Category Archives: CBD

Ask the Doctor – diseases mistaken for PSP

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Here’s the “Ask the Doctor” section of the Fall ’08 CurePSP Magazine, which I received in the mail on 12/1/08: (not yet available on psp.org)

Ask the Doctor
Lawrence I. Golbe, MD
Director of Research and Clinical Affairs, CurePSP
CurePSP Magazine, Fall ’08

Q: I’ve heard that some people with a diagnosis of PSP actually have corticobasal degeneration. Should I worry about that and get another opinion on my diagnosis?

A: No. PSP and corticobasal degeneration (CBD) are very similar and some experts think they’re even two versions of the same basic disease. They are treated similarly, start at the same average age, have the same long-term prognosis and even share a specific genetic variant as a contributing factor. The difference is that in CBD, there is less falling than in PSP but more difficulty in using the limbs for fine movement. CBD also tends to develop minor jerking movements and abnormal postures of the limbs. The limb problems of CBD are typically highly asymmetric — that is, far worse on one side than the other. All of the symptoms of both PSP and CBD are treated “palliatively,” which means that if the symptom appears, the doctor treats it as a symptom. Some day, if we are able to cure or slow the progression of one but not the other, or if the cures for the two disorders are different, then it will be important to differentiate between the two diagnostically.

Q: OK, so are there any diseases that have cures or very useful treatments that can be mistaken for PSP?

Parkinson’s disease (PD) is sometimes mistaken for PSP when it fails to respond to levodopa, a drug that replaces insufficient brain dopamine. Often, this is simply the result of insufficient dosing. Very often patients with PD have difficulty looking in the upward direction. The combination of this with a much greater-then-average need for levodopa can fool an inexperienced physician into diagnosing PD as PSP. But PD would not display difficulty looking down, the cardinal feature of PSP, and differs in most other respects as well.

Another condition that can be mistaken for PSP and requires special treatment is multiple small strokes. Aggressive management of lipids and blood pressure, administration of blood thinners, repair of narrowed arteries feeding the brain and treatment of heart problems can all reduce the risk of future strokes.

Finally, a very rare brain infection called Whipple’s disease can superficially mimic PSP. However, it usually has rhythmic movements of the eyes and jaw that are absent in PSP. It is diagnosed via MRI with contrast and a spinal tap and treated with antibiotics. In 20 years as a PSP specialist, I have never seen a case.

“Tools for Meal Time” – good article on dysphagia

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The Fall 2008 CurePSP Magazine (psp.org) has a good article on swallowing problems that may be of interest to everyone — not just those dealing with PSP (progressive supranuclear palsy).

I’ve copied the full text below.  At some point, the newsletter will be available on psp.org; I received it in the mail this week.  You can sign up online at psp.org to receive a copy of future newsletters in the mail.

Robin

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Tools for Meal Time
Laura Purcell Verdun, MA, CCC
Speech-Language Pathologist
Otolaryngology Associates, PC
Fairfax, VA

CurePSP Magazine
Fall 2008 Issue

Difficulty swallowing, or dysphagia, is commonly associated with many neurodegenerative diseases, specifically PSP or CBD.  In fact, difficulty swallowing may be one of the early symptoms of this disorder.  Given that complications related to difficulty swallowing are one of the most common causes of mortality, attention needs to be directed towards optimizing the ease and safety of swallowing.

What changes in eating and swallowing should we look for?

There are actually fairly typical behavioral changes with eating in PSP and CBD.  These often include difficulty looking down at the plate, mouth stuffing and rapid drinking, difficulty with self-feeding because of tremor or stiffness, restricted head and neck posture, and occasional difficulty opening the mouth.  These behaviors can make it more difficult to swallow and often contribute to decompensation of the swallowing mechanism resulting in coughing and choking.  Caregivers need to look out for these behaviors, because the person with PSP or CBD often is not aware of these changes.

What are some tools that we can use to help make meal times more successful?

1.  Use a suction machine, toothette swab (a pink or green sponge on a lollipop-type stick), or mouth rinse prior to meals to clear out secretions which may interfere with ease of swallowing.

2.  A firm chair with arms to support sitting upright for proper swallowing alignment is most ideal.

3.  Keep the plate in the line of vision, by placing the plate on top of a book or something similar, or substituting reading glasses for bifocals.

4.  Try experimenting with different plates and utensils.  Plates with higher edges and bottom grips enhance independence with eating.  Downsize eating utensils to limit how much food is being put in per mouthful.

5.  Experiment with different cups and glasses.  Some are just easier to drink out of than others, depending on a handle or even the thickness and shape of the lip.  Straws are generally not preferred because it results in acceleration of the liquid into the throat before it’s ready.

6.  Use a blender or food processor.  The goal is not to eliminate foods necessarily, but consider how they could be prepared difficultly to enhance ease and safety of swallowing.  Multiple consistency items such as fruit cocktail and broth based soups generally should be avoided, so blend them.

7.  A teaspoon can be used to restrict the amount of liquid placed in the mouth for each swallow.

Though clearly not a comprehensive list, here are some specific products that may be of benefit at meal times.  Look for other products available on these web sites as well:

Flexi-Cut Cup allows for drinking without extending the head and neck backwards, 3 sizes available (800/225-2610, www.alimed.com).

Provale Cup restricts the volume of liquid allowed per swallow (800/225-2610, www.alimed.com).

Maroon Spoons have a narrow shallow bowl to restrict how much food is placed on the spoon and in the mouth, come in 2 sizes (800/897-3202, www.proedinc.com). [Robin’s note:  that’s the correct website!  You can also find these spoons at AliMed.]

Less Mess Spoon is designed with holes to keep food on the spoon, or drain away liquid from a multiple consistency food item (800/257-5376, www.theraproducts.com).

Scooper Plate with Non-Skid Base has a high curve to help scoop food onto a utensil (913/390-0247, www.bindependent.com).

Skidtrol Non-Skid Bowl is a melamine bowl with non-skid base (972/628-7600, www.maddak.com).

Are there any cookbooks that may give us some ideas regarding meal preparation for people with trouble swallowing?

Achilles E and Levin T.  The Dysphagia Cookbook.  2003.  Cumberland House Publishing.

MEALS for Easy Swallowing.  2005.  Muscular Dystrophy Association Publications.  [Robin’s note:  the correct link to this book is www.als-mda.org/publications/meals/ The full contents of this book, including the recipes, are available online.]

Weihofen D, Robbins J, Sullivan P.  Easy-to-Swallow Easy-to-Chew Cookbook.  2002.  John Wiley & Sons, Inc.

Wilson JR and Piper MA.  I Can’t Chew Cookbook: Delicious Soft Diet Recipes for People with Chewing, Swallowing, and Dry-Mouth Disorders.  2003.  Hunter House, Inc.

Woodruff S and Gilbert-Henderson L.  Soft Foods for Easier Eating Cookbook: Recipes for People who have Chewing and Swallowing Difficulties.  2007.  Square One Publishers.

If you have any concerns regarding swallowing, be sure to discuss this further with your neurologist and speech pathologist.

 

5 CBD research grants; NAP is focus of UCSF, UPenn, MayoRoch

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In August ’08, it was announced that the Pollin family had given over $1 million to CurePSP to fund CBD research. (We discussed that here: http://forum.psp.org/viewtopic.php?t=7499)

CurePSP recently announced that a total of $1.15 million in research grants have been given to:
* Mt. Sinai School of Medicine, NY, Dr. Giulio Pasinetti
* University of South Florida, Tampa, Dr. Chad Dickey
* UCSF, San Francisco, Dr. Adam Boxer
* Duke University Med Ctr, Durham, Dr. Hana Dawson
* Cleveland Clinic, Cleveland, Dr. Kiran Bhaskar
(See http://www.psp.org/doc_library/1226690767/cbd%20pr.pdf for the short press release.)

The remainder of this post is about the research that will be conducted at UCSF, UPenn, and Mayo Rochester, hopefully beginning in April ’09.

Dr. Boxer, a neurologist at UCSF’s Memory & Aging Clinic, said that in the spring of 2009 UCSF intends to conduct a trial in CBD (and FTLD) patients with a drug called NAP. He needs to go through the UCSF IRB first as well as the FDA. The research project that Dr. Boxer will manage will potentially include two additional sites — UPenn (with whom UCSF has a close working relationship) and Mayo Rochester. UPenn and Mayo Rochester will also have to go through their IRBs.

(CBD folks can see some preliminary details that I posted recently on the CBD-related Yahoo!Group.)

I posted in late July about news out of the Alzheimer’s conference regarding the experimental drug Rember. (To re-live that news, see http://forum.psp.org/viewtopic.php?p=39893)

Like Rember, NAP is a tau-busting drug. It was also announced at the Alzheimer’s conference (ICAD) in Chicago. A trial of a NAP-derived compound called AL-108 was organized by a Duke University researcher. The drug was administered via a nasal spray for a twelve-week period in those with aMCI (amnesic mild cognitive impairment), thought to be a possible precursor to Alzheimer’s Disease. After four weeks of using the nasal spray, aMCI patients showed improvements in the ability to count backwards and to remember four objects. Here’s a short Good Morning America (ABC News) clip on this treatment from 7/29/08:
http://abcnews.go.com/GMA/story?id=5469940 (you may have to click on “Reload” to get this page to load properly)

The MD interviewed by GMA, Dr. Marie Savard, notes that it may be several years before we know if this treatment will be proven effective. This is still very early in the research into this drug. The GMA clip suggests people look on clinicaltrials.gov for trial info. I’m not sure why. The Duke-managed trial is listed but nothing else.

There is no published data on the Duke-managed human trial. There is published data on the mouse trial. You can find the abstract on pubmed.gov using PubMed ID# 18199809. (You can pay $10 to access the full journal article online.)

Allon Therapeutics, a Canadian company, is the manufacturer of AL-108. Here’s the company’s 7/30/08 press release on the AL-108 research:
http://www.allontherapeutics.com/ir_jul30_2008.html
You can also dig around on their website to find their ICAD ’08 presentation.

For an outside perspective, this Medscape Medical News article is worth reading:
http://www.medscape.com/viewarticle/578314
The article points out that the results of the “12-week, phase 2a, double-blind, placebo-controlled study to evaluate the safety and tolerability of AL-108…showed that the drug had a positive effect on memory that was durable at 16 weeks in subjects randomized to the high-dose group (15 mg twice daily). However, the trial missed its primary efficacy end point — a composite of cognitive memory scores from the memory components of 4 cognitive tests — but did show a trend toward efficacy at weeks 8 and 16.” An Alzheimer’s researcher at Mayo Rochester was asked to comment on the trial. He noted that “(phase) 2 trials are not powered to show efficacy”; rather, they are designed to show if a medication is safe and tolerated.

Robin

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)