects (because some people prefer Facebook).
* We served as a clearinghouse of information and support for network members.
* We have kept our web site relevant and up to date (e.g. our “Top Resources” lists for the four primary disorders and our blog).
* We organized 94 brain donations (a new record for BSN), most of which were delivered to the Mayo Clinic in Jacksonville. (Of course the year isn’t quite finished.)
* We hosted our largest-ever “Research Update and Practical Conference on PSP/CBD” in cooperation with the UCSF Memory and Aging Center on October 28, 2017, in San Mateo. Conference video and handouts are available.
This is the time of year when we ask you for assistance.
Five long-time support group members and two long-time BSN benefactors have offered a “challenge grant” to network members. Your charitable contributions through December 31st will be matched up to $8,000. Please help us take advantage of this opportunity and help make possible our efforts for the coming year.
If you mail a check, please write “match” on the memo line along with the name of the family member or friend that you are honoring or remembering. Or, enclose a note with that information. Make checks payable to “Brain Support Network,” and mail to BSN, PO Box 7264, Menlo Park, CA 94026. To count towards the challenge donation, checks should be dated and postmarked by December 31, 2017, Your check does *not* need to be received by this date.
If you make an online contribution (via credit card), please write the name of your family member/friend after selecting “in honor of” or “in memory of.” Please append “/Match” to the name of the person. To count towards the challenge donation, online contributions should be completed by Sunday, December 31, at 11:59pm California time.
Brain Support Network is recognized by the IRS as a 501(c)(3) tax-exempt charity and your donations are deductible to the extent allowed by law. Please know that any amount—$25, $50, $100, $250, $500, or more—is appreciated! Thank you for supporting our three missions!
Happy 2018 to you and your families!
Brain Support Network CEO
A local support group member whose loved one was involved in this TPI 287 trial at UCSF contacted me a couple of weeks ago to say that she had learned that the trial was not successful. I haven’t been able to find any independently-written article [see updated below!] on the study results (and, of course, clinicaltrials.gov shows nothing) but there is this pharmaceutical company press release.
The TPI 287 study was discussed by Adam Boxer, MD, UCSF at our recent PSP/CBD conference. This was a phase 1 study, which has a safety focus. Researchers are also trying to learn something about efficacy during these studies but that’s not the main point. In the study, 14 patients with PSP and 30 patients with CBS were included. 32 received the drug and 12 received the placebo.
This seems to be the crux of the problem — “Interestingly, patients treated with TPI 287 performed worse on the [Clinical Dementia Rating] assessment vs. placebo after 12 weeks.”
Update: A member of our email list forwarded me that independent write-up I was looking for on TPI 287; it’s on Alzforum. Just as the group member said, the trial had negative results. In addition to the worsening in the dementia rating scale (mentioned earlier today), there was also a worsening of falls in CBD and PSP patients. The study was also conducted of the same compound, TPI 287, in Alzheimer’s Disease. The experimental drug was not safe in AD patients at high doses. An excerpt from the Alzforum summary is below.
At Least We Know These Don’t Work: Negative Trials at CTAD
15 Dec 2017
Adam Boxer, University of California, San Francisco, presented his center’s Phase 1 trial of TP1 287. Also known as abeotaxane, this small-molecule taxol derivative stabilizes microtubules. TPI 287 accumulates in the brain, and has been tested primarily to treat central nervous system tumors. Its application to tauopathies grew out of work showing beneficial effects of the microtubule stabilizer epothilone D in tau transgenic mice (Zhang et al., 2012). Testing of epothilone D in AD patients started in 2012 but was discontinued for lack of efficacy.
Boxer’s group examined the safety and tolerability of TP1 287 in 44 people with the primary four-repeat tauopathies cortical basal degeneration (CBD) or progressive supranuclear palsy (PSP), and in 33 people with AD. Participants received abeotaxane by intravenous infusion once every three weeks for nine weeks, with an option for open-label extension up to three months.
In recruiting for the CBD cohort, Boxer screened with amyloid PET to exclude people with AD and to limit the treatment group to people with pure tau pathology. Of 55 diagnosed with CBD, Boxer excluded seven based on positive amyloid scans. He also used CSF biomarkers to confirm diagnoses: AD patients had lower Aβ42 and higher total tau and phospho-tau levels than CBD/PSP group members, who showed elevations in neurofilament and a higher neurofilament light (NfL)/phospho-tau ratio than the AD group.
Participants received tailored doses of 2, 6.3, or 20 mg/meter2 TPI 287, or placebo.
AD patients tolerated the treatment poorly. Boxer told the CTAD audience that he had to stop the high-dose arm because two participants suffered anaphylactoid hypersensitivity reactions, most likely to the diluent for the active compound. In all, seven people in the AD group discontinued treatment. Curiously, the CBD/PSP group tolerated the drug well, even at the highest dose. They suffered no hypersensitivity reactions, and most participants stuck with the trial even through the open-label extension. However, in CBD and PSP patients, the drug caused more falls, a serious concern.
On the exploratory cognitive endpoints, the researchers saw a hint of stabilization of MMSE scores in the AD group, but no change in the ADAS-Cog, and the CBD/PSP cohort had a dose-related worsening on the Clinical Dementia Rating-Sum of Boxes at three months.
Boxer has no future plans for the drug, except to complete the analyses of pharmacokinetics and MRIs. He told Alzforum that investigators learned a lot from the trial. “It shows the importance of testing potential treatments in different tauopathies,” he said. “Animal models don’t tell the whole story, and we have to look at different conditions in humans,” he said.
Janet Edmunson, author of the book Finding Meaning with Charles, has given permission to share an excerpt on acceptance and denial. The “Charles” in the book’s title is Janet’s late husband. He was diagnosed during life with progressive supranuclear palsy, and with corticobasal degeneration upon death. We have many copies of the wonderful book to share within our local support group.
Though the book is primarily for caregivers, I think those with a neurological diagnosis can find great benefit from it. And the book has very few PSP-specific or CBD-specific details so it can be appreciated by everyone.
Check out Janet’s website (janetedmunson.com) at for details on her occasional webinars for caregivers and for her “positive affirmations” emails. Her book can be purchased at Amazon.com.
Finding Meaning with Charles
by Janet Edmunson
Available in paperback, audiobook and e-book formats on Amazon.com
It wasn’t until about the third year of Charles’s disease that the Serenity Prayer had its greatest impact on me. But I have always loved it, and it means the most to me when I am going through tough times: “ . . . grant me the serenity to accept the things I cannot change, courage to change the things I can, and wisdom to know the difference.”
I have really latched onto the concept of “accepting the things I cannot change.” Though we tried to fight it, Charles’s disease was going to take away his abilities, and eventually, his life. Our choice was to accept that or deny it.
I don’t know for sure what Charles’s choice was. He was determined not to let the disease change his life and goals. He tried hard to keep contributing as best he could. That was how Charles tackled everything in life. He denied the obstacle and set out to conquer it. He wouldn’t succumb. He fought all the way to the end.
Is that acceptance or denial?
I, however, consciously chose to accept it and make the most of it.
My greatest learning through this experience came when Charles and I attended the Mind/Body Medical Institute program which, at the time, was held at Beth Israel Deaconess Hospital in Boston. The instructor, Peg, talked about acceptance, explaining that the way to accept the things that we have no control over, such as an illness, is to make meaning out of it. Wow! Make meaning out of it! Her explanation suddenly allowed me to consciously look at what Charles and I were going through and identify where it helped us grow and where it allowed us to have an impact on others that we wouldn’t have had without the adversity of his disease.
Taking a proactive approach to making meaning out of our situation helped me to positively focus on the opportunities and not plunge into depression. I was determined to help Charles reach whatever potential his life could give. And I was amazed to see how Charles became even more influential – even after he could no longer talk. As a caregiver, I found it important to focus on this greater purpose. My goal for caregiving went beyond making sure Charles was safe and physically cared for. I wanted to ensure that he still lived life to the fullest whatever degree the disease would allow.
Accepting Charles’s disease and making meaning out of it didn’t mean that we didn’t feel pain. Coping with this type of degeneration was difficult physically and emotionally for Charles, the person with the disease, as well as for me, the caregiver. We faced many trials – some successfully, others not. But we both became better people through experiencing his disease.
Scott Peck starts his book, The Road Less Traveled, with the sentence “Life is difficult.” He goes on to explain that once we accept this, we can begin to make the most of life. Charles and I had discussed this concept a number of times when we faced problems at work or with other people. The misfortune of his disease forced us to face our greatest life difficulty, truly testing our ability to accept adversity and then move on.
I don’t know of anyone who expressed this thought better than Viktor Frankl in his book, Man’s Search for Meaning. Frankl survived the atrocities and indignities of a concentration camp in World War II.
He realized there that to renew our inner strength, we need to have a future goal. He quoted Nietzsche’s words, “He who has a why to live for can bear with almost any how.” I found that “finding meaning” is a way to define the why. The act of looking for and finding meaning in Charles’s disease focused and empowered me.
This post may be of interest to those dealing with the non-Alzheimer’s dementias in our network — Lewy body dementia, progressive supranuclear palsy, and corticobasal degeneration. (PSP and CBD do not always present with dementia.) Lewy body dementia is specifically mentioned in this interview.
Being Patient (beingpatient.com) is an Alzheimer’s news website. In July 2017, the news organization interviewed Dr. Marwan Sabbagh of the Barrow Neurological Institute in Phoenix, AZ. In the interview, Dr. Sabbagh describes the challenge in making a dementia diagnosis. He describes some improvements that could be made in the standard practice of diagnosing dementia.
Dr. Sabbagh says: “Pathologically pure Alzheimer’s without any other pathology is quite rare. It’s only like 33 to 40 percent. Most Alzheimer’s is mixed with something else – hippocampal sclerosis, vascular change, argyrophilic grain [disease], or Lewy body. Pure disease of any type is quite uncommon. A lot of people have overlap but they look typically like Alzheimer’s dementia, so the clinical presentation and the pathological presentation don’t always align as much as you would think they would. … As a clinician, I ask ‘What’s the clinical syndrome and how do we go about teasing it out to make sure we have the correct diagnosis?’ … People are grossly misdiagnosed. Lewy body is not detected often. Most of the other dementias are completely missed.”
The video interview is just under 12 minutes. Excerpts from the interview are copied below. (The “transcript” doesn’t include all of the interview.)
Is It Alzheimer’s or Another Type of Dementia? How the Experts Make a Diagnosis
Interview with Marwan Sabbagh, MD
Being Patient (beingpatient.com)
July 26, 2017
Although the National Institute of Health has published medical reports on guidelines to diagnose Alzheimer’s disease, it can sometimes take years for patients to get an accurate diagnosis from their primary care doctors. Expensive scans or lumbar puncture tests are one way to confirm the presence of beta amyloid plaques or tau tangles in the brain, but those aren’t an option for many patients due to their high cost. Being Patient asked Marwan Sabbagh, a leading researcher on the diagnosis of Alzheimer’s disease at the Barrow Neurological Institute about the best way to determine if a patient is suffering from mild cognitive impairment or dementia.
Being Patient: There’s a lot of confusion over how you get diagnosed for Alzheimer’s disease. Previously, we’ve been told that a PET (positron emission tomography) scan or a spinal tap are the only conclusive ways to figure out whether there are plaques and tangles in your brain. Why is there so much confusion over diagnosing dementia?
Marwan Sabbagh: The historical, medical practice in the United States has been to take a diagnosis of exclusion. You have a medical history, a neurological exam, cognitive impairment, historically, and then you get a MRI to exclude brain tumors, masses, hydrocephalus, or stroke. You get a thyroid [exam] to exclude thyroid problems, and you get a B12 level [test] to exclude deficiencies in B12. The problem has been a diagnosis of exclusion is a grossly inaccurate approach and the diagnostic accuracy, at best, is 75 percent.
Being Patient: What are some of the essential questions you need to ask and what are some of the essential things that primary care doctors should be looking at in order to determine whether or not this is Alzheimer’s dementia?
Marwan Sabbagh: I think doctors know how to do a mini-mental state exam – a MOCA, Montreal Cognitive Assessment. They know what to do but they don’t know what questions to ask on the front end, so I’ve been proposing a restructuring of the initial side of the consultation. There are structured interviews that are available now – the AD8, the AQ and the IQ code. These are caregiver informant-based interviews. Do they have this?Do they have that? Are they doing this? [These questions] inform the provider to say, “It’s time to look further.”
The second thing I propose is that we need to look at aggregate risk analysis. There are now ways to say that the probability of Alzheimer dementia is very high if you are age 85, have a family history, female gender, hypertension and diabetes. You can come up with a score that says the probability of Alzheimer dementia is very high.
Being Patient: I want to talk a little bit now about different types of dementia and diagnosis – a number of patients say they were misdiagnosed and a pathologist we spoke to said that, through autopsy, he found that the majority of cases in his practice are being misdiagnosed. How do you tell if it is Alzheimer’s or another type of dementia?
Marwan Sabbagh: Pathologically pure Alzheimer’s without any other pathology is quite rare. It’s only like 33 to 40 percent. Most Alzheimer’s is mixed with something else – hippocampal sclerosis, vascular change, argyrophilic grain (disease) or Lewy body. Pure disease of any type is quite uncommon. A lot of people have overlap but they look typically like Alzheimer’s dementia, so the clinical presentation and the pathological presentation don’t always align as much as you would think they would.
As a clinician, I ask “What’s the clinical syndrome and how do we go about teasing it out to make sure we have the correct diagnosis?” You are absolutely right. People are grossly misdiagnosed. Lewy body is not detected often. Most of the other dementias are completely missed.
Being Patient: Does it matter to the patient in the end in terms of how they’re dealing, and coping, and engaging in maybe lifestyle treatments or medication?
Marwan Sabbagh: It does. It matters a lot. The reason it matters is lifestyle modifications, which are probably very good for brain wellness and prevention strategies in the Alzheimer’s spectrum from pre-symptomatic to the full dementia probably do not have as much data to support the recommendations in other dementias. Flatly, I don’t think there’s any shred of evidence that lifestyle recommendations would help another dementia like Lewy Body or frontotemporal dementia.
Being Patient: Is there a difference in diagnosing early onset versus dementia as Alzheimer’s in an elderly patient?
Marwan Sabbagh: In the way I approach it, yes. Most commonly, if it were a young person, early onset, I would do a spinal tap as my CSF (cerebrospinal fluid) confirmation to confirm the diagnosis. I tend to be a little bit more aggressive and invasive in what I do to diagnose my patients. Older patients, I might get a PET scan and, if it’s approved, I might get neuropsychological testing. I might get an ApoE genotype.
Being Patient: So many people now are impacted by this disease, a lot who are the children of a parent or a grandparent, and they want to know what are the early signs that they should look out for?
Marwan Sabbagh: You never misplaced things, now you’re misplacing things from time to time. You’re telling something repeatedly and you never did that before. These are the kinds of very subtle, very beginning things that would say [it’s] time to get an evaluation. Especially if there’s a risk.
Being Patient: There are people who carry ApoE4, who have both one variant and are homozygous, and there are people who don’t, who end up getting Alzheimer’s. How much should that genetic profile enter into diagnosis?
Marwan Sabbagh: That’s controversial and I’m sure you’ve had different opinions from different doctors so I’m going to give you my perspective. I tend to be on the more progressive side of the discussion. In the clinical evaluation of my patients with mild cognitive impairment (MCI) due to Alzheimer’s or dementia due to Alzheimer’s, I frequently order an ApoE genotype. If they’re an ApoE4 carrier in the setting of MCI or dementia due to Alzheimer’s then the probability of Alzheimer’s pathology in the mix is very high.
I never order it for people who are asymptomatic, even if they have a family history. I agree with many in the field that it’s not inherently a diagnostic, it is simply a risk factor, but it’s a very rich risk factor because, if you are an ApoE4 carrier, the probability of having Alzheimer’s amyloid on your PET scan is very high. Some people are even proposing the idea of using it as a screening tool. Has this become common practice? The answer is absolutely no.
Being Patient: Once you give someone a diagnosis of Alzheimer’s dementia, do you believe the earlier you catch it the better off you are?
Marwan Sabbagh: I come from the school of thought that Alzheimer’s is a treatable disease. I am aggressive in treating my patients. I am proactive in addressing their healthcare needs, their family needs, their medication needs, their legal needs, and offering clinical trials as an added value to our clinical practice. Patients want that information. They’re seeking it. They’ve craving it. They want it from a credible source.
This webinar from the Michael J. Fox Foundation from 2014 gives a very broad overview of several movement disorders *besides* Parkinson’s Disease (PD). Much of the webinar focuses on Lewy body dementia (LBD) though there is some discussion of multiple system atrophy (MSA) and a bit of discussion of progressive supranuclear palsy (PSP) — as these three diseases are often confused for each other and for Parkinson’s. And the webinar includes a terrific discussion with two physicians about research into these disorders.
What do Movement Disorders Look Like?
* Lou Gehrig’s Disease (ALS) – Gradual loss of muscle control, muscles atrophy
* Dystonia – Muscle spasms and contractions; repetitive, twisting movements
* Essential Tremor – Rhythmic shaking, most often in hands; most common movement disorder
* Lewy Body Dementia (LBD) – Cognitive impairment; hallucinations; spontaneous parkinsonism
* Multiple Sclerosis (MS) – Vision difficulties; balance problems; numbness and muscle weakness; thinking and memory problems
* Multiple System Atrophy (MSA) – Parkinson’s-like motor symptoms; more severe autonomic dysfunction
* Progressive Supranuclear Palsy (PSP) – Gait and balance problems; inability to focus eyes; cognitive impairment
Here’s a link to the recording:
Across the Spectrum: Parkinson’s and other Movement Disorders
Michael J. Fox Foundation Webinar
March 20, 2014
Brain Support Network uber-volunteer Denise Dagan recently listened to the recording and shared notes below.
March 20, 2014
LEWY BODY DEMENTIA
Alexander explained that he went 20 years before getting an accurate diagnosis of LBD. One symptom was significant fatigue, misdiagnosed as Chronic Fatigue Syndrome. Another was losing his sense of smell. 10-15 years into these strange symptoms was REM Sleep Behavior Disorder, which has since been closely linked to LBD, but at the time was not. Now, these things are considered early warning signs of PD, but at the time doctors didn’t suspect because he still doesn’t have any significant motor or gait symptoms. He was misdiagnosed with Alzheimer’s even in the presence of hallucination and perceptual symptoms. Only when he did his own research was he convinced he did not have Alzheimer’s, but LBD. He discovered a neurologist as a forerunner in the field of LBD and flew to him to confirm that diagnosis. At the time he was surprised at the ignorance of neurologists about LBD. He has since found they are most curious to learn about it.
Alexander is working on a humorous monologue called “Braking for Alligators.” He hallucinated, and braked for, an alligator in Massachusetts. He believes humor is very powerful in taking some of the weight off the experience of having such a serious diagnosis with disturbing symptoms, like hallucinations. Humor is something he can still offer others.
Dr. David Standaert is not surprised that 20 years ago doctors didn’t use the term LBD. The name was coined in the late 1980s and even in the early 90s they knew very little about it. It would have been called atypical Alzheimer’s or atypical dementia until the late 90s when they were able to find Lewy bodies in the brain and understand their significance in this neurodenegerative disorder.
Lewy bodies are an abnormal structure found in the dopaminergic neurons in Parkinson’s disease. In the late 90s, researchers discovered the protein alpha synuclein, which is a major component of Lewy bodies. That opened the door in looking across the brain. Researchers discovered that those people who had dementia and other associated symptoms Alexander described (including hallucinations) had these Lewy bodies all over the brain. These Lewy bodies are hard to see unless you stain for alpha synuclein, then they are obvious. LBD doesn’t typically have forgetfulness, like Alzheimer’s.
Dr. Susan Bressman says the abnormally mis-folded, or clumping proteins are a common phenomenon of other neurodegenerative disorders (MSA, PSP), as well.
Dr. Standaert believes that they will ultimately find that Parkinson’s Disease (PD) and LBD are the same condition (the basic disease process is the same in these two disorders) manifesting in different ways. Dr. Bressman agrees.
Alexander has participated in research at the Mayo Clinic. The DAT scan shows the dopamine deficit even though he doesn’t have typical movement symptoms. Dr. Bressman suggests the area of the brain affected determines what symptoms manifest so Alexander has RBD, loss of smell, hallucinations (pre-motor features). Alexander does take some Neupro, which, at a higher dose, worsened his hallucinations. He still takes a low dose.
MULTIPLE SYSTEM ATROPHY
Dr. Bressman says MSA can be clinically difficult to distinguish from PD. One form has a cerebellar effect with more unsteadiness and uncoordination symptoms. There is also a Parkinson’s form with really does mimic Parkinson’s. What helps distinguish it from PD are problems with autonomic issues like bladder and blood pressure control very early in the progression of the disease. It can take years to feel confident which diagnosis is correct. There is a lot of overlap in the pathology, but in MSA, instead of the neurons, alpha synuclein pathology is in the glia supporting cell. The glia cells in the brain have inclusions. Treatment overlaps as well.
Dr. Standaert agrees with Dr. Bressman. There’s no test to distinguish between MSA and PD during life. People are working on one. As a neurologist follows a patient over years symptoms become more distinct, like when motor symptoms do not respond well to PD medications, and when there are a lot of early autonomic symptoms. In MSA there are very few cognitive problems. Under a microscope, you would not mistake MSA for PD. It is still alpha synuclein, but it is in the glia in MSA rather than in the neurons in PD.
There is some loss of dopamine function in MSA because the Parkinsonian form does damage the substantial nigra, but the appearance on the DAT scan is somewhat different because in MSA you can see the damage is still somewhat even, whereas in PD the damage is asymmetric. So, the DAT scan can give you a clue, but it is not a definitive test to separate the two.
Dr. Bressman says there are papers suggesting an MRI can help to distinguish between the two, but there is a lot of debate about that. Doctors will sometimes send patients for a glucose PET scan to use the glucose metabolic pattern to distinguish between typical Parkinson’s and more of an atypical parkinsonism of some sort. The definitive diagnostic method is really to follow patients over time and watch the manifestation of symptoms, responsiveness to medications, and putting all the pieces together.
QUESTION AND ANSWER
Dave Iverson asked the doctors what can be learned about one of these neurodegenerative disorders as we learn about another of them. Dr. Standaert says they are all age-associated diseases. While young people do, occasionally, develop neurodegenerative diseases they develop after age 50, 60, 70 and beyond so age is a trigger. They are all also associated with the development of abnormal proteins. Each disorder is a different protein (misfolding protein), but at the core there are important commonalities.
Dave Iverson asked if there is an important reason to pursue the right diagnosis. Dr. Bressman says patients really want to know what it is. Knowledge is power, and getting the right diagnosis can affect getting the right treatment. When you get to MSA, PSP, CBD at this point the treatment are empiric for the most part. It is important in terms of prognosis, family counseling, clinical trials, and ultimately for targeted treatments, when those become available. We think of PD as being a homogenous entity, but there are subtypes, early onset, those with more or less gait disorder. So, on the one hand we lump them together, and on the other hand we want to customize treatment to each individual’s greatest difficulties.
Dave Iverson asks if essential tremor can progress to PD. Dr. Standaert says sometimes doctors will diagnose essential tremor (often symmetrical, runs in families, and is bilateral, so not PD) and the patient will return with real PD symptoms. People with essential tremor tend to be diagnosed with PD more frequently with PD than the general population. They thought this was due to misdiagnosis as essential tremor when it is incipient PD. DAT scan can help with this teasing out between these two conditions. Dr. Bressman totally agrees. This lingering question of whether essential tremor increases risk of developing PD, or is essential so common some percentage will go on to develop PD in the same numbers of the general population, or are some number of those diagnosed with PD misdiagnosed until the PD symptoms become obvious. That’s why we have the DAT scan. That’s what it is FDA approved for, to distinguish between these conditions. Dr. Standaert says if there is a mechanistic or genetic connection between essential tremor and PD, they haven’t discovered it, yet.
Dave Iverson asked if it is unusual for someone to have PD and then ALS, for example. Dr. Bressman says it is an unlikely but now that we have different genetic subtypes, looking at ALS through a genetics lens, it is a heterogeneous disorder and some people who have motor-neuron disorder can have parkinsonism or a PSP-like picture. So, the motor neuron picture is getting more complicated as we’re understanding the genetics. She has had patients with motor-neuron disease and parkinsonism who have turned out to have one of these genetic subtypes. It’s rare. They are separate disorders but in some subtypes you can have the two together.
Dave Iverson asked if the LRRK2 mutation that causes the most common genetic form of PD can also lead to other movement disorders. Dr. Standaert says in families where the original LRRK2 gene was discovered as a cause of PD (2-4% of cases in the US) some individuals had MSA or PSP (tau) -looking pathology. So there were other forms of neurodegenerative disease in those families. This indicates LRRK2 can not only trigger PD, but other forms of neurodegenerative diseases. Researchers wonder about LRRK2 — does something happen far upstream, modulating the response of the brain to these mis-folded proteins, perhaps modulating the inflammatory response that follows them. So, is it a general kind of gene that can enable a number of different pathologies?
Dr. Bressman has been looking for gene carriers that have these other neurodegenerative disorders or other phenotypes, but hasn’t found that so far. Family members who are gene carriers are either normal (healthy) or have PD, although it is classic PD. There is more of a gait/balance issue than a tremor. Some have a classic rest tremor. They haven’t identified motor-neuron disease or PSP or other neurologic pictures in these families. Only 28-35% of people who have this gene will develop PD before age 80. This seems to lead to a connection between a link between the gene and some upstream event, or some sort of exposure to lead to PD.
Dr. Standaert says most disease process are a combination between genetics and environment. We just don’t understand this enough in PD.
Dave Iverson asked Alexander if he has autonomic symptoms (bladder, constipation, blood pressure, etc.). Alexander says yes, he didn’t realize that they were associated to his illness until the doctor confirming LBD started asking him about some autonomic issues, specifically. Then he knew all his symptoms were related.
Dave Iverson asked Dr. Bressman if these autonomic symptoms cut across all these disorders? She says certainly PD and MSA and can be the most debilitating feature (like low blood pressure, and bladder issues).
Alexander comments (and the doctors both agree) that proper diagnosis is important, especially for those with LBD, because word needs to get out to doctors, patients and families to prevent patients being given neuroleptics (such as Haldol) which are powerful blockers of the dopamine receptors in the brain. These types of drugs are used widely in medicine when someone has hallucinations (common in LBD). If you give this to someone with LBD, even though they may not have symptoms that manifest as parkinsonian/movement related, they can become rigid and stiff for weeks.
Dave Iverson asked what is the difference in prognosis between these different disorders. Alexander says his doctor says, in his experience, the rate at which the initial condition unfolds is similar to the rate at which it further progresses. If symptoms come on gradually, it is likely to continue to progress just as slowly and is unlikely to make sharp downturns. That is good news for him as his took so long to diagnose.
Dr. Standaert agrees, although no two cases are exactly the same. The pace of one’s disease progression doesn’t change a lot over time. These neurodegenerative disorders progress at different rates from each other, ALS tends to progress much more rapidly than others.
Dr. Bressman agrees. There is no crystal ball because something new can happen as one ages.
Dave Iverson asked Dr. Bressman to talk about dystonia. She says dystonia is on the list separately because a not insignificant percentage of PD, particularly with early onset, can be caused by the disease itself or medication induced. How you treat it depends on what you think is the cause (peak dose, end of dose, early morning) so you may adjust the timing, Amantadine, or Entacapone. Ultimately, the best treatment will be better dopaminergic meds, DBS or a cure.
Dave Iverson asked if exercise helps in all of these disorders as it does for PD. Dr. Standaert thinks exercise is helpful in all of them, but in PSP there is a tremendous issue with balance and falling. MS is worsened by overheating, so be careful with that. Apply the right kind of exercise for safety to each disorder. Alexander says he only recently realized exercise is helpful for him.
Dave Iverson asked if there is a connection in both MS and ALS. Dr. Standaert says both have abnormal proteins, but the part of the brain attacked is different. MS is quite different as it is an immune attack upon the brain, but the commonality is the recent recognition of the inflammation response between all these disorders. Otherwise, the cause, diagnosis, and management is quite different.
Dave Iverson asks about the more drastic drop in blood pressure between in MSA than in PD. Dr. Bressman says that is true. The treatments are very similar, but too many patients don’t talk about it. If they are feeling faint they should tell their doctor and have regular blood pressure checks to discuss how to manage it. Its dangerous because it can lead to falling, but there are a lot of treatment options. Some people are even still on old blood pressure meds to lower blood pressure from cardiologists prior to adding a neurodegenerative disorder, and those aren’t needed anymore.
Dave Iverson asks Dr. Bressman if she is hopeful that connections between research will lead to treatments across all these disorders. She is quite hopeful and the research is broad and applicable to not only insight into PD, but other disorders with respect to the search for a cure or better uses of the treatments they already have.
Dave Iverson asks Dr. Standaert if he things that is encouraging for pharmaceutical companies. He says the more they learn about these diseases the more they realized there are shared commonalities of attack to research treatments. Success in one will really open the door to success in others. The rare disorders may not get the funding for research, but will benefit from those getting funding. PD may not be just one condition because there are more than one gene that can trigger it, and a multitude of symptoms. Dr. Bressman says one type of ALS may share a treatment option with some type of PD.
Dave Iverson asks Alexander to close the conversation. Alexander says he has found with respect to his hallucinations is to use them as creative prompts for writing poetry and other creative works. That is always potentially possible and there is more attention to this in the dementia care community.
A month ago, Brain Support Network and UCSF held an all-day conference on PSP and CBD. One attendee reflected on the conference this way: “Excellent speakers, all of them. This was a well-balanced program between research and practical.”
The morning was focused on updates from nine researchers, with two panels. The afternoon was focused on practical information from a neurologist, a neuro-ophthalmologist, a social worker, a physical therapist, a speech therapist, a person with a PSP diagnosis, a person with a CBD diagnosis, and a person who cared for his wife with PSP. There were also two practical panels in the afternoon.
Nine generous families sponsored the videorecording of the conference. Brain Support Network asked a medical writer to take notes throughout the conference.
See our conference webpage —
On that page, you’ll find the:
* conference agenda
* full set of notes from the day
* link to the conference video
If you’d rather pick and choose which speakers and panels you are interested in, you can use that same webpage to find:
* each speaker’s one-page handout (distributed at the conference)
* most speakers slides (not all speakers allowed their slides to be shared)
* presentation or panel notes (prepared by BSN’s medical writer)
* video of the presentations and panels
Brain Support Network makes these conference materials available to you at no charge. We thank the speakers, attendees, and sponsors. Without their generosity, this conference would not have been possible. Please support our work in hosting the conference and sharing these conference materials by making a charitable contribution today.
UPDATED (11-27-17): This was a great conference! See our complete conference webpage here:
Here’s the tentative agenda (subject to small changes):
PSP/CBD Research Update and Practical Conference
Saturday, October 28, 2017
Crowne Plaza Foster City (California)
Brain Support Network
Organized in partnership with:
University of California San Francisco Memory & Aging Center
Generously sponsored in part by Biogen.
Check-in; continental breakfast; visit exhibitor tables
Welcome by Brain Support Network
RESEARCH UPDATE – PART ONE
Adam Boxer, MD, UCSF MAC – overview of PSP clinical research
Richard Tsai, MD, UCSF MAC – tau PET imaging for CBS
Dianna Wheaton, PhD, FTD Registry – update on the registry (which includes PSP and CBD)
Larry Golbe, MD, Rutgers Robert Wood Johnson – investigating the geographical cluster of PSP in France
Daniel Lee, PhD, University of South Florida, Tampa – pre-clinical research update on tauopathies
PANEL of previous five speakers, moderated by Alex Klein, PhD, CurePSP
RESEARCH UPDATE – PART TWO
Haung (Ho) Yu, PhD, Columbia – research update on clearance of misfolded tau protein
Stewart Clark, PhD, University of Buffalo – research update on creating a pre-clinical model for PSP
Adam Gerstenecker, PhD, University of Alabama at Birmingham – research update on functional ability in PSP
Gerard Schellenberg, PhD, Penn Neurodegeneration Genomics Center – what we know and don’t know about PSP and CBD genetics
PANEL of previous four speakers, moderated by Alex Klein, PhD, CurePSP
Lunch and visit exhibitor tables
PRACTICAL CONFERENCE – PART ONE
Donna Schempp, LCSW – resilience and coping
Leslie Wolf, person with CBD – Holding Steady on Shaky Ground
Phil Myers, (former) caregiver to wife with PSP, Brain Support Network – Eight Things We Learned From This Journey
Jeanette Brown, MD (retired), person with PSP – Being (a) Patient with PSP
PANEL of previous four speakers, moderated by Robin Ketelle, RN, UCSF MAC
PRACTICAL CONFERENCE – PART TWO
Sharon Sha, MD, Stanford – Corticobasal Syndrome, Corticobasal Degeneration, and Progressive Supranuclear Palsy: What are the Tauopathies?
Megan DePuy, SLP, private practice, San Mateo – what can we do about speech and swallowing problems?
Erica Pitsch, DPT, UCSF – what can we do about movement problems?
Heather Moss, MD, neuro-ophthalmology, Stanford – what can we do about eye movement problems?
PANEL of previous four speakers, moderated by Robin Riddle
Closing remarks by Brain Support Network
Note: We are using “CBD” to refer to both CBS and CBD.