“Spouses Face Hurdles When Caring…”

This news article is about the fact that “caring for a sick or disabled elderly relative exacts a toll — physical, emotional, financial — on any family member, but being a spousal caregiver brings particular challenges.” One of the researchers mentioned in the article is co-author of a recent study of LBD caregivers. He says: “Spouses are likely to take on more than they can reasonably do.” Other key excerpts are:

“In an oft-cited study published in the Journal of the American Medical Association in 1999, University of Pittsburgh researchers followed nearly 400 elderly spousal caregivers for four years and reported that those experiencing mental or emotional strain had 63 percent higher mortality rates than non-caregivers. (Caregivers not experiencing emotional or mental strain did not have elevated mortality rates.)”

“And a study published this year by a team from the University of South Florida and the University of Alabama at Birmingham found that high caregiving strain among spouses increased the risk of strokes by 23 percent; the association was particularly strong among husbands caring for wives.”

Here’s the full article.

http://www.kaiserhealthnews.org/Stories … ivers.aspx

Spouses Face Hurdles When Caring For Themselves, Ill Loved Ones

By Paula Span
Kaiser Health News
(produced in collaboration with The Washington Post)
May 25, 2010

They met on a blind date in 1949 and married two years later. They lived in the same Cape Cod-style house in Silver Spring for nearly 50 years. So when Leonard Crierie was diagnosed with Alzheimer’s disease in 2005, there was no question that his wife, Betty, would take care of him at home for as long as she could.

Betty led him into the shower, helped him dress each morning and took him everywhere with her because, once he started wandering, as some dementia patients do, she dared not leave him alone. She learned how to change the colostomy bag he wore since he’d survived rectal cancer years earlier. She slept, fitfully, with a monitor by her bed so that she could respond if he needed her at night.

“It was difficult, but I was able to take care of him,” says Betty, now 80. “Because it happens slowly, you don’t realize how bad it’s getting.”

She agreed to have Leonard attend an adult day program at nearby Holy Cross Hospital — he enjoyed socializing there — so that she could get a few hours’ break several times a week; she found a Holy Cross caregivers support group very useful. But she refused the pleas from her three adult children to hire an aide to help at home. “I always felt like I had it under control,” she explains, though her children thought the $18-an-hour cost also troubled a frugal woman who shops at dollar stores.

As the months passed, “we could see the stress level affecting her,” recalls her daughter Linda Fenlon. “The frustrating part was, we wanted her to have some independence, some quality of life. But she saw it as her duty in life to take care of him.”

For four years, Betty Crierie rarely asked for or accepted her family’s help, until a Wednesday last June. As she left her support group meeting, she remembers, “I got this funny feeling in my chest.” It worsened on the 10-minute drive home. She called her daughter and said, “I’m calling 911. I think I’m having a heart attack.”

‘In Sickness And In Health’

Caring for a sick or disabled elderly relative exacts a toll — physical, emotional, financial — on any family member, but being a spousal caregiver brings particular challenges.

“Spouses are older and dealing with their own age-related health limitations,” says Steven H. Zarit, a Pennsylvania State University gerontologist. The tasks they shoulder have grown more demanding: Family caregivers now administer arsenals of medications and undertake procedures, from wound care to dialysis, that were once the province of medical professionals.

Moreover, today’s longer life spans, in which once-fatal conditions such as heart disease have become manageable chronic illnesses, mean that the “sickness” part of “in sickness and in health” can last for many years. Spouses determined to single-handedly honor their vows, says Suzanne Mintz of the National Family Caregivers Association, “are using their old rules to fight a new problem.”

The medical and psychological literature have long reported that caregivers face risks to their own well-being, especially when they’re caring for people with dementia. Caregivers under stress have higher levels of depression and anxiety; their immune systems suffer. A 2005 Commonwealth Fund overview found that caregivers of all ages reported chronic conditions — including heart disease, diabetes, cancer and arthritis — at nearly twice the rate of non-caregivers, 45 percent vs. 24 percent.

In an oft-cited study published in the Journal of the American Medical Association in 1999, University of Pittsburgh researchers followed nearly 400 elderly spousal caregivers for four years and reported that those experiencing mental or emotional strain had 63 percent higher mortality rates than non-caregivers. (Caregivers not experiencing emotional or mental strain did not have elevated mortality rates.)

And a study published this year by a team from the University of South Florida and the University of Alabama at Birmingham found that high caregiving strain among spouses increased the risk of strokes by 23 percent; the association was particularly strong among husbands caring for wives.

“Spouses are likely to take on more than they can reasonably do,” Zarit says.

Betty Crierie was the classic example: Caring for her increasingly disabled husband, trying to shelter their adult children from the burden, unwilling to bring in a costly home-care aide when she felt she was doing fine on her own — until she had her heart attack. “We didn’t realize how much she was doing until we took turns taking care of Dad ourselves,” Linda Fenlon says. “It was so labor-intensive. We very quickly realized she couldn’t continue.”

While their mother recovered, the children moved their father into a nursing home, a wrenching act for all concerned. Betty visited Leonard there two or three times a week, continuing to do his laundry at home, until he died five months later at age 83.

Depression-Era Values

Why is it so difficult for older caregiving spouses to seek help? Zarit’s research has shown that compared with adult children taking care of an ailing parent, spouses don’t turn to adult day programs until later in the course of illness, and they’re more apt to withdraw the participant after a short time.

Sister Kathy Weber, who leads the Holy Cross support group that Betty Crierie attended, sees a Depression-era-bred reluctance to spend money on care, even when couples can afford it. “They’re supposed to get along somehow and squirrel it away for their kids – who want them to use it now, for their care, which would make the children’s lives easier, too,” Weber says.

Spouses don’t want to lose control of their homes or their relationships. Sometimes they hope to protect their partners’ dignity, not wanting children to see how diminished they’ve become. “There’s a lot of pride there,” Weber says.

What might help, caregiver advocates say, is for health providers to regard older couples as a unit, recognizing that a caregiver’s compromised health could prematurely institutionalize an ailing spouse. Some geriatric practices already do so. “On the intake forms in doctors’ offices, there should be questions to identify whether someone is a family caregiver,” suggests Mintz. “That would alert the physician and the staff to the situation and raise questions about that person’s own health. Is she taking care of herself?”

Meanwhile, President Barack Obama’s proposed 2011 budget would add $102.5 million for family caregiving programs, “a step in the right direction,” Mintz says. The money would boost existing programs that serve family caregivers, including training and counseling, referrals, respite care, transportation, adult day programs and home care. AARP analysts estimate the increased funding could help an additional 200,000 families. Family caregivers can use the help: Medicare pays for doctors and hospitals but provides only very limited post-hospitalization home care, and Medicaid (which covers only the poor) allots most of its dollars to nursing homes. The financial burden of caring for a spouse at home falls mostly to families themselves.

But even with better support, watching a partner decline is difficult. “They are about to lose their lives as they’ve known them,” Weber explains.

That’s what happened to Sheila Fridovich, whose husband, Bernard, developed Pick’s disease, a form of dementia, in his late 60s. Sheila kept him at home in Annapolis, eventually hiring a daytime aide, for nearly six years.

“I couldn’t eat; I couldn’t breathe; I didn’t have a moment’s peace,” she acknowledges. Yet she refused to see a therapist or join a support group. “I needed to iron it out in my own head,” she says.

“We grew up in a generation where getting help from a therapist is not stigmatized,” theorizes her daughter Lauri Fridovich Lee, who joined a support group online. “For the older generation, it is.”

Eventually, consulting with a Veterans Affairs physician about drug coverage, Sheila discovered that Bernard, a Navy veteran, was eligible for admission to a specialized dementia unit at the VA Community Living and Rehabilitation Center in Baltimore. She moved Bernard there in 2006. At 79, he’s still a resident and gets excellent care, she says. But after a stroke, he cannot speak, and she’s not sure, on her Sunday visits, if he knows who she is.

“It’s a traumatic experience for a husband and wife, far more than for their kids,” Fridovich says now. She’s only 71, still working part time as an educational consultant, but “the way I live is not the way I lived before. I’m married but I’m not; I have a husband but I don’t. I’m in no man’s land.”

Paula Span is the author of “When the Time Comes: Families With Aging Parents Share Their Struggles and Solutions.”

Related Resources
For information, support and referrals for spouses and other family caregivers, contact:

The National Family Caregivers Association

National Alliance for Caregiving
[email protected]

Family Caregiver Alliance


Strength for Caring

Here’s a 3-minute video that is related to this article:
http://www.kaiserhealthnews.org/Multime … ivers.aspx

PSP, CBD, and MSA Conference – Extensive Notes (Nov 2009, Australia)

This post provides the notes Brain Support Network volunteer Robin Riddle took from the recordings on this conference:

“The Challenge of Movement Disorders: Exploring diagnosis, management and best practice interventions in relation to PSP, MSA, and CBD”

Topic: “Coping with Diagnosis: An Intro and Overview of the conditions (CBD, MSA and PSP), including diagnosis, current treatment options and recommendations”

Attendees: allied health professionals (MDs, RNs, PTs, OTs, STs, social workers, etc)

Date: November 25, 2009

Organizer: Parkinson’s Victoria (parkinsonsvic.org.au) and PSP Australia (psp-australia.org.au)

Speaker: Dr. David Williams, The Alfred and Cabrini Hospital, Melbourne


The notes are provided by part or segment as follows:

Part 1 (8 minutes) – On all atypical parkinsonism disorders (PSP, MSA, CBD)

Part 2 (10 minutes) – On PSP (mostly on Richardson’s syndrome with an intro to PSP-P and PAGF at the end)

Part 3 (10 minutes) – On PSP (specifically on PSP-Parkinsonism and pure akinesia with gait freezing)

Part 4 – (10 minutes) – On PSP

Part 5 (9 minutes) – On PSP (first half) and MSA (second half)

Part 6 (8 minutes) – On MSA (first third) and CBD

Part 7 (5 minutes) – On CBD (first half) and all atypical parkinsonism disorders (PSP, MSA, CBD)


Part 1 (8 minutes) – On all atypical parkinsonism disorders (PSP, MSA, CBD)

If it’s not Parkinson’s disease (PD), what is it? Many disorders can look a little like PD including: PSP, MSA, CBD, vascular parkinsonism (caused by strokes), Huntington’s disease (inherited), Wilson’s disease, Neuronal intranuclear inclusion disease, neurofilament inclusion body disease, spinocerebellar ataxia 6 (3, 7; rare). Today, we are talking about the first three. You might see patients described as having “parkinsonism” as we aren’t sure which of these disorders it is. Only Wilson’s disease has curative treatments.

Diagnosis is important for patients: disease label and identity. I prefer to err on the side of riskiness and make an early diagnosis. Having a diagnosis helps for planning. Diagnosis is important for research and quality assurance.

PD is 25 times more common than any other bradykinetic rigid syndrome. (I see 20 patients with PD and only one or two with PSP or MSA.) Medication can improve many of the symptoms. Survival is usually 15 to 25 years after onset. Symptoms: loss of sense of smell; REM behavior disorder (during sleep; act out dreams); visual hallucinations (usually developed later in the disease); good or excellent response to levodopa. These four symptoms don’t happen in the other three conditions we are talking about today — PSP, MSA, and CBD.


Part 2 (10 minutes) – On PSP

Here are the notes I took from this segment, which focuses on the classic form of PSP, called Richardson’s syndrome though, near the end, there’s an intro to other PSP forms, including PSP-Parkinsonism and pure akinesia with gait freezing:

Richardson, Steele, and Olszewski described PSP in late 50s and early 60s. John Steele is still alive and lives on Guam. Dr. Steele argues that the disease should really be known as Richardson’s disease or Richardson’s syndrome.

It’s really wrong to say that patients with PSP look like those with Parkinson’s because they really don’t get much in the way of bradykinesia (slowed movement) until five or more years after onset.

Mild dementia is often developed in PSP. It may happen early on.

Restriction of full lateral gaze. The eyes often become completely fixed.

Rather than the hunched posture of PD, PSP patients are often upright, with the neck usually extended backwards.

The postural reflexes are much more impaired.

The necks are stiff. The eyes tend to close over.

How do we identify patients with PSP? Diagnostic criteria are: gradually progressive disorder; onset later than 40 years; postural instability and falls in first year of disease AND vertical (up or down) supranuclear palsy. By definition, someone 39 or younger doesn’t have PSP.

Supranuclear = coming from the brain rather than the brain stem.

Supportive criteria of PSP: symmetric akinesia or rigidity (often in the neck; usually less in the arms than in PD); abnormal neck posture (severe axial dystonia in the neck, which is typical); frontalis overactivity (patients often look surprised or startled); poor or absent response to levodopa; early dysphagia (swallowing problems) or dysarthria (speech disturbance); early onset of cognitive impairment (executive dysfunction; decreased verbal fluency; not frank dementia; not loss of memory); normal sense of smell; no visual hallucinations; no REM behavior disorder. The last three are in contrast to PD patients.

Clinical features of PSP: 65 years is mean age of onset; 7 years is mean disease duration with Richardson’s syndrome (so 50% die before 7 years and 50% of people die after 7 years); most common modes of death are respiratory dysfunction or as a result of a fall (causing a brain hemorrhage, for example).

PSP is caused by abnormal protein accumulation, predominantly in the basal ganglia, which is where movement comes from. Spontaneous movement is slow. Static movement like neck posture is exaggerated. And eye movements are reduced.

Not everyone with PSP has these diagnostic features. This is what my PhD was about. What if a patient comes into the clinic with normal eye movements and a bit of tremor? Unfortunately most people don’t go by the textbook and there is a range of different presentations of PSP pathology. Most don’t respond well to medications, and there is usually the same mode of death at the end. But in some cases we can say to the patient that “you’ve got the good form of PSP; you are going to live 12 to 14 years” if they ask that question.

What if there is no supranuclear gaze palsy (SNGP)? Usually SNGP develops within the first two years. But in about 30% of patients, it doesn’t. They might have a different type of PSP. Other clinical syndromes specific for PSP-tau pathology including: PSP-Parkinsonism (patient looks like they have Parkinson’s for the first two to eight years and then develop more classic signs of Richardson’s syndrome), pure akinesia with gait freezing; corticobasal syndrome.


Part 3 (10 minutes) – On PSP

[This segment focuses on two less common forms of PSP — PSP-Parkinsonism and pure akinesia with gait freezing.]

I’m emphasizing the importance of research. Prior to our publishing this paper in 2005 [Williams et al, Brain 2005], the only way to diagnose PSP in the clinic was adhering to the diagnostic criteria I showed you before. But 32% of cases studied for our 2005 paper (with pathologically-confirmed PSP) lacked classic Richardson’s syndrome features. These people were told they had “atypical parkinsonism” because they didn’t fit under the PSP banner. This subgroup is called PSP-Parkinsonism: asymmetric onset of symptoms (just one side or one arm or one leg); tremor; moderately good response to levodopa. So, they have no early falls, no eye movement abnormality, and no early cognitive dysfunction in contrast to those with Richardson’s syndrome. They look much more like they have Parkinson’s disease for the first few years.

Video of woman with PSP-Parkinsonism. She had unilateral rest tremor that was treated with levodopa. Her posture is more upright than what you’d expect with PD. Very subtle eye movement changes several years into the disease. She’s 13 years into the disease.

Video of man with PSP-Parkinsonism. He lived 11 years. Never developed eye movement abnormalities. Rest tremor in leg. Small handwriting. Unusual stride pattern. He had only PSP upon brain analysis. The people looking after him thought he had PD for the whole duration. We don’t know if he had visual hallucinations, loss of sense of smell, or REM behavior disorder but the lack of these symptoms might have alerted his clinicians to something other than a PD diagnosis. He had no sign of Parkinson’s pathology upon brain tissue analysis.

PSP-P can be differentiated from PD by: normal sense of smell; no visual hallucinations; no REM behavior disorder; normal cardiac autonomic function (as seen through a cardiac MIBG).

What about the other condition of pure akinesia with gait freezing? I was always told in medical school that this was always due to vascular parkinsonism, so parkinsonism caused by small strokes in the frontal lobe or the basal ganglia. But most of the patients that have this type of clinical picture have PSP-tau pathology.

The diagnostic criteria we put together for pure akinesia with gait freezing are: marked by gradual onset, which implies neurodegeneration (in contrast to sudden onset, which would imply stroke) and early freezing of gait or speech (in the first one or two years). Absent are: sustained response to levodopa; tremor; rigidity in arms and legs (sometimes there’s a little in the neck); imaging changes suggestive of vascular disease or Binswanger’s. Absent in first five years are: limb rigidity; dementia; opthalmoplegia; vascular disease.

Video of man with PAGF. Good arm swing. His only problem in gait freezing. Blepharospasm. Has developed some slowing of vertical eye movements, ten to twelve years into the disease. Rapid but small amplitude movements; this is a lot different than what we see in PD. He has rapid hypophonia: speaks quickly but softly. (In PD, patients speak softly and slowly.) These are clues that it’s PSP-tau pathology, rather than PD. The biggest clue is probably that they don’t get better at all with medication. And, gait freezing, if it happens early in PD, always gets better with medication.

Video of man with PAGF. Costs $1500/day to see a specialist at Mayo Clinic. This patient was told the same thing by Mayo that the specialists in London had told him. For about the first eight years, his only problem was occasional gait freezing. This leads to falls at home. He’s been given the visual cue (paper on the ground), and he steps over it.

What’s the difference in these conditions? Very importantly, we can talk about prognosis. This is important for a lot of patients. Some patients don’t want to hear anything about what’s going on but others do want to know and plan things out.

Prognosis rate varies by disease subtype: Richardson’s syndrome, PSP-P. This is important for therapeutic interventions and counseling as well. If you are older at onset, your survival is a bit less. You can’t pick on any one person and say exactly what their survival is going to be but you can imagine that the accumulation of disabilities is going to increase at a faster rate if you are older.


Part 4 – (10 minutes) – On PSP

[This segment focuses on pure akinesia with gait freezing (first third) and is then about PSP overall.]

How do we separate PAGF from PD and from VP (vascular parkinsonism)?

PAGF: rapid hypophonia (talk fast but softly; fast micrographia (write in small letters but quickly)

PD: rigidity; tremor; response to levodopa; visual hallucinations

VP: leg rigidity; tremor; early cognitive dysfunction; pyramidal signs; history of stroke on scans

PAGF is differentiated from PD by: normal sense of smell; no visual hallucinations; no REM behavior disorder; normal cardiac autonomic function (cardiac MIBG)

Microtubule associated protein tau is ubiquitous in the adult brain. Its normal function is assembly and stabilization of microtubules (neuronal cell structural elements). Normally tau protein binds to microtubules in axons.

In tauopathies, like PAGF, tau is redistributed to the cell body and accumulates to form insoluble, fibrillary deposits, or tau protein clumps. We don’t know if tau causes the disease or if it’s the result of the disease. We do know it characterizes the disease. It happens in PSP, not in PD.

There is a genetic basis. This doesn’t mean it’s inherited. About 70% of us have a certain type of genetics for this tau protein. The 30% who don’t are less likely to get PSP. This is a genetic modifier, not a risk factor or a cause.

If on brain autopsy a patient’s brain has mainly the basal ganglia being involved with the tau pathology, that patient is more like to have had PSP-Parkinsonism or pure akinesia with gait freezing. Compared to if a lot of the cortex is involved, these patients will only have Richardson’s Syndrome. So knowing what brain regions are involved and what symptoms this causes should give us insight into whether a patient has PSP-Parkinsonism or Richardson’s Syndrome. My view is that there are other genetic modifiers that make the outlook better for those with PSP-Parkinsonism and worse for those with Richardson’s Syndrome. We will find this out over the coming years.

Are there any diagnostic tests for PSP? No.

Cardiac MIBG looks at nerves around the heart. The MSA patient has a normal scan. In PD, the heart doesn’t take up the tracer due to loss of nerves around the heart. It doesn’t usually cause heart problems. Patients with PSP would be expected to have a normal scan. This type of scan would be somewhat useful in differentiating between PSP and PD but they aren’t accurate in everyone.

Smell Sense (UPSIT) includes 40 items for a scratch and sniff test. Patients with PD score in the 10th percentile for smell discrimination. PSPers score in the 18th percentile — well into the normal range. As a group we can separate the two conditions quite well but on an individual level there may be great variability. So it’s not good at separating the two conditions.

What about other biomarkers? There’s a lumbar puncture test that’s being shown in Italy to separate out PSP. Tau fragments in CSF are a biomarker. Problem is that the pathology is very similar between PSP and CBD so those patients should be similar. That’s a criticism of the technology in the paper. But what it means is that it’s very difficult to develop in vivo (during life) tests that discriminate between PSP and Parkinson’s and other conditions.

What are the treatment options for PSP?

* levodopa: if parkinsonism present, I always try this. I always try levodopa if patients have rigidity and bradykinesia; usually there’s not a response. Sometimes when you stop the medication, people feel worse so you’ll see a lot of people with PSP on a small dose of Parkinson’s medications just because they felt a bit worse off it it but you can’t really tell much difference.

* amantadine: developed in the 1950s by the US Army to reduce the risk of flu. It was found to improve PD symptoms a little bit in the 1960s. Occasionally we’ll find that gait freezing in PSP can improve a little bit if we use this medication but the result usually is unfortunately disappointing.

* amitritypline: tricyclic antidepressant. Probably the most prescribed medication in all of neurology (used for pain, migraines, depression, hyper-salivation, urinary problems). One in five patients with PSP find that they have louder speech and improvement in swallowing. It’s certainly worth trying if those are issues.

* botulinum toxin: used for blepharospasm (tendency for eyes to close over; injection around the eyes) and in the neck (if the extension rigidity is very uncomfortable; axial dystonia).

* zolpidem CR: helpful in the odd patient. There are a few case reports of someone getting out of their chair when they are on the right dose of zolpidem. I’ve never had that experience but I’ve seen the videos so I do believe it happens. Might be helpful for gait freezing.

* DBS: not a worthwhile option in PSP. This has been shown several times.

PSP Australia, in conjunction with Parkinson’s Australia, has developed a 100-page carer’s manual with important info about the management of PSP, prognosis, welfare issues, and end of life decisions. It provides expert advice.

There are a few emerging drug trials for PSP. We are starting to try to adjust some things about how that tau protein accumulates in the cells and is associated with nerve cell death.

Lithium is one of the oldest and one of the simplest drugs around. It’s been used in bipolar disorder and depression for 50 years. It’s a GSK inhibitor that reduces phosphorylation of tau. Lithium stops the enzyme that makes the tau bunch together. CurePSP-sponsored study in the UK and US is now going on: lithium vs. placebo. 30 planned in each group. Lumbar puncture is mandated, which is probably why the recruitment for this study has been slow. And they’ve had lithium toxicity problems. No results expected for several years. I don’t believe lithium is the answer. I’ve had one patient on lithium for 15 years and still developed PSP. And another patient who was started on lithium because of the rumor of this study emerging a couple of years ago, and he died due to lithium toxicity during the heatwave in London. [Robin’s note: This Australian conference was before the NIH-funded lithium study was ended due to tolerability issues.]


Part 5 (9 minutes) – On PSP (first half) and MSA (second half)

Co-enzyme Q10 is supposed to change the progression of the disease, not improve symptoms. Quite expensive so a lot of people try to get it on the internet from North America. In a study published in the Movement Disorders journal in 2008, there was a miraculous recovery of patients with PSP patients who took CoQ10 (500mg of CoQ10 for six weeks). So miraculous that it’s unbelievable. We should look carefully at these studies. The patients taking the placebo were on average seven years older than those taking CoQ10. I’d also argue that a two-point improvement on a 100-point scale has no clinical significance. If you repeat the test a further six months down the line, you’d find the improvement goes the other way. A bit naughty publishing there. If I was reviewing it, I would’ve rejected it.

NP-12 is another GSK3-inhibitor. It doesn’t have the toxicity of lithium, another GSK inhibitor. It is a molecule originating from a rational design program with inhibitory activity of GSK-3. (The molecule was specifically designed for this task.) There is a multicenter, placebo-controlled trial in PSP, with up to 300 patients. It has started in Europe. It will probably go for three or four years. It’s called the “Noscira trial.” Noscira is a Spanish company. Tools used to measure outcomes: Golbe rating scale and PSP QoL scale.

Allon – davunetide intranasal is a neuroprotective agent. This is an NIH/CurePSP-sponsored trial. This is an exciting trial. Preclinical experiments indicate that davunetide has neuroprotective (look after brain cells so they aren’t dying), neurotropic and cognitive protective properties. Supposedly stabilizes sick and dying nerve cells. Vasoactive intestinal peptide-like properties. Phase II clinical trial (safety and efficacy). Placebo-controlled trial. Patients will have to have lumbar puncture, MRI, and clinical assessments (PSP Rating Scale) five times over a 12-month period. Australian site – Melbourne. Looking to start April 2010. The medication is delivered via nasal spray, which is always good for patients who can’t swallow very well.

Unfortunately many of the neuroprotective studies looking particularly at stroke models haven’t been very useful. There is a fair degree of skepticism about a neuroprotective study. But it hasn’t been tried in a tauopathy, particularly one that progresses like PSP.


(Starts at 4:07) Multiple system atrophy is about as common as PSP. It looks completely different under the microscope in post-mortem examination, where there isn’t any tau accumulation but rather other proteins.

How do we make an MSA diagnosis and how do we differentiate it from PD? Well, these guys surely have parkinsonism (slow movements, muscle stiffness, they often have a little bit of tremor as well). But the defining feature is that other systems are involved as well. And the autonomic system is absolutely a part of that diagnostic paradigm. If there’s no autonomic dysfunction, then you can’t diagnose MSA.

It’s not “multi system atrophy,” and it’s not “multiple systems atrophy.”

MSA = autonomic dysfunction + parkinsonism + cerebellar dysfunction. There’s MSA-Parkinsonism and MSA-Cerebellar.

Yes, there are autonomic symptoms in PD but, in MSA, autonomic failure almost always precedes parkinsonism. Autonomic failure includes: (measurable) postural hypotension (simply because they don’t have the autonomic response to lower blood pressure that gravity gives us when we stand); impotence (reported by men; early signs are some ED rather than complete impotence; sexual dysfunction in women, though this is hard to get at); constipation (bowel changes over the last three or four years, which have been getting worse); urinary difficulties (ubiquitous; I consider these essential for diagnosis of MSA; hard to determine in multiparous women and in men with prostate problems but usually we look for a pattern of urinary problems that has emerged over the last couple of years; includes urinary urgency, frequency, and nocturia).

Between 25% and 50% of MSA patients have cerebellar dysfunction as well. The cerebellum is involved with coordination and balance. Sometimes cerebellar dysfunction can be the primary problem. In MSA-C, there is often little parkinsonism. Idiopathic late onset cerebellar dysfunction with autonomic failure.

In MSA, tremor is quite rare.

In MSA, response to medication is variable. It’s disappointing compared to PD. But I must say that I usually find that I’m using dopaminergic medication to improve muscle stiffness and slowness of movement. (The slide says: “the response with dyskinesias can be excellent.”)

Diagnostic criteria of MSA:

* Autonomic: BP drops > 20/10 after 3 minutes of standing; urinary urgency, nocturia, or frequency; erectile dysfunction in men; abnormal sweating

* Parkinsonism: often symmetrical at onset (in PD, it’s usually one side)

* Cerebellar: eye movements are normal

* Pyramidal: extensor plantar responses

Mean age of onset in MSA is 55 years — about 10 years earlier than PSP. Mean disease duration is 7 years. But this is a skewed view of things. In maybe a third of people, it’s rapidly progressive such that death occurs in 2 or 3 years. On the other side of that 50% percentile, equally, there are plenty of people who make it out past 15 years and out towards 20 years with MSA. An idea about prognosis (3 years vs. 15 years) can usually be guessed at during the first consultation after you’ve reviewed the progression. Most common modes of death in patients who die after 2 or 3 years are: respiratory dysfunction; sudden death due to muscle spasm around the neck (nocturnal apnea/asphyxia/central); falls.


Part 6 (8 minutes) – On MSA (first third) and CBD

Video of man with MSA. Dysmetria. Nystagmus. Extrapyramidal rigidity. Not much in the way of bradykinesia; a little bit on the left side. He noticed symptoms on the left side. The voice has become soft.

MSA can be differentiated from PD to some extent by: normal sense of smell (sense of smell usually better than in PD, though there can be abnormalities); no visual hallucinations; can have REM behavior disorder; normal cardiac autonomic function (cardiac MIBG isn’t so reliable, particularly if you are younger than 60 years of age).

Prognosis in MSA: patients with severe autonomic dysfunction at the outset have worse survival; rapid fall-off and then a long survival; the older you are, the faster the disease progresses. Comparing survival in those over 65 and under the age of 55.

Massive MSA research effort in Europe going on now. It’s still in the phase of understanding what the research is telling us. Hopefully we’ll start getting involved in the clinical trials once they start internationalizing them.


(starts at 3:09) Corticobasal degeneration is a pathological diagnosis, and none of us is a pathologist. Which means that none of us can make this diagnosis. During life, we call this “corticobasal syndrome.” Diagnostic accuracy is less than 50%. There is no validated diagnostic criteria for CBD. We should talk about “corticobasal syndrome” as a constellation of clinical features. I encourage you to use that terminology. We are demanding this in the research literature as well.

The pathology is caused by the tau protein. It causes:

* Asymmetric parkinsonism: dystonia (abnormal muscle tone, usually down one side; often in just one limb); cortical sensory loss (demonstrated by drawing the number in someone’s affected hand); myoclonus (brief, shock-like jerks); alien limb (arm feels like it’s not part of the body and it doesn’t it’s own thing; German in the wheelchair in “Dr. Strangelove” exhibits alien limb phenomenon)

* Frontotemporal dementia is often present. It may be a speech disturbance (eg, progressive non-fluent aphasia) or a behavioral disturbance (eg, frontal behavior syndrome).

If you see someone with the syndrome, you can’t say that they definitely have the pathology. What else can cause corticobasal syndrome? CBS can be caused by: CBD, PSP, TDP-43 frontotemporal dementia (FTD-U), vascular disease, Alzheimer’s disease.

If you say someone has “CBS caused by CBD pathology,” it’s just as likely as you’ll be wrong.

I don’t have any videos of people with pathologically-confirmed CBD.

Video of man with CBS (can’t guess at underlying pathology): stiff, useless right arm that is held in a dystonic posture. If it had been a stroke, you’d expect right facial problems and right limb problems. He has partial alien limb. Has a few myoclonic jerks. Can’t conceptualize because of basal ganglia and cortical pathology. Asymmetry. Often the other side will get involved 5 or 6 years down the trail.

Video of woman with CBS. Again, this could be confused as a stroke but the history isn’t that of a stroke. Useless hand. Subsequently developed blepharospasm and eye movement abnormalities. So you will agree with me that she probably has underlying PSP-tau pathology as the cause of this syndrome.

CBD = pathology. CBS = clinical syndrome.


Part 7 (5 minutes) – On CBD (first half) and all atypical parkinsonism disorders (PSP, MSA, CBD)

CBD patients often have ideomotor and limb kinetic apraxia, which is uncommon in PSP, PD, and DLB.

Myoclonus is a good feature to separate them except it’s only present in about 50% of the patients.

Eye movements can be abnormal. Usually there are some subtle differences which we try and pick up clinically. The slide says: “poor correlation in the literature with pathology.”

To try an illustrate the difficulties of diagnosing this condition… This is a paper we’ve just submitted of 1440 brains that came to the Queens Square Brain Bank over a 20 year period. 21 cases clinically diagnosed with CBD (using the old terminology). Of those 21 cases, 16 cases did NOT have CBD. This is a useless diagnostic paradigm! Of the 21 cases, 5 had pathologically confirmed CBD. Of the 1440 brains, 19 cases were pathologically diagnosed with CBD. Of the 19 cases, 5 cases had the clinical diagnosis of CBD (and were diagnosed during life) and 14 cases had other clinical diagnoses.

Of the patients that actually had that tau pathology of CBD, the diagnoses were:

* Initial clinical diagnosis: 8 PD, 2 PSP, 2 spastic paraparesis, 1 akinetic rigid syndrome, 1 AD, 1 CBD, 1 depression, 1 FTD, 1 MSA, 1 Tourette’s dynrome.

* Final clinical diagnosis: 8 PSP, 5 CBD, 2 PD, 1 FTD, 1 PNFA, 1 focal cortical atrophy with myoclonus; 1 Tourette’s syndrome

I’m not sure I could’ve gotten the diagnosis right either!

(At 2:31) If it’s not PD, what is it? Prognosis is worse; burden of care is worse; medications less likely to help; injuries more likely to occur.

Retrospective study from a couple of years ago looking at the time from symptom onset to falls. Patients with PD tend not to fall in the first 10 years. Patients with PSP tend to fall in the first 2 years. In MSA, they tend to fall in the first 3 or 4 years. In vascular parkinsonism, in the first 6 or 7 years. In dementia with Lewy bodies, in the first 4 or 5 years. Just from simply looking at falls, and the ramifications of that, the burden of care is more severe in the non-PD conditions.

What can we do about it? The PSP Information Kit is vitally important for every patient, family, and nurse to have. [Robin’s note: this kit is available online at psp-australia.org.au]

It’s the role of all of us to provide: education; optimize home and community environment; maximize function (this may be through inpatient or outpatient rehab; this may be through medication trials; this may be through equipment optimization at home); carer support (carers have a big impact on quality of life and disease duration); encourage research.

One very rich man in Canada lived with what he thought was PD for 30 years. Turned out it was PSP. This family pumped in heaps of money for a fulltime physiotherapist and a couple of fulltime carers. Even a couple of years before he died, he was still being walked with 2 physiotherapists. Now he had an atypical form of PSP but this story goes to show that if you are maximizing the support for the carers and the physiotherapy, you are really going to get the best out of the patient and improve the quality of life.

Conference on PSP, CBD, and MSA (Australian conference, Nov 2009)

This is one of the best resources I’ve seen in a long time!  It’s terrific for PSP, very good for MSA, and good for CBD.  I offer a big thank-you to Bob Dunn, a member of the CBD-related Yahoo!Group.  He emailed me a link to these videos over the weekend.  I spent all Sunday watching them and taking notes.

Speakers at a November 2009 conference for allied health professionals (RNs, PTs, OTs, STs, social workers, etc) in Melbourne, Australia were recorded, and the videos were posted to YouTube.  The conference has a long title:  “The Challenge of Movement Disorders: Exploring diagnosis, management and best practice interventions in relation to PSP, MSA, and CBD.”  It was organized by Parkinson’s Victoria (parkinsonsvic.org.au) and PSP Australia (psp-australia.org.au).

One of the world’s top researchers of PSP and MSA, Dr. David Williams, who is based in Melbourne, is a presenter for over an hour.  He’s the co-author of a very important article on PSP and MSA, titled “Clinical outcomes.”  And he’s the primary author of all the major papers coming out about the various types of PSP.  Every PSP researcher I know of has adopted Dr. Williams‘s use of the terms “Richardson’s syndrome” and “PSP-parkinsonism.”

The multi-hour conference is broken into 10-minute segments.  For a link to all (but one) of the segments, see:

The video includes each speaker’s slides, though in some cases they are hard to see.  (I noted that one of the segments is missing from that link.  It’s not a very important segment.)

My best guess as to the conference agenda is:
* Dr. David Williams, Neurologist – diagnosis and treatment of PSP, MSA, and CBD
* Dr. Fiona Fisher, Clinical Neuropsychologist – cognitive changes in PSP, MSA, and CBD
* Dr. James Howe, Consultant Neurologist – advanced care planning and end of life decisions
* Victor McConvey, Parkinson’s Specialist RN – management of PSP, MSA, and CBD in a collaborative fashion
* Jen Daddow, Carers Victoria – support for caregivers

Since the audience is healthcare professionals, a fair amount of medical terminology is used.  Those of you who have been reading medical journal articles, listening to the CurePSP webinars when they’ve had neurologists as guest speakers, or reading my emails for awhile will have no problem understanding all of the presentations.  Note that very little of the info presented is Australia-specific.  Some Australian terminology is used; for example, the word “carers” is used rather than “caregivers.”

I’m going to send out separate emails with links to each of the 10-minute segments and the notes I took, by speaker.  I’ve indicated which of the three disorders each segment pertains to, or whether it’s a general presentation on all three disorders.  The third speaker on advanced care planning didn’t have too much that was disorder-specific so I may send this out to our full support group (including the Lewy Body Dementia folks).



Family history of parkinsonism or dementia in PSP and CBS

This Italian group has been publishing lots of papers lately on genetic investigations in PSP and CBD. I don’t believe they are participating in the PSP/CBD Genetics Project.

This study of 129 PSP patients and 101 CBS patients evaluates the prevalence of family history (among first degree relatives) for dementia or parkinsonism. “Positive FH [family history] was found in 31.8% of PSP and in 31.7% of CBS. Familial aggregation was lower in the age-matched control group” (21.8%).

“Patients with PSP had higher positive FH for Parkinsonism (63.4%) when compared to FH for dementia (36.6%). In CBS, FH was equally distributed between Parkinsonism (53.1%) and dementia (46.9%).”

The authors conclude: “These results argue for familial aggregation in PSP and CBS, further underlying the importance of genetic background in these disorders.”

These are similar results to a Dutch study published in 2009, where the authors “reported that the 33% of the patients with PSP had at least one-first-degree relative with dementia or Parkinsonism compared to 25% of the control subjects.”

I’ve copied the abstract below.


European Journal of Neurology. 2010 May 11. [Epub ahead of print]

Familial aggregation in Progressive Supranuclear Palsy and Corticobasal Syndrome.

Borroni B, Goldwurm S, Cerini C, Cosseddu M, Meucci N, Mariani C, Pezzoli G, Padovani A.
From Centre for Neurodegenerative Disorders, Neurology Unit, University of Brescia, Brescia, Italy.

Background: Studies on familial aggregation might be of help to evaluate whether the genetic background has a key role in Progressive Supranuclar Palsy (PSP) and Corticobasal Syndrome (CBS). Only a few studies are available.

Objective: To evaluate the prevalence of positive family history (FH) in PSP and CBS in a large sample of patients.

Methods: Two hundred and thirty patients and 110 controls entered the study. Patients underwent an extensive clinical, neurological and neuropsychological assessment as well as a structural brain imaging study. A clinical follow-up further confirmed the diagnosis. Familial aggregation was carefully recorded by a standardised questionnaire.

Results: One hundred and twenty-nine PSP (age at onset = 66.6 +/- 7.3, female = 46.1%) and 101 CBS (age at onset = 62.8 +/- 8.9, female = 41.6%) were consecutively enrolled.

Positive FH was found in 31.8% of PSP (n = 41) and in 31.7% of CBS (n = 32). Familial aggregation was lower in the age-matched control group compared to patient group (21.8%, P = 0.05).

Patients with PSP had higher positive FH for Parkinsonism (63.4%) when compared to FH for dementia (36.6%). In CBS, FH was equally distributed between Parkinsonism (53.1%) and dementia (46.9%).

In addition, FH was not associated with age at disease onset in PSP (FH+ versus FH-, 67.0 +/- 7.3 vs. 66.7 +/- 7.1, P = 0.788) and in CBS (62.6 +/- 7.9 vs. 62.9 +/- 9.5, P= 0.877).

Conclusions: These results argue for familial aggregation in PSP and CBS, further underlying the importance of genetic background in these disorders. Further studies on possible genetic modulators or genetic epistasis contributing to PSP and CBS development are warranted.

PubMed ID#: 20482608 (see pubmed.gov for this abstract only)

Disease-modifying therapies in PSP

This research team in Marburg, Germany is one of the best in the PSP community. This article reviews “therapeutic approaches aiming at disease-modification rather than mere symptomatic neurotransmitter-replacement therapy.” The two approaches reviewed are agents that target mitochrondrial dysfunction and agents that target tau dysfunction.

This article describes the current state of PSP clinical studies, called “exciting therapeutic developments” by the authors, in the quest for “urgently needed disease-modifying therapies.” The studies are summarized in Table 1 below. I’ve added some notes with a few details I know about these studies.

The abstract and Table 1 are copied below.

A scanned copy of the full article has been posted to the CurePSP website. I’m not sure that’s legal so before anyone figures it out, I suggest you save a copy to your hard-drive if you are interested in the full article. See:

http://psp.org/includes/downloads/stame … eview2.pdf


Here’s the abstract:

Brain. 2010 May 14. [Epub ahead of print]

Rational therapeutic approaches to progressive supranuclear palsy.

Stamelou M, de Silva R, Arias-Carrión O, Boura E, Höllerhage M, Oertel WH, Müller U, Höglinger GU.
Department of Neurology, Philipps University, Marburg, Germany.

Progressive supranuclear palsy is a sporadic and progressive neurodegenerative disease, most often presenting as a symmetric, akinetic-rigid syndrome with postural instability, vertical supranuclear gaze palsy and frontal lobe deficits. It belongs to the family of tauopathies and involves both cortical and subcortical structures.

Although the exact pathophysiology is not yet fully understood, several lines of evidence point to a crucial contribution from both genetic predisposition and mitochondrial dysfunction.

Recently gained insights into the pathophysiology of this disease have led to several hypothesis-driven therapeutic approaches aiming at disease-modification rather than mere symptomatic neurotransmitter-replacement therapy.

Agents targeting mitochondrial dysfunction have already shown a positive effect in a phase II study and further studies to verify and expand these results are ongoing. Clinical studies with agents targeting tau dysfunction such as tau-kinase inhibitors, tau-aggregation inhibitors and microtubule stabilizers are in preparation or ongoing.

This review presents the current pathophysiological concepts driving these exciting therapeutic developments.

PubMed ID#: 20472654 (see pubmed.gov for this abstract only)

This is Table 1, reformatted so it works on the PSP Forum:

Table 1 – Clinical trials aiming at disease modification in PSP

Substance: Coenzyme Q10
Target: Mitochondrial dysfunction
Mechanism: Complex I cofactor
Phase II trial: Significant improvement (Stamelou et al, 2008)
Phase III trial: Recruiting (NCT00382824 on clinicaltrials.gov)
[Robin’s note: This is the study that’s been underway for several years at Lahey Clinic in Boston. It’s now been expanded to include Beth Israel Deaconess Medical Center in Boston and the University of Alabama Birmingham. The last word I had from the study administrator, Stephanie Scala, the dosage for CoQ10 is 2400mg/day.]

Substance: Puruvate, creatine, niacinamide
Target: Mitochondrial dysfunction
Mechanism: Multifunctional cocktail
Phase I trial: Active (NCT00605930 on clinicaltrials.gov)
[Robin’s note: clinical trials spells the first substance as pyruvate]

Substance: Lithium
Target: Tau dysfunction
Mechanism: GSK-3beta inhibitors
Phase I trial: Stopped because of poor tolerability (NCT00703677 on clinicaltrials.gov)
[Robin’s note: Thanks to a local support group member and others on this Forum who participated in this trial.]

Substance: Valproic acid
Target: Tau dysfunction
Mechanism: Aggregation inhibitors
Phase II trial: Active (NCT00385710 on clinicaltrials.gov)

Substance: Nypta
Target: Tau dysfunction
Mechanism: Microtubule stabilizers
Phase II trial: Recruiting (NCT01049399 on clinicaltrials.gov)
[Robin’s note: This trial is now recruiting at at a couple of US institutions, including PMDI in SoCal.]

Substance: Methylthioninium chloride
Target: Tau dysfunction
Mechanism: Microtubule stabilizers
Phase II trial: Significant improvement in Alzheimer’s disease (Wischik et al, 2008); PSP not studied
[Robin’s note: I assume this is Rember.]

Substance: Danuvetide
Target: Tau dysfunction
Mechanism: Microtubule stabilizers
Phase II trial: PSP study in preparation
[Robin’s note: Danuvetide is also called NAP or AL-108. A 12-person pilot study is underway now at UCSF.]

Speech and Swallowing Q&A – 5/13/10 Webinar Notes

Today’s CurePSP (psp.org) webinar was presented by Laura Purcell Verdun, a speech-language pathologist who is experienced at treating those with movement disorders.  The topics were speech and swallowing problems.  The presentation was designed around some questions she had received in advance.  It was a terrific webinar.

Though today’s webinar was promoted as being about PSP, CBD, and MSA, very little of the info was disorder-specific.  So those coping with any atypical parkinsonism disorder will find value in this post.

There are three sources of info on the webinar:

1- The presenter’s slides have been posted to the CurePSP website:


2- The webinar was recorded, and the recording has been posted to the CurePSP website:


3- My notes below.  (I’ve added topic headings and grouped the questions/answers by topic.)


Speech and Swallowing Q&A for PSP, CBD, and MSA
Date:  May 13, 2010
Host:  CurePSP
Presenter:  Laura Purcell Verdun, speech/language pathologist, [email protected]

PSP, CBD, and MSA are rare aggressive neurodegenerative diseases that will impact swallowing and communication abilities at some point in the disease progression.  Management of swallowing and speech disorders in these circumstances requires changing intervention strategies as the disease progresses.


Is choking a bad thing?
* Yes
* Sign that the timing, coordination or strength of the swallow mechanism may be changing
* Sign that material (food, liquids, saliva) may be “going down the wrong way”
* Not comfortable and potentially scary
* Receive instructions on the Heimlich Maneuver

Why does someone choke only when eating soup?
* Broth is considered a thin liquid, which move faster than any other consistency.  If the swallowing mechanism is moving slowly, airway protection may be delayed.
* Soups, particularly, broth-based, are multiple-consistency items.  It’s hard for the swallow mechanism to manage the thin liquids, and the solids that need to be chewed, at the same time.
* Options:  use cream-based soups (denser consistency so they move slower) or blend soups so they are one consistency


What is a swallowing study?
One type is called VFSS (videofluoroscopic swallowing study)
* this type may also be called MBSS (modified barium swallowing study)
* video xray of eating and drinking
* presented with various consistencies and volumes of food/liquids/pills
* defines present level of swallowing function compared to normal
* guides therapy efforts
Another type is called FEES (feberoptic endoscopic swallowing study)
* swallowing is examined via a flexible nasoendoscope

Do I need to have a swallowing study?
* Not necessarily
* For the swallowing study to be most revealing, it should reflect the home eating environment.  Specific foods, self-feeding, straws, etc.  Bring in 1-2 food/liquid items that have proven to be most problematic.
* Too often the swallowing study illustrates “you’re swallowing fine” because the swallowing study is a very controlled environment
* This study defines the extent of the swallowing problem and what is to be done about it


What is aspiration?
* Aspiration is when saliva, food, or liquids travel below the vocal folds into the airway (trachea)
* All these items should travel through the throat (pharynx) directly to the food tube (esophagus) to the stomach
* Chronic aspiration may cause aspiration pneumonia, an infection in the lungs

How do I know if I am aspirating?  Will the impact on my lungs be immediate?  Will I feel discomfort before pneumonia sets in?
* May not know you are aspirating.  “Silent aspiration” is when food, liquids, or saliva go down the “wrong way” without any outward sign.
* Only way to confirmation aspiration is by testing.  Tests include chest xray, swallowing study, etc.
* Effects may or may not be immediate but may be cumulative
* Monitor for chronic low grade fever, increased chest congestion, and coughing (especially coughing that occurs more during mealtimes than at other times of the day)
* Discomfort most likely to arise from coughing

Is it possible to have aspiration for liquids without dysarthria?
* Yes
* Dysarthria = when there is difficulty pronouncing sounds, consistent articulation errors, often with muscle weakness and discoordination
* In these neurodegenerative disorders, these two symptoms (dysarthria and dysphagia) often develop alongside each other
* Once dysarthria is present, there is also concern for changes in swallowing because many of the same muscles and nerves are involved

Who is at risk for aspiration pneumonia?  (From Langmore, et al.  Dysphagia 1998.)
* Altered mental status
* Advanced age
* Presence of a feeding tube
* Prior history of aspiration pneumonia
* Malnutrition
* Physical immobility
* Feeding dependence
* Poor oral hygiene


Do thickeners taste OK?
* Yes
* They change the consistency of the liquid or food item, not the flavor
* Commercial thickeners come in two types — powder and gel.  Powder = Thick-It, Thick-It 2, Thicken Up, NutraThik, Thicken Right, etc.  Gel = Hydra-Aid, SimplyThick (good choice if you are dealing with diabetes because it’s not starch-based).
* Pre-thickened liquids from Aqua Thick, Thick&Easy Drinks, etc,

Sources for commercially-available thickeners:  [Robin’s note:  start with these websites and then enter the name of the product in the search box]
Thick-It:  thickitretail.com
ThickenUp (from Resource):  nestle-nutrition.com
Hydra-Aid:  linksmed.com
SimplyThick:  simplythick.com
Thick & Easy:  hormelhealthlabs.com
Aqua Thick:  cwimedical.com
A good online medical supply store (for thickeners and other items):  brucemedical.com

Are there other ways to thicken without commercial thickeners?
* Yes:  oatmeal, gelatin, fruit purees, blend in frozen fruits, bananas, banana flakes (available at health food stores), potato flakes, Silken tofu (soft)
* Blend vegetable soups to thicken them
* I don’t recommend eating JellO in the presence of swallowing problems.  In my experience, JellO is very problematic to swallow.

More thoughts about thickened liquids:
* May not be tolerated well by lungs if aspirated
* May contribute to reduction in fluid intake such that you can become dehydrated
* Not entirely clear how well water is absorbed in the gut from thickened liquids
* Quality of life considerations


What does someone hold foods/liquids in her mouth for 15-20 seconds before swallowing?
* Could be related to changes in the neurophysiology of the swallow mechanism, or cognition, including apraxia or impaired sensation.
* Suggested approach to dealing with this situation:
– stick with food/liquid items where this seems to be less of an issue
– verbal cues may help (“go ahead and swallow”) but don’t rush someone
– manually apply pressure under base of tongue moving forward may trigger swallow
* Meal times should be limited to anywhere from 30-60 minutes.  Consider smaller, more frequent meals.
* Concern is for expending more calories trying to eat than consuming


What meals are appropriate for a swallowing disorder?
* Maintain a balanced diet
* Don’t necessarily eliminate foods but prepare foods differently to enhance ease and safety of swallowing
* Stick with moist and tender foods, such as dark meat chicken, fish, casseroles, pastas, stews, cooked vegetables, canned fruit, etc.
* Use condiments, gravies, or sauces to lubricate foods
* Avoid highly textured, particulate (something that breaks into pieces), and dry foods, such as red meats, rice, corn, firm breads, crackers, nuts, popcorn, etc.
* Meats cooked medium rare may be more tender than something well done
* Blend multiple consistency items such as fruit cocktail, broth-based soups, oranges, watermelon, cold cereal.  (Example:  If you are eating a bowl of Cheerios, let the Cheerios sit to soak up milk, then pour off the remaining milk, and eat the soggy Cheerios.)
* Foods may need to be pureed in advanced stages of swallowing difficulties
* Try foods/liquids of different temperatures
* Try carbonated liquids, sparkling vs. still water
* Consider more frequent, smaller meals
* Consider use of nutritional supplements (Ensure, Boost, Carnation Instant Breakfast, Scandishake, etc)

Swallowing cookbooks:
The Dysphagia Cookbook, 2003
Meals for Easy Swallowing, 2005.  See:  als-mda.org/publications/meals
Easy-to-Swallow Easy-to-Chew Cookbook, 2002
Soft Foods for Easier Eating Cookbook:  Recipes for People who have Chewing and Swallowing Difficulties, 2007.
I Can’t Chew Cookbook: Delicious Soft Diet Recipes for People with Chewing, Swallowing, and Dry-Mouth Disorders, 2003.

Swallowing and feeding products:
* Flexi-Cut Cup and Provale Cup:  from alimed.com
* Independence Spillproof Flo Tumbler:  from kcup.com
* Wedge Cup:  from wedgecup.net
* Maroon Spoons:  from proedinc.com
* Scooper Plate with Non-Skid Base:  from bindependent.com
* Skidtrol Non-Skid Bowl:  from maddak.com
* A variety of products from Bruce Medical Supply:  brucemedical.com

Swallowing tips that families or other speech therapists have offered:
* Place a digital picture frame with audio on the dining table.  Play recorded messages for mealtimes that say “eat slow, one bite at a time, small sips” etc.
* Add bananas to thicken smoothies
* Use Fla-vor-ice tubes.  Empty the contents, fill with water or OJ, and position upright and freeze

Will using a straw help with swallowing?
* I can go both ways on this.  Using a straw can be problematic because it can accelerate the liquid to the back of the mouth/throat.  Another issue is that you are sucking in at the same time, your airway is still open.  But a straw may be beneficial because you can limit intake.  Sip – hold for a second in the mouth (letting the throat catch up) – then swallow.  Some people do better by using a straw rather than drinking from a cup.  Some people get a rhythm going using a straw and taking multiple swallows.
* This can be evaluated during a swallow study

How can we plan ahead for swallowing problems in the future?
* No talking and eating/drinking at the same time
* Monitor for mouth stuffing and chugalugging liquids
* Take time to eat

If a family member with PSP is gaining weight, is it OK to exceed 30 minutes for mealtimes?
* I’ve seen weight gain in PSP, not in CBD or MSA.  In PSP, there’s a tendency towards disinhibition, including rapid drinking and rapid eating.
* This isn’t a concern from a swallowing point of view.  It may be an issue for ambulation — both the patient getting around and the caregiver helping the patient.
* Goal should be to keep weight stable


I started taking nortriptyline, an antidepressant.  It seems to have helped my swallowing.  Could this be the case?
* Would suspect that improvement is not related to the medication
* This medication may dry up secretions somewhat
* Discuss with your neurologist

What is Vital-Stim?  Will it help persons with these diseases?
* Reports to apply small electrical current to stimulate the muscles responsible for swallowing
* Must be prescribed by an MD
* Limited data, no studies specific to neurodegenerative diseases except for one very limited study with MS.  Clinical efficacy and utility of this therapy remains inconclusive.
* I don’t recommend VitalStim for these populations


When might a feeding tube be indicated?
* Recurrent aspiration pneumonia
* Reduced enjoyment of mealtimes
* Increased duration of mealtimes such that you are burning more calories than you are getting in
* Progressive weight loss or dehydration, despite optimizing feeding situation
* Trouble swallowing coexisting with depressed alertness
* Evidence of significant silent aspiration with swallowing study or other clinical evidence of frequent aspiration

What do I need to consider about a feeding tube:
* Discussions need to take place sooner rather than later, and repeated frequently.  Prefer to initiate discussions prior to a health crisis.  Patient and family should agree in advance with the doctor about what is hoped to be accomplished from trying a feeding tube.  Decisions must revolve around assessment of burdens and benefits.  Requires value judgments and consideration of quality of life.
* Gastric contents and saliva can still be aspirated
* Feeding tube placement does not preclude oral intake
* No randomized controlled research trials to indicate whether tube feeding is beneficial compared to continuation of oral feeding for survival


How important is oral hygiene?
* Very important
* Goal is to keep mucosa of the mouth clean and moist to minimize bacteria of the mouth.
* If the mouth is moist, it’s easier to swallow
* May be increased incidence of aspiration pneumonia in those with poor oral hygiene in the setting of swallowing difficulties

What should I do for oral hygiene?
* Scrupulous dental care (visit dentist, changing to a better toothbrush)
* Avoid smoking, alcohol (including mouthwashes that contain alcohol), and caffeine.  Alcohol and caffeine may dry the mucosa of the mouth.
* Drink plenty of water throughout the day
* Minimize non-cooked dairy products as these may thicken secretions
* Rinse out mouth after meals
* Club soda or sparkling water may help cut through secretions
* Avoid gels and mouthwashes that contain alcohol, menthol, or whitening products
* Nighttime humidifier at bedside as these keep the mouth, nose, and throat mucosa moist.  Keep them clean.
* Consider a suction machine, in later stages.  One drawback is that the more you use the machine, the more the nose and throat get dried out, thereby causing the body to produce more secretions.  A suction machine may be helpful to clear the mouth before meals.
* Make sure dentures are clean and well-fitting
* Consult with a dentist

Oral care products:
* Biotene:  toothpaste, mouthwash, and Oral Balance Moisturizing Liquid; products contain three primary enzymes that boost and replenish salivary defenses; available at Target, WalMart, etc.; biotene.com; 800/922-5856
* Oasis moisturing mouthwash
* Plak-Vac Suction Toothbrush:  800/325-9044; trademarkmedical.com/personal/personal-oral.html
* Toothette Swabs:  dental hygienists say that they aren’t good for cleaning out the mouth because they aren’t abrasive enough

How effective are WaterPiks?
* Helpful in getting out large particles.
* I don’t know if they are abrasive enough to clean enamel and plaques.  I view this as a supplement to brushing.
* Also, if someone has swallowing problems, I don’t know if they can tolerate a WaterPik.


Is speech and swallowing therapy efficacious?
* Depends on circumstances and what is trying to be accomplished
* Efficacy of exercise is difficult to document given variable rates of progression
* Some studies describe longitudinal progression of speech and swallowing dysfunction.  (Goetz, et al, Neurology 2003.  Muller, et al, Archives of Neurology 2001.)
* Very few studies regarding treatment of speech and swallowing in these populations.  (Article by Countryman, et al, Journal of Medical Speech Pathology 1994.)

What is LSVT (Lee Silverman Voice Treatment)?
* Proven to significantly improve voice quality in PD.  Relevant to our discussion tonight given the similar symptomatology.
* Very specific, intensive treatment program emphasizing LOUD speech.  A loud voice generates improved respiratory support, articulation, and facial expression/animation.
* Developed by Lorraine Ramig, PhD
* lsvtglobal.org

Should I keep doing LSVT forever?
* Specific to these populations, yes…whether it is LSVT or some other form of speech therapy
* Exercises should be maintained daily
* These are progressive disorders.  Communication will deteriorate over time.
* Speech therapy is of limited benefit if those skills learned are not maintained outside the clinic

Will LSVT help my swallowing?
* One report (Sharkawi, et al, JNNP 2002) showed some improved swallowing movements in patients with PD.  The disorders we are talking about tonight exhibit some similar deficits.
* LSVT hasn’t been studied in these populations

A family member completed speech therapy almost a year ago.  Now his speech has declined.  Is it possible to improve a second time?
* This is a common scenario.  This raises the issue of whether direct speech therapy should be considered in the first place, and what techniques specifically should be addressed.
* It’s best to intervene early.  Late-stage interventions are often frustrating.
* Emphasis should be placed on functional communication
* Improvement could be possible.  The issue is:  can it be maintained?  That’s likely to be more difficult as the communication impairment has progressed over time.

I have MSA and I’ve taken speech therapy yet my speech is bad and gets worse.  Is practice over time very helpful?
* Exercise does not appear to be contraindicated in these three disorders
* Whether practice helps depends on:  severity of speech impairment and effect on overall speech intelligibility, state of underlying disease process, specific exercises you are doing
* A trial of speech therapy (a couple of visits) to investigate stimulability is often reasonable.  Can you carry over what you’ve learned?
* Emphasis should be placed on improved speech in the home environment.  You may need to consider assistive communication.

When is speech therapy covered by Medicare or other insurance?  I was told that with PSP, speech therapy wouldn’t improve my speech, so the expenses wouldn’t be covered.
* 2010 Medicare cap is $1860 for combined speech and physical therapy, and a separate $1860 for occupational therapy
* asha.org has two good resources on insurance coverage:
* Depends on what the goals are for speech therapy.  Are you focusing on speech restoration or speech compensation (trying to make adjustments and optimize the abilities you presently have)?  Are you looking at direct speech therapy or assistive communication?

Is the $1860 cap for one-year or a lifetime?
* It’s an annual cap
* It often times gets adjusted from year to year


I can only speak in a 2-word whisper.  What exercises should I do?
* Need to determine why the voice is so weak.  Get an exam by an ENT and a speech pathologist.
* Options:  if speech remains relatively intact, try LSVT.  And consider a personal voice amplifier.  (Example – Chattervox from chattervox.com)

Will breathing exercises help to strengthen my weak voice?
* Taking a breath prior to speech is almost always beneficial.  (“Take a breath and tell me what you want for dinner”)
* Inspiratory and expiratory muscle training can improve respiratory muscle strength and endurance.  But will this change voice and speech production?  Not so, for one MS study.

Is there a procedure to help the voice work better?
* Weakness of voice is common.  This is attributed to vocal fold atrophy and weakness of respiratory drive to keep vocal folds vibrating and project the voice.  (With atrophy, the muscles of the vocal folds are thinner and weaker.)
* Vocal fold augmentation is a procedure where a filler is injected into the vocal folds to bulk them up.  Makes it easier to vocal folds to vibrate against one another.  Variable benefit in these populations.  There are no studies.  Two things that indicate if you would more likely benefit:  if you have strong breathing muscles and if the problem is with voice rather than speech.  See adiesse-voice.com for info on the most common filler.


EMST (expiratory muscle strength training)
* Was found to be helpful to increase cough and swallowing in PD
* Dr. Sapienza (Univ of FL) is presently doing a study with PD and MS.  [Robin’s note:  In 2009, Dr. Sapienza was also studying EMST in PSP.  I will follow up with her because she was going to send me the preliminary data.]
* Device called Aspirate EMST 150.  Available as aspireproducts.org.  Simple to use and maintain.  There is a specific routine that is recommended.
* I don’t know if this would be of benefit but it has the potential to help


Is there anything else I can do to improve my speech so others will be able to understand me?
* Is it a problem with the voice, meaning the sound source, or the speech, meaning how you pronounce words?
* Make sure to have listener’s attention
* Provide context upfront.  Example:  “I want to talk about what’s for dinner.”
* Optimize environment.  Turn down radio, turn down TV, put your newspaper down.
* Communication is a two-way street
* Make sure hearing impairments are addressed
* Speak slowly
* Exaggerate speech and mouth movements
* Do not trail off — pronounce all sounds.  Voice must be strong from beginning to end.
* Space between words
* Be more forceful with speech
* Use a minimum, yes-no system


What do I need to consider with assistive communication?
* Is this serving as the primary means of communication or to supplement speech?
* With whom will you need to communicate?
* What type of info needs to be communicated?
* How will you access the device?  (physical capabilities, visual capabilities)
* Any cognitive limitations?
* What type of environment?
* Consider safety within the home or outside the home.  Medic-alert system.

What assistive communication options are available?
* Two system types:  unaided (rely on the person to convey the message through gestures, sign language, etc) and aided systems (relies on the use of equipment or tools)
* Aided systems range from low-tech (paper, dry erase board, communication board) to high-tech (speech generating devices or written output; electronic or software-based devices using pictures, words or phrases to create messages)

How will someone communicate when he can no longer talk?
* Speak with your speech pathologist to investigate these resources
* Alphabet supplementation with an “alphabet board.”  Speaker points to the first letter of each word spoken.  Or, can spell the entire message.
* Communication board.  One example is a WordPower OnBoard, which is a manual communication board composed of the 100 most common English words.  There’s an alphabet board on one side.  The other side can be customized.  Available from:  store.mayer-johnson.com/us/word-power-onboard.html
* Written-choice communication.  Requires partner support.  Partner establishes the context or question, and written choices.  Partner writes down “milk – coffee – Coke” and asks “What would you like to drink?”
* iPhone, iPad, and iPod application called Proloquo2Go.  Preset communication buttons.  Text to speech.  Save customized sayings.  iPhone and iPod are harder to use because they are smaller.  proloquo2go.com. Might be $190.
* Lightwriter (toby-churchill.com) or Dynavox (dynavoxtech.com):  portable text to speech communication aids.

Will insurance cover a speech generating device (SGD)?
* Yes, Medicare provides benefits for all currently available digitized speech output devices
* There are two good resources on insurance coverage:
* Consult with your speech pathologist to determine if this will be helpful and which one to get

AAC online resources:


Have you had any experience using an electrolarynx to improve speech?
* This is a battery-operated device used primarily in those who have lost their voice/larynx to cancer.  The hand-held vibrating head provides a sound source.
* Listen to a sample of this computer-sounded voice at:  webwhispers.org/library/BobAL.mp3
* Requires hand coordination for neck placement and on-off, as well as relatively intact speech
* Not typically indicated
* I have ever used this device in this population


How do I find a speech pathologist?
* Find someone who is ASHA certified (asha.org/findpro) and state-licensed
* LSVT:  lsvtglobal.com
* Movement Disorders Society:  movementdisorders.org
* APDA:  apdaparkinson.org  [Robin’s note:  the Information & Referral Center in your local area may have a list of speech pathologists who work with those with Parkinson’s Disease.]
* NPF:  parkinson.org  [Robin’s note:  click on “Find Local Resources” at the top.]
* Ask your neurologist for a referral to a speech language pathologist.  Ideally, look for an SLP with experience in movement disorders or any neurodegenerative population.


Concluding remarks:
* Consult with your MD and speech pathologist to tailor a program specific to your needs
* Continue to follow-up with them


These flyers will be available in the near future through CurePSP:
* designed for speech language pathologists (“what every SLP should know…”), OTs, and PTs
* on PSP, CBD, and MSA
* you can get them for your SLP, PT, and OT
* available through Trish Caruana, MSW, [email protected]

Analysis of speech in PSP vs. PD (German research)

Dr. Larry Golbe, a PSP expert, said in early 2007 that the spastic and ataxic speech of those with PSP is distinctive and occurs “in almost no other condition.” I have known of people who were diagnosed with PSP by their speech/language pathologist. Locally, one of our support group members was told by an SLP that his wife had certainly not had a stroke because her speech was dissimilar to what happens with a stroke.

This German research, just published, looks at 14 patients with a clinical diagnosis of the Richardson’s syndrome type of PSP (RS), 12 patients with a clinical diagnosis of the parkinsonism type of PSP (PSP-P), and 30 patients with a clinical diagnosis of Parkinson’s Disease.

“Speech examination was based on the acoustical analysis of a standardized four-sentence reading task. Several speech variables were measured to assess phonation, intonation variability, speech velocity, and articulatory precision. … Global speech intelligibility was evaluated…”

The researchers found: “In the PSP group, speech velocity, intonation variability, and the fraction of intraword pauses as a measure of articulatory precision were significantly reduced… Only in the male PSP patients, vowel articulation was found to be impaired. Global speech performance was worse in the PSP group in comparison with the PD group… No differences of speech variables were seen between RS and PSP-P patients.”

The last part was surprising to me because one of the primary symptoms of RS is dysarthria while it is not a primary symptom of PSP-P. Perhaps it’s a matter of timing as to when dysarthria occurs in RS and PSP-P but when it does occur the characteristics are the same.

In conclusion, the authors state: “PSP patients feature a mixed type of dysarthria with hypokinetic and spastic components that differ significantly from the speech performance of PD speakers.”


Journal of Voice. 2010 May 8. [Epub ahead of print]

Acoustical Analysis of Speech in Progressive Supranuclear Palsy.

Skodda S, Visser W, Schlegel U.
Department of Neurology, Knappschaftskrankenhaus, Ruhr-University of Bochum, Bochum, Germany.

BACKGROUND: Dysarthria often is an early and prominent clinical feature of progressive supranuclear palsy (PSP). Based on perceptual analyses, speech impairment in PSP reportedly consists of prominent hypokinetic and spastic components with occasional ataxic features.

OBJECTIVE: To measure objectively and quantitatively different speech parameters in PSP as compared with Parkinson’s disease (PD) by acoustical analysis and to correlate these parameters with disease duration, global motor, and speech impairment and with the subtype of disease (Richardson’s syndrome [RS] vs parkinsonian type of PSP [PSP-P]).

PATIENTS AND METHODS: Twenty-six patients with clinical diagnosis of PSP (n=14 classified as RS and n=12 classified as PSP-P) and 30 age- and gender-matched patients with clinical diagnosis of PD were tested. Speech examination was based on the acoustical analysis of a standardized four-sentence reading task. Several speech variables were measured to assess phonation, intonation variability, speech velocity, and articulatory precision. All participants were tested according to Unified Parkinson’s Disease Rating Scale/Motor Score (UPDRS-III) and staged according to Hoehn and Yahr stages. Global speech intelligibility was evaluated on the basis of the UPDRS-III speech item.

RESULTS: In the PSP group, speech velocity, intonation variability, and the fraction of intraword pauses as a measure of articulatory precision were significantly reduced, whereas the percentage of speech pauses was prolonged as compared with the PD group. Only in the male PSP patients, vowel articulation was found to be impaired. Global speech performance was worse in the PSP group in comparison with the PD group and showed a correlation to some distinct speech dimensions. No differences of speech variables were seen between RS and PSP-P patients.

CONCLUSIONS: PSP patients feature a mixed type of dysarthria with hypokinetic and spastic components that differ significantly from the speech performance of PD speakers. This probably reflects the widespread neuropathological changes in PSP comprising basal ganglia as well as pontine and further brainstem regions.

Copyright © 2010 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

PubMed ID#: 20457507 (see pubmed.gov for this abstract only)

“If spouse has dementia, your risk rises too”

This news story will be of most interest to those married to someone with dementia. An excerpt (from the very end of the article):

An expert unaffiliated with the new study called the finding “compelling,” but not necessarily surprising. “Caregiving is very stressful,” said Dr. Gary W. Small, director of the University of California-Los Angeles, Center on Aging… “Studies have shown that caregivers for dementia patients have a high risk for major clinical depression. And there has been a study that showed that people who are prone to stress are at higher risk for Alzheimer’s.”


If spouse has dementia, your risk rises, too
Stress of caregiving may be to blame for 6-fold increase, researchers say

By Linda Carroll
msnbc.com contributor
updated 5:19 a.m. PT, Thurs., May 6, 2010

Being married to someone with dementia may sharply increase your own risk of developing the condition, a new study shows.

Utah researchers found that seniors had six times the risk of developing dementia if they lived with a spouse who had been diagnosed with the condition, according to the study, which was published in the Journal of the American Geriatrics Society. And the increased risk was substantially higher for husbands than for wives.

“The good news is that most of the spouses did not develop dementia,” said the study’s lead author, Maria Norton, an associate professor in the department of Family, Consumer and Human Development at Utah State University, in Logan. “But this does alert us to the increased risk for some of them. We need to be taking care of the caregiver and finding ways to maximize the positives of care giving.”

The study followed 1,221 couples for 12 years. All 2,442 study volunteers were at least 65 years old and free of dementia at the outset. By the end of the study, 255 of the seniors had developed dementias, two-thirds of which were Alzheimer’s disease.

Though the study did not explicitly ask whether spouses had taken on the role of caregiver, Norton says it’s safe to assume they did.

She and her colleagues were so surprised by their findings that they ran their numbers again, this time accounting for the spouses’ ages, genders and whether they had a form of the APOE gene that raises the risk for Alzheimer’s disease. In their new analysis, they also factored in socio-economic status, which can be a surrogate for shared environmental risk factors, such as access to medical care, diet and exercise.

The number barely budged: having a spouse with dementia still resulted in a six-fold increased risk of developing the condition. And the news was far worse for men: increase was almost 12-fold, as compared to a four-fold increase in women.

Norton and her colleagues don’t yet know what is at the root of the hike in risk. It’s entirely possible that there are environmental factors that we don’t yet know about, Norton said. “Controlling for economic status is not the same as controlling for the 5,000 things that people can share,” she said.

Finding the reason for the increased risk of dementia will be the focus for future research.

“We need more studies to determine how much of this association is due to caregiver stress and how much of it might be due to a shared environment,” she said. “It’s possible that we’ll find that there is something that the caregivers who developed dementia had in common, such as a particular personality trait or their coping styles. Or, maybe it isn’t as much about the caregiver so much as it is about the spouse who gets dementia first: how rapidly they decline, whether they have delusions. Not all dementias are the same. Some might be more stressful to the caregiver.”

An expert unaffiliated with the new study called the finding “compelling,” but not necessarily surprising.

“Caregiving is very stressful,” said Dr. Gary W. Small, director of the University of California-Los Angeles, Center on Aging and director of the Geriatric Psychiatry Division at the Semel Institute for Neuroscience and Human Behavior at the David Geffen School of Medicine at UCLA. “Studies have shown that caregivers for dementia patients have a high risk for major clinical depression. And there has been a study that showed that people who are prone to stress are at higher risk for Alzheimer’s.”

Four new connections to PSP/CBD found in genetics study

I don’t know if you all caught what Janet Edmunson (of CurePSP) said at last week’s webinar…

We had heard from Dr. Schellenberg, the lead investigator on the PSP and CBD Genetics Program, back in November that four new genes were found that are implicated in PSP and CBD. These four new genes were discovered by conducting genome wide analyses of 1380 donated brains. (See my earlier November 2009 post on this topic.)

We have at least four local support group members whose loved one’s brains are included in that 1380 pool!

As Dr. Schellenberg indicates in the CurePSP Magazine article copied below, a replication study was to be done with 1000 more PSP cases. This was to be a combination of brain tissue from those with autopsy-confirmed PSP and blood from some still alive who were given PSP diagnoses by a few expert MDs (such as Irene Litvan or Larry Golbe). The replication study was completed a couple of months ago.

We have at least four local support group members whose loved one’s brains were included in that 1000 pool! Three local support group members donated loved one’s brains to local medical institutions not participating in this research.

When Dr. Schellenberg and colleagues did the replication study, they actually came up with six to eight new genes! It depends on the significance threshold. During the webinar, Janet reported that six new genes had been found.

This is wonderful! With this info, hopefully we are on our way to finding some new treatments and some biomarkers (to enable diagnosis while someone is alive) as well as understanding the cause of PSP and CBD and, eventually, prevention of these diseases.

I’ve copied below an article from the most recent CurePSP Magazine about the genetics program. This article mentions the four areas announced back in November 2009.

Thanks to everyone who has donated a loved one’s brain — whether your loved ones were included in this research or not, you may this research possible!



Update on the CurePSP Genetics Program
by Richard G. Zyne, President/CEO of CurePSP
Winter 2010 CurePSP Magazine
(which I received in mid-April 2010)

2009 was a most successful year. Not only did CurePSP raise over $4.5 million in gifts for research and education, but the CurePSP Genetics Consortium made some new and preliminary discoveries which could open doors to possible treatment opportunities.

The Charles D. Peebler, Jr. PSP and CBD Genetics Program, funded by CurePSP, has obtained preliminary, unpublished results in its whole-genome analysis for genetic variants contributing to the causation of PSP and CBD. The two-year project has incriminated four areas of the genome not previously suspected of a relationship to PSP or CBD. Each area includes only one or two genes that could explain the findings. The Genetics Consortium is now embarking on a two-month project to replicate those results in a new set of DNA samples. If confirmed, this work will provide new understanding of the cause of PSP and CBD and allow the development of new targets for disease prevention. It could also permit diagnostic testing to identify candidates for future neuroprotective treatment.

The Charles D. Peebler Jr. PSP and CBD Genetics Program comprises 15 scientists (Genetics Consortium), tasked with the job of finding genes that contribute to the cause of PSP and CBD. The group is chaired by Dr. Gerard Schellenberg, a leading neurogeneticist. On September 1, 2009, Dr. Schellenberg convened a meeting of the Consortium in Philadelphia to review its accomplishments to date and to plan its next moves.

The whole-genome analysis, or WGA, started by collecting DNA samples from brain tissue of 1200 people with PSP whose brains had been donated to brain banks and other research collections in North America and Europe and whose autopsies confirmed the diagnosis. 180 DNA samples from brains with CBD were also collected. As these are both rare diseases, accumulating the required number of samples from autopsy-derived brain tissue required a massive effort. Dr. Schellenberg and his European co-chairman, Dr. Gunter Hoglinger of the University of Marburg, in Germany, convinced 20 colleagues in seven countries to donate DNA samples from their labs’ research collections.

For the next step in the project, another Consortium member, Dr. Hakon Hakonarson of the Children’s Hospital of Philadelphia, a specialist in high-tech, high-volume genetic analytical methods, used a recently available “gene chip” to analyze the DNA samples. Each of the chips’ 555,000 compartments carries the chemicals necessary to tell which version of the gene that varies among healthy humans is carried by each sample. Each of those genes is called a “marker” because they are not themselves harmful, but serve only as flags marking locations evenly spaced over all 23 chromosomes. Each marker takes the form of a single “letter” substituted in the genetic code and is called a “single-nucleotide polymorphism” or SNP, pronounced “snip.” The SNP results for the 1380 PSP/CBD patients are compared with results from a population without neurological disorders that was already in Dr. Hakonarson’s database. A SNP whose variants are found to occur in different proportions between persons with PSP/CBD and those without is considered a “hit.”

The result, eagerly awaited for the two years since the project’s conception, was four very clear hits, none of which had been previously suspected of a connection with PSP/CBD. The statistical strength of the four hits was very high, making it unlikely that the findings occurred purely by chance. Three of the four regions included two adjacent genes, only one of which would [likely] be the true culprit on more detailed analysis that the Consortium plans.

The final results of the replication of this work will be conducted in the winter of 2010 with publication to follow in the spring. We all look forward to the completed project and the publication of the findings in a professional journal. But this may only be the beginning of our understanding of the genetic underpinnings of PSP and CBD that may lead us closer to an eventual prevention or cure.

2010 marks the twentieth anniversary of CurePSP and perhaps we will take a major leap forward to achieving our vision of a world free from PSP and CBD.