Journal article on MRIs to distinguish PSP, MSA, and PD

This article in the Movement Disorder Society magazine (of the UK) is on using MRIs to distinguish between Progressive supranuclear palsy (PSP), Multiple system atrophy (MSA), and Parkinson’s disease (PD). Apparently the technique is most (only?) effective in later stages. This was published online on 4/6/06. The abstract is below.

Robin

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Regional brain volumes distinguish PSP, MSA-P, and PD: MRI-based clinico-radiological correlations
Dominic C. Paviour, MRCP, Shona L. Price, BSc, Marjan Jahanshahi, PhD , Andrew J. Lees, MD, FRCP , Nick C. Fox, MD, FRCP

Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are neurodegenerative disorders, each with a prevalence of around 5 per 100,000. Regional brain atrophy patterns differ in the two disorders, however, and magnetic resonance imaging is sometimes helpful in distinguishing them in the later stages. We measured whole brain and regional volumes, including cerebellum, pons, midbrain, superior cerebellar peduncle (SCP), and ventricular volumes as well as frontal and posterior-inferior cerebral regions in 18 subjects with PSP, 9 with MSA-P (parkinsonian phenotype), 9 with Parkinson’s disease (PD), and 18 healthy controls. Associations between these volumes, cognitive profiles, and clinical measures of disease severity and motor disability were assessed. Mean midbrain volume was 30% smaller in PSP than in PD or controls (P < 0.001) and 15% smaller than in MSA-P (P = 0.009). The mean SCP volume in PSP was 30% smaller than in MSA-P, PD, or controls (P < 0.001). Mean cerebellar volumes in MSA-P were 20% smaller than in controls and PD and 18% smaller than in PSP (P = 0.01). Mean pontine volume in MSA-P was 30% smaller than in PD or controls (P < 0.001) and 25% smaller than in PSP (P = 0.01). Motor disability was most strongly associated with midbrain volume, and more severe executive dysfunction was associated with reduced frontal volume. These distinct patterns of cortical and subcortical atrophy, when considered together rather than independently, better differentiate PSP and MSA-P from each other and also from healthy controls. © 2006 Movement Disorder Society

“Applause sign” to diagnose PSP?

The “applause sign” test is useful in diagnosing progressive supranuclear palsy (PSP), according to recent research.  The “applause sign” is where you ask someone who might have PSP to clap.  While clapping, you tell them to stop.  The person with PSP continues to clap; it takes them awhile to stop.

In a study done by Dubois, 30 out of 42 patients diagnosed with PSP could not stop applauding immediately after being told to stop.  None of those with frontotemporal dementia (FTD) or Parkinson’s Disease (PD) had trouble stopping.

So I guess the part of the brain that controls this process is not affected by PD or FTD…?  The “applause sign” is an indication of “motor perseveration.” Perhaps this is controlled by the frontal lobe so interesting that it’s not affected in FTD.

I’ll ask the neurologist to do this in Dad’s next appt.  I’m interested in seeing this.

Copied below is part of the abstract of the Dubois article (published 6/05 in Neurology) from PubMed (pubmed.gov).

Robin

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“Applause sign” helps to discriminate PSP from FTD and PD

The “applause sign” is a simple test of motor control that helps to differentiate PSP from frontal or striatofrontal degenerative diseases. It was found in 0/39 controls, 0 of 24 patients with frontotemporal dementia (FTD), 0 of 17 patients with Parkinson disease (PD), and 30/42 patients with progressive supranuclear palsy (PSP). It discriminated PSP from FTD (p < 0.001) and PD (p < 0.00). The “three clap test” correctly identified 81.8% of the patients in the comparison PSP and FTD and 75% of the patients in the comparison of PSP and PD.

Arctic ground squirrel clears out tau during hibernation

The PSP Family Conference, put on by the Society for PSP (Progressive Supranuclear Palsy), was held last Saturday near SFO.

As I had attended the ’04 PSP Family Conference and had heard Dr. James Tetrud speak before, I had different expectations of what he would say at this year’s conference.  He is the neurologist at The Parkinson’s Institute who probably knows the most about Atypical Parkinsonism disorders, such as PSP, LBD, MSA, and CBGD.  I compared his slides from ’06 to ’04, and was disappointed that there was nothing new to report in the area of research with one exception:  at last Saturday’s conference he mentioned the Arctic ground squirrel.

During a 7-month hibernation, the squirrel’s brain loses many of the nerve-cell connections that govern how it operates.  Tau protein accumulates in the brain — just like with Alzheimer’s Disease and PSP.  (I’m sorry to say that I don’t know the pathology of the other Atypical Parkinsonism diseases.)  Within 2 to 3 hours of emerging from hibernation, there is a wave of neuronal growth and tau is eliminated.  Thus, there appears to be a mechanism to clear tau.

Dr. Tetrud referred to a recent Economist magazine article on the subject.  I consider myself to have excellent follow-through and research skills but I was outdone on both of these fronts by Sam, a support group member who also attended the Saturday conference.  He found the article in the Feb. 4th issue (page 72).  Here’s a link to the article:

www.economist.com/node/5466196

Dementia
Sleeping on it
Similarities between dementia and hibernation suggest a treatment
The Economist
Feb 2nd 2006

It’s interesting reading!  Let’s hope something comes of it…

Robin

Points from an expert physical therapist – on PD and parkinsonism

I attended Marilyn Basham’s presentation this afternoon on “Caregiving Made Easy for Parkinson’s Individuals.”  She’s the physical therapist (PT) at The Parkinson’s Institute (TPI).  I picked up a few tidbits at the presentation that I thought I’d pass along.  As the presentation was focused on Parkinson’s Disease (PD), not everything applied to the situations we are dealing with but there were still many interesting points that apply.

Here are the points I found interesting….  (with some of my comments in parantheses)

People with PD and Parkinsonism MUST use a walker or wheelchair to make them as safe as possible.  It’s very important to have mobility and postural strategies worked out with a physical therapist and/or neurologist.

PD is evident when 60-80% of the cells in the basal ganglia have died.

The “automatic motor programs” we have are stored in the basal ganglia.  One of these “programs” is what tells us that to stand up from a low chair, we need to scoot to the edge, put our feet underneath us, lean forward, and push up.  PD folks must either receive cues as to the steps of these programs, or they must practice it so many times that doing it becomes somewhat automatic again.

To overcome freezing (called “gait initiation failure”), you can put masking tape on the floor to provide a visual cue.  Put the tape at thresholds or where ever the person often has the freezing problem.  (Of course this won’t work for those with PSP who have downward gaze palsy.)

A suggested verbal cue to give someone who wants to speak is:  “Swallow.”  (pause to let the person swallow)  “Take a deep breath in and then, at the top of your breath tell me what you want.”  (pause to let this happen)  Swallowing is important because fluid accumulates in the back of the throat and those with PD are not aware of it.  You can give them gum to initiate a swallow response.

Before someone with MSA (or PD with blood pressure fluctuations) stands up, give them a glass of water with salt in it or Gatoraid.  This will increase the blood pressure.  Obviously the person’s diet and blood pressure medication needs to be taken into account before following this suggestion.

We must give time for those with these diseases to process information!  Be patient!  Give long pauses.  Don’t overload them.  Don’t give them more than one complex task at a time.  Walking is a complex task.

(Some of you know that my father and I communicate by our holding up fingers to designate an answer.  Example, “do you want 1 for coffee, 2 for tea, or 3 for nothing,” and I hold up 1, 2, and 3 fingers.  He answers by holding up fingers.  Long after the fingers come up, he may try to verbalize the answer.)  I asked Marilyn why my father could hold up fingers faster than he could verbalize a response.  Marilyn said she didn’t know why but pointed out that parents of small children teach their children sign language long before the children can verbalize.

Dementia is rare in PD.  (It’s definitely common in the Atypical Parkinsonism diseases.)  PD folks may lose their keys but they still remember what keys are and how to use them.  (I thought that was a good story for remembering what dementia is.  My dad, for example, cannot remember how to use an ATM card.  I see the dementia very clearly.)

A patch for Sinemet is in the works.  (Some of your loved ones take Sinemet.)

The head of TPI thinks that PD is the most curable of all the neurodegenerative diseases.  (Let’s hope he’s right because hopefully those diseases related to PD can be cured quickly too.)

Regards,
Robin

Theoretical benefit of DBS with PSP and MSA

For those with not enough reading materials(!), neurologyreviews.com is an interesting website.  In the January 2006 News Roundup section of the website, there’s an article about how deep brain stimulation in specific areas could help those with multiple system atrophy or progressive supranuclear palsy.

A short blurb is copied below.

Robin

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www.neurologyreviews.com/jan06/newsroundup.html

Two studies in the November 28, 2005, NeuroReport demonstrated that the pedunculopontine nucleus can be targeted safely and effectively with deep brain stimulation without major surgical risks in patients with Parkinson’s disease. Low frequency (20 to 25 Hz) stimulation of the pedunculopontine nucleus improves postural stability and gait disturbance, including “on-medication” freezing. Furthermore, combined stimulation of the subthalamic nucleus and the pedunculopontine nucleus appears to be more valuable than stimulation of the pedunculopontine nucleus alone. “In theory, even patients with multiple system atrophy or progressive supranuclear palsy could benefit [from this treatment]­in fact, any patient with intractable locomotive and postural akinesia [could benefit],” reported the investigators.

Differentiating CBD syndrome from PSP using brain atrophy patterns

Sharon, one of our group members, sent this to me today.  It’s an article about a study done at UCSF that shows that the patterns of brain atrophy are different in progressive supranuclear palsy and corticobasal degeneration.

Many of your loved ones see neurologists at UCSF. In fact, Sharon’s husband is one of the PSP patients in the study.

The abstract is copied below.

Robin


Archives of Neurology, January 2006, Vol. 63 No. 1

Patterns of brain atrophy that differentiate corticobasal degeneration syndrome from progressive supranuclear palsy.

Boxer AL, Geschwind MD, Belfor N, Gorno-Tempini ML, Schauer GF, Miller BL, Weiner MW, Rosen HJ
Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94143-1207, USA. [email protected]

BACKGROUND: Progressive brain atrophy is associated with the corticobasal degeneration syndrome (CBDS) and progressive supranuclear palsy (PSP). Regional differences in brain atrophy may reflect the clinical features of disease.

OBJECTIVE: To quantify the structural neuroanatomical differences between CBDS and PSP.

DESIGN: A survey of neurologic deficits was conducted in all patients. Voxel-based morphometry was used to quantify structural neuroanatomical differences on magnetic resonance images in each subject group. SETTING: University hospital dementia clinic.

PARTICIPANTS: Fourteen patients who met clinical research criteria for CBD and 15 patients who met clinical research criteria for PSP, who were matched for severity of disease, age, and functional status, and 80 age-matched control subjects.

MAIN OUTCOME MEASURES: Statistically significant differences in regional gray and white matter volume, after multiple comparisons correction, between groups of subjects.

RESULTS: The patients with CBDS displayed an asymmetric (left > right) pattern of brain atrophy that involved the bilateral premotor cortex, superior parietal lobules, and striatum. Progressive supranuclear palsy was associated with atrophy of the midbrain, pons, thalamus, and striatum, with minimal involvement of the frontal cortex. Midbrain structures were more atrophied in PSP than in CBD, whereas dorsal frontal and parietal cortices were more atrophied in CBD than in PSP. The degree of atrophy of the midbrain and pontine tegmentum and the left frontal eye field differentiated the 2 patient groups with 93% accuracy.

CONCLUSIONS: Distinct patterns of brain atrophy exist in CBDS and PSP that can be used to differentiate the 2 diseases. Assessments of brain atrophy in these disorders should be focused on cortical and brainstem ocular motor control areas.

 

PSP and MSA can occasionally co-exist

An article was published earlier this week in a medical journal for neuropathologists.  Here’s the key point of this abstract:

“Based upon the findings in this case, the neuropathologic changes of PSP and MSA are distinct and independent processes, but they can occasionally coexist.”

Obviously these things can ONLY be known through brain donation.  I hope everyone in our group will consider that.

I’ve copied the full abstract below.

Robin


Acta Neuropathologica (Berlin).  2006 Feb 3; 1-7.

Coexistence of PSP and MSA: a case report and review of the literature.

Uchikado H, Delledonne A, Uitti R, Dickson DW

Department of Neuroscience, Neuropathology Laboratory, Mayo Clinic, 4500 San
Pablo Road, Jacksonville, FL, 32224, USA,  [email protected]

Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy characterized by Parkinsonism, vertical gaze palsy,  and early falls. The neuropathology is characterized by neurofibrillary tangles, tufted astrocytes, and
coiled bodies, but some brains show other pathologic processes. To investigate the frequency of alpha-synuclein pathology in PSP with immunohistochemistry and to report the clinical and pathological features of a case of PSP with
concomitant Multiple system atrophy (MSA) (PSP/MSA), 290 cases of PSP were screened for alpha-synuclein pathology withi mmunohistochemistry.  Double-labeling
immunohistochemistry was performed on a case of PSP/MSA. Among the PSP cases screened for alpha-synuclein pathology, a single case of PSP/MSA  was detected. The patient was an 86-year-old woman with clinical features consistent with PSP. She had no documented dysautonomia or cerebellar signs, and imaging studies were not diagnostic of MSA. Pathological examination showed tau-immunoreactive neuronal and glial lesions consistent with PSP as well as alpha-synuclein immunoreactive glial cytoplasmic inclusions diagnostic of MSA. Double-immunolabeling studies showed no co-localization of alpha-synuclein and tau in
most neuronal and glial lesions. Based upon the findings in this case, the neuropathologic changes of PSP and MSA are distinct and independent processes, but they can occasionally coexist.

 

Advance Notice: 4/8/06 PSP Family Conference

I just got word this morning that there will be a PSP Family Conference in the SF Bay Area on Saturday 4/8/06.  It is being put on by the Society for PSP.  It will be held either in SF or somewhere near SFO.  We are being asked to offer suggestions on location and speakers, so let me know if you have any thoughts.  The ’04 conference was attended by 100 people.  The expectation is that this year’s conference will have even more attendees as there is a chance an announcement will be made about a Hollywood personality becoming a spokesperson for the Society for PSP.  I thought the location of the ’04 conference was good (UCSF conference center) and suggested that again.  Hotels, in general, will be more expensive unless we have an “in.”  I thought the UCSF speaker last time on swallowing issues did a great job.  In particular, the Society for PSP is looking for practically-oriented speakers (like speech therapists, swallowing specialists, OTs, and PTs).  I’ll keep you posted as I learn more.
Robin

 

Two distinct types of PSP – RS and PSP-parkinsonism

Here’s the citation to a very important paper published recently on progressive supranuclear palsy (PSP):

Brain. 2005 Jun;128(Pt 6):1247-58. Epub 2005 Mar 23. 
Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson’s syndrome and PSP-parkinsonism.
Williams DR, de Silva R, Paviour DC, Pittman A, Watt HC, Kilford L, Holton JL, Revesz T, Lees AJ.
The Queen Square Brain Bank for Neurological Disorders, University College London, UK.

Dr. David Williams and others from The Queen Square Brain Bank in London examined the brains and clinical records of 103 people with autopsy-confirmed PSP.  They discovered two key clinical types of PSP:  Richardson’s Syndrome and PSP-parkinsonism.

The authors described Richardson’s Syndrome (RS) as follows:

“The core clinical features of PSP appears to be bradykinesia, rigidity and postural instability, and are almost always present later in the disease.  Together with the supranuclear vertical ophthalmoplegia, dementia, dysarthria and pseudobulbar palsy, they form the classic features of PSP.  When these features appear in the first 2 years, a diagnosis of RS is most likely.”

The authors described the PSP-parkinsonism type as follows:

“The features which most clearly differentiate this syndrome from RS appear to be an asymmetric onset, extra-axial dystonia, tremor and benefit from levodopa.  Early bradykinesia appears to be essential for the diagnosis, but does not adequately differentiate it from RS, especially later in the disease course.  Disease duration in PSP-P is significantly longer than in RS, and to our knowledge exceeds median survival in all clinicopathological PSP case series.”

Here’s the abstract to this important paper:  (broken into paragraphs)

“The clinical diagnosis of progressive supranuclear palsy (PSP) relies on the identification of characteristic signs and symptoms. A proportion of pathologically diagnosed cases do not develop these classic features, prove difficult to diagnose during life and are considered as atypical PSP. The aim of this study was to examine the apparent clinical dichotomy between typical and atypical PSP, and to compare the biochemical and genetic characteristics of these groups.

In 103 consecutive cases of pathologically confirmed PSP, we have identified two clinical phenotypes by factor analysis which we have named Richardson’s syndrome (RS) and PSP-parkinsonism (PSP-P). Cases of RS syndrome made up 54% of all cases, and were characterized by the early onset of postural instability and falls, supranuclear vertical gaze palsy and cognitive dysfunction. A second group of 33 (32%) were characterized by asymmetric onset, tremor, a moderate initial therapeutic response to levodopa and were frequently confused with Parkinson’s disease (PSP-P). Fourteen cases (14%) could not be separated according to these criteria. In RS, two-thirds of cases were men, whereas the sex distribution in PSP-P was even. Disease duration in RS was significantly shorter (5.9 versus 9.1 years, P < 0.001) and age at death earlier (72.1 versus 75.5 years, P = 0.01) than in PSP-P.

The isoform composition of insoluble tangle-tau isolated from the basal pons also differed significantly. In RS, the mean four-repeat:three-repeat tau ratio was 2.84 and in PSP-P it was 1.63 (P < 0.003). The effect of the H1,H1 PSP susceptibility genotype appeared stronger in RS than in PSP-P (odds ratio 13.2 versus 4.5). The difference in genotype frequencies between the clinical subgroups was not significant. There were no differences in apolipoprotein E genotypes.

The classic clinical description of PSP, which includes supranuclear gaze palsy, early falls and dementia, does not adequately describe one-third of cases in this series of pathologically confirmed cases. We propose that PSP-P represents a second discrete clinical phenotype that needs to be clinically distinguished from classical PSP (RS). The different tau isoform deposition in the basal pons suggests that this may ultimately prove to be a discrete nosological entity.”

From my reading, the PSP-parkinsonism type of PSP looks like Parkinson’s Disease and may look like MSA, specifically the parkinsonism type (MSA-P).

According to the full article, some people with PSP actually had a response to levodopa therapy!  Do the diagnostic criteria need to be changed to accommodate this finding?

Robin


Update from 2007:

This important paper is now available online at no cost.

Here’s the direct link to the Brain ’05 article:

brain.oxfordjournals.org/cgi/reprint/128/6/1247

And I think the commentary is worth reading too:

brain.oxfordjournals.org/cgi/reprint/128/6/1235

 

Large display clock

This is in the category of a small tip….

My dad (with PSP) had been getting up in the middle of the night, thinking it was morning.  Probably most of the time this happened he fell because he’s very tired and unsteady on his feet at the wee hours.  Over half of his falls used to occur at 3am or 4am.  I had been addressing the “cause” of the falls.  For example, he would often fall at 3am while putting on his robe in the bathroom.  I moved the robe to right next to his bed so he can put it on while sitting down.  But then I addressed the larger issue of why he gets up in the middle of the night.  I learned that he could not read the time on his alarm clock any more.  The display was too small.

I went to the Peninsula Center for the Blind and Vision Impaired (PCBVI) in Palo Alto, CA and found a large display clock for $26.75.  Their supplier is MaxiAids (www.maxiaids.com or 800-522-6294), who sells the clock for the same price.  It’s item #74852 – AM-FM Clock Radio with Extra Large LED Display.  The numbers are green.  Turns out that some low-vision people can see green better than they can white or red.  Anyway, this clock solved the problem of not knowing what time it was in the middle of the night.  Dad no longer gets up at 3am or 4am so those falls have been eliminated.  (Unfortunately there’s still lots of other falling!)

The PCBVI and MaxiAids also have clocks that talk (say the time).  We might have to go that route if Dad’s vision problems worsen.

Robin