“Unraveling PSP” article (by Houghton/Litvan)

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In this short abstract, the authors state: “Etiology remains elusive, but a variable combination of genetic, environmental, oxidative stress, and inflammatory factors may all contribute.” (etiology = cause)
Robin

Parkinsonism & Related Disorders. 2007;13 Suppl 3:S341-6.

Unraveling progressive supranuclear palsy: from the bedside back to the bench.

Houghton DJ, Litvan I.
Division of Movement Disorders, Department of Neurology, University of Louisville, Louisville, KY, USA.

Progressive supranuclear palsy (PSP) typically presents with a gradual onset and progressive course of symmetric levodopa-unresponsive parkinsonism characterized by postural instability with falls, supranuclear vertical gaze palsy, dysarthria, dysphagia, and cognitive and behavioral disturbances.

Though the clinical course is variable, the typical presentation is usually associated with mortality at 5-9 years after symptom onset.

The pathological hallmark of PSP is widespread neuronal cell loss with deposition of aggregated hyperphosphorylated tau, particularly within the midbrain.

Etiology remains elusive, but a variable combination of genetic, environmental, oxidative stress, and inflammatory factors may all contribute.

Genetic advances have confirmed the H1 tau haplotype on chromosome 17q21.31 to be associated with PSP, while the H2 haplotype seems protective. With greater knowledge of the molecular and genetic aspects of PSP, we can expect future diagnostic and therapeutic challenges to be more effectively met.

PubMed ID#: 18267262 (see pubmed.gov for abstract only)

Brain-Computer Interface for Communication (60 Minutes10/31)

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A local support group member sent me this link to an amazing “60 Minutes” segment from last Sunday called “Brain Power.” A man with ALS (diagnosed in ’99) and a woman who had a stroke — both of whom are “locked-in” (fully functioning minds locked in disabled bodies) — are shown using their thoughts to communicate and use a computer. The man, Dr. Scott Mackler*, is a neuroscientist who is still able to run a research lab at the University of Pennsylvania. The woman also uses her mind to operate a wheelchair. It’s incredible.

The link is: (you may have to cut and paste to get the link to fit on one line)
http://www.cbsnews.com/stories/2008/10/ … 0940.shtml

Robin

* Someone on an MSA-related discussion group posted these two links for previous media coverage of Dr. Mackler:

http://www.alsphiladelphia.org/NetCommu … Doc?id=198

http://www.philadelphiaweekly.com/view.php?id=9839

NPH Commonly Misdiagnosed as PD, Atypical Parkinsonism or AD

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Good Morning America (on ABC) had a segment this Thursday on NPH (normal pressure hydrocephalus). (Janet Edmunson alerted me to this segment.) Common symptoms in NPH are gait problems (shuffling), urinary incontinence, memory problems, and slowed thinking. Some of these symptoms can also be found in the four atypical parkinsonism disorders. I have occasionally read about people being diagnosed with PSP, CBD, MSA, or LBD initially, and then MDs figure out it is actually NPH. (I’ve probably read about more cases that go the other way: initial diagnosis of NPH, and a later diagnosis of an atypical parkinsonism disorder.) According to this GMA segment, NPH can be misdiagnosed as Alzheimer’s or Parkinson’s Disease. An MRI is critical in diagnosing NPH. This is one of the few dementia-causing conditions that is treatable.

Here’s a link to the video of the GMA segment:
http://abcnews.go.com/Video/playerIndex?id=6196343
(You’ll have to watch a short commercial beforehand. And the volume is set *very* high for both the ad and the segment; you can turn it down.)

At the bottom of this post is a transcript of the Good Morning America segment. Here’s a link to the transcript:
http://abcnews.go.com/GMA/OnCall/story? … 680&page=1

Finally, you can locate info on NPH here:
http://www.lifenph.com/
http://www.emedicine.com/neuro/topic277.htm

Is It Really Alzheimer’s?
NPH Commonly Is Misdiagnosed as Alzheimer’s Disease
By JUJU CHANG, THEA TRACHTENBERG and IMAEYEN IBANGA
Good Morning America (ABC News)

Nov. 6, 2008 —

When 74-year-old Phil Myers was barely able to walk and his memory seemed to be going quickly, his wife, Shirley Myers, was terrified. She watched as the man she loved and was married to for 54 years slipped away, with thoughts of the two children they’d raised clearly in her mind.

“At first I was scared,” Shirley Myers said. “He took care of his family. He was just a family man. That was it. And he did so much for me.”

Is It Alzheimer’s?
“The doctors kept saying, ‘Oh, he’s OK. He’s OK,’ but then things kept getting worse — like dragging his feet. And then he started kind of forgetting where he was at,” Shirley Myers said.

The first diagnosis doctors gave Phil Myers was devastating; they believed it was a form of Alzheimer’s.

“When they told me it was Alzheimer’s, I couldn’t believe it because he was only 70 years old and it just didn’t seem like it was his time yet,” Shirley Myers said.

So the two went to see neurologist Mark Luciano from the Cleveland Clinic. He suspected it wasn’t Alzheimer’s at all, but rather something called normal pressure hydrocephalus, or NPH.

What Is NPH?
According to “Good Morning America” medical editor Dr. Tim Johnson, NPH can begin at age 55 and no one knows why.

The condition occurs when cerebral spinal fluid accumulates in the brain. The extra fluid pushes the brain against the nerves that affect memory, walking and balance, and bladder control.

“Hydrocephalis just means water inside the brain. It’s when water builds up and starts pressing on the brain itself,” Luciano said.

“The symptoms come on very gradually and they can be very subtle,” he said. “A gait problem, a problem with your bladder control, a problem with your memory, those are all very common symptoms in our elderly population.”

Other symptoms include problems with thinking, a slowing down of the thought process. Since the symptoms are so common, the condition is often misdiagnosed.

That happens in part because the warning signs come on very gradually and they can be very subtle, Johnson said. Also, in the elderly population, loss of memory, walking slowly, bladder control problems are all very common problems, so it looks like many other diseases, such as Parkinson’s, Alzheimer’s or dementia, he added.

“It is one of the only treatable forms of dementia or memory loss. It can be not only treated, but in many cases reversed to a great extent just by removing the fluid,” Luciano said.

An MRI of the brain will show the enlarged ventricles and is a way for doctors to properly diagnose the condition, Johnson said.

Treatment of NPH
Treatment for NPH is a relatively simple operation.

“When they told us it was — it would be treatable, it was like a miracle,” Shirley Myers said. “We all felt like it’s a miracle.”

A shunt is implanted in the brain and leads the excess fluid away from the brain and into the abdomen.

“Quite honestly, we weren’t sure that fluid removal was going to help him,” Luciano said.

Four months ago, Phil Myers had the operation to implant the shunt, four years after his symptoms first appeared.

Now the man, who once had tremendous trouble walking, travels with much more ease.

“It was quite, quite nice to be able to do the things you want to do,” he said.

Phil Myers remains in recovery and Luciano said it can take up to a full year to see all the effects of the procedure.

“The improvement that we see now, we hope, that he has for many years,” Luciano said.

“He still has a ways to go on some issues, but his walking is terrific. And that’s what the doctor was looking for I think. And his balance has improved,” Shirley Myers said.

Click here to get more information about NPH: http://www.lifenph.com/

“Tau forms in CSF as a reliable biomarker” for PSP

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This is a GREAT Italian study (just published last week) on the use of CSF (cerebrospinal fluid) in diagnosing PSP. The researchers found: “Truncated tau production, which selectively affects brainstem neuron susceptibility, can be considered a specific and reliable marker for PSP.”

“A total of 166 subjects were included in the study (21 PSP, 20 corticobasal degeneration syndrome, 44 frontotemporal dementia, 29 Alzheimer disease, 10 Parkinson disease, 15 dementia with Lewy bodies, and 27 individuals without any neurodegenerative disorder). Each patient underwent a standardized clinical and neuropsychological evaluation. In CSF, a semiquantitative immunoprecipitation was developed to evaluate CSF tau 33 kDa/55 kDa ratio. MRI assessment and VBM analysis was carried out.” Researchers concluded that “Tau form ratio was the lowest in progressive supranuclear palsy with no overlap with any other neurodegenerative illness.”

If this can be duplicated and if the clinical diagnoses of the 166 subjects involved in the study can be confirmed on post-mortem analysis, we will have a biomarker for diagnosing PSP.

I’m pretty sure this is the paper that Dr. Golbe was referring to in the PSP/CBD webinar a few weeks ago.

Robin

Neurology. 2008 Oct 29. [Epub ahead of print]

Tau forms in CSF as a reliable biomarker for progressive supranuclear palsy.

Borroni B, Malinverno M, Gardoni F, Alberici A, Parnetti L, Premi E, Bonuccelli U, Grassi M, Perani D, Calabresi P, Di Luca M, Padovani A.

From the Centre for Aging Brain and Dementia (B.B., A.A., E.P., A.P.), Department of Neurology, University of Brescia; the Centre of Excellence for Neurodegenerative Disorders and Department of Pharmacological Sciences (M.M., F.G., M.D.), University of Milan; the Section of Clinical Neuroscience (L.P., P.C.), University of Perugia; Department of Neurology (U.B.), University of Pisa; Department of Health Sciences (M.G.), Section of Medical Statistics & Epidemiology, University of Pavia; and the Vita-Salute San Raffaele University and Scientific Institute San Raffaele (D.P.), Milan, Italy.

OBJECTIVE: In CSF, extended (55 kDa) and truncated (33 kDa) tau forms have been previously recognized, and the tau 33 kDa/55 kDa ratio has been found significantly reduced in progressive supranuclear palsy (PSP) vs in other neurodegenerative disorders.

The aim of this study was to evaluate the diagnostic value of the CSF tau form ratio as a biomarker of PSP and to correlate the structural anatomic changes as measured by means of voxel-based morphometry (VBM) to CSF tau form ratio decrease.

METHODS: A total of 166 subjects were included in the study (21 PSP, 20 corticobasal degeneration syndrome, 44 frontotemporal dementia, 29 Alzheimer disease, 10 Parkinson disease, 15 dementia with Lewy bodies, and 27 individuals without any neurodegenerative disorder). Each patient underwent a standardized clinical and neuropsychological evaluation. In CSF, a semiquantitative immunoprecipitation was developed to evaluate CSF tau 33 kDa/55 kDa ratio. MRI assessment and VBM analysis was carried out.

RESULTS: Tau form ratio was significantly reduced in patients with PSP (0.504 +/- 0.284) when compared to age-matched controls (0.989 +/- 0.343), and to patients with other neurodegenerative conditions (range = 0.899-1.215). The area under the curve (AUC) of the receiver operating characteristic analysis in PSP vs other subgroups ranged from 0.863 to 0.937 (PSP vs others, AUC = 0.897, p < 0.0001). VBM study showed that CSF tau form ratio decrease correlated significantly with brainstem atrophy.

CONCLUSIONS: Truncated tau production, which selectively affects brainstem neuron susceptibility, can be considered a specific and reliable marker for PSP. Tau form ratio was the lowest in progressive supranuclear palsy with no overlap with any other neurodegenerative illness.

PubMed ID#: 18971445 (see pubmed.gov for abstract only)

Giving PSPers balance exercises w/and w/o eye exercises

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This is an interesting little study done in Beaverton, OR and published last week in the journal “Physical Therapy.”  Ten people with the clinical diagnosis of progressive supranuclear palsy (PSP) were given balance training and eye movement exercises (“treatment group”) while nine people with PSP were given balance training only (“comparison group”).

Results were:

“The within-group analysis revealed significant improvements in stance time and walking speed for the treatment group, whereas the comparison group showed improvements in step length only.”

The abstract is copied below.

Robin
————————————

Physical Therapy 2008 Oct 23. [Epub ahead of print]

Balance and Eye Movement Training to Improve Gait in People With Progressive Supranuclear Palsy: Quasi-Randomized Clinical Trial.

Zampieri C, Di Fabio RP.
Neurological Science Institute, Oregon Health and Science University, Beaverton, OR.

BACKGROUND AND PURPOSE: Although vertical gaze palsy and gait instability are cardinal features of progressive supranuclear palsy (PSP), little research has been done to address oculomotor and gait rehabilitation for PSP.

The purpose of this study was to compare the benefits of a program of balance training complemented with eye movement and visual awareness training versus balance training alone to rehabilitate gait in people with PSP.

Participants Nineteen people moderately affected by the disease were assigned to either a treatment group (balance plus eye movement exercises, n=10) or a comparison group (balance exercises only, n=9) in a quasi-random fashion.

METHODS: The baseline characteristics assessed were diagnosis (possible versus probable), sex, age, time of symptom onset, dementia, and severity of symptoms. Within-group, between-group, and effect size analyses were performed on kinematic gait parameters (stance time, swing time, and step length) and clinical tests 8-ft [2.4-m] walk test and Timed “Up & Go” Test).

RESULTS: The within-group analysis revealed significant improvements in stance time and walking speed for the treatment group, whereas the comparison group showed improvements in step length only. Moderate to large effects of the intervention were observed for the treatment group, and small effects were observed for the comparison group. The between-group analysis did not reveal significant changes for either group.

DISCUSSION AND CONCLUSION: These preliminary findings support the use of eye movement exercises as a complementary therapy for balance training in the rehabilitation of gait in people with PSP and moderate impairments. Additional studies powered at a higher level are needed to confirm these results.

PubMed ID#: 18948373  (see pubmed.gov for the abstract only)