Category Archives: MSA

New book by Parkinson’s Plus Patient Dan Brooks

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Dan Brooks started a blog about his life with Parkinson’s Plus in December 2006. (Ru posted about this on The Back Porch.) The blog — at http://wewillgoon.blogspot.com/ — has grown into a book, which has just been published! The book, “I Will Go On: Living with a Movement Disorder,” is available online through Amazon* for $16. Here’s some info from amazon.com about the book:

“Dan was a 50-year-old husband, father and district-level administrator in a public school system, when he first noticed pronounced tremors, speech difficulties and walking problems developing. In this book, Daniel chronicles his life with a Parkinson’s Plus syndrome and explains how he dealt with the neurological decline that resulted. Read a user-friendly, patient’s explanation of the defining symptoms of these atypical Parkinsonism disorders and find out how this neurodegenerative disease progressed in Dan’s case. This book addresses the many facets of neurodegenerative diseases, while primarily focusing on Atypical Parkinsonian disorders, namely PSP, MSA, and CBD. Parkinson’s Disease is also discussed in depth. Dan tells a compelling and inspirational story of how he maintained his faith in God, while courageously facing life with a movement disorder.”

Dan’s goal is to encourage and inspire patients or caregivers as they face the challenges posed by neurodegenerative illness. He wrote to me: “Sometimes this medical condition is overwhelming, as you know, but I have adjusted and learned to accept what is happening. There is still a lot of life to live and I am very energized right now by this book project. … I am very pleased to have finished [the book]. My hope is that patients and caregivers will appreciate the patient’s viewpoint from which I write. … If I help one person with this book, it will have been worth the effort.”

You can read an overview about the book and learn more about Dan at his blog http://wewillgoon.blogspot.com/ I’m sure you will agree that he’s a remarkable person! Many of us count ourselves lucky that our paths have crossed with his.

Robin

* Link to amazon.com for “I Will Go On: Living with a Movement Disorder”
http://www.amazon.com/Will-Go-Living-Mo … 597&sr=8-1

Can olfactory bulb biopsy distinguish PSP – MSA – PD?

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The last line of this abstract caught my eye: “It is suggested that olfactory bulb biopsy be considered to confirm the diagnosis in PD subjects being assessed for surgical therapy.” In the article, the authors indicate that one of their concerns is that MSAers, misdiagnosed as having PD, will get deep brain stimulation and will be harmed by that. They say:

“It has been reported that patients with multiple system atrophy (MSA) misdiagnosed as PD have undergone placement of deep brain stimulators and have not had a lasting benefit. As the characteristic glial cytoplasmic synuclein-immunoreactive inclusions of MSA are also present and diagnostic in the olfactory bulb, as reported by Kovacs et al. (we have confirmed this finding in five MSA cases), olfactory bulb biopsy would differentiate between PD and MSA. Olfactory bulb biopsy might therefore be useful for the evaluation of candidates for surgical therapy of PD, where the risks of biopsy might be justified if it would spare non-PD subjects the greater risks associated with pallidotomy, thalamotomy, deep brain stimulation or neural transplantation.”

In one of the response letters, scientists asked specifically about PSP and MSA. The authors of the main article reply:

“The authors question whether olfactory bulb biopsy could distinguish PD from MSA or PSP, especially since Lewy bodies may be present in sparse numbers in both of the latter two conditions. We have utilized olfactory bulb alpha-synuclein stains in six MSA cases, and found all had numerous and characteristic flame-shaped glial cytoplasmic inclusions, unambiguously identifying these as MSA. It may be more difficult to distinguish PD from PSP. Our data show that 15 of 45 PSP cases had olfactory bulb Lewy bodies. Of these 15, the majority also had Lewy bodies in the brainstem and limbic region, suggesting that these subjects had both PD and PSP. Whether or not these subjects would differ in surgical outcome from those with pure PD or pure PSP is not known at this time. We are currently testing methods for detecting glial tauopathy to determine whether these might positively identify PSP subjects from olfactory bulb material.”

So an olfactory bulb biopsy — which is a relatively minor surgical procedure done while someone is alive — would differentiate PD from MSA but not PD from PSP. To increase the success rate of deep brain stimulation going forward, it sounds like researchers may require an olfactory bulb biopsy to weed out the MSAers.

And I thought the part about “testing methods for detecting glial tauopathy to determine whether these might positively identify PSP subjects from olfactory bulb material” was interesting too.

Probably not many of you will want to read the abstract (or the full paper). But if you do and you pick up a different facet, please share!

Robin

Acta Neuropatholpgica. 2009 Feb;117(2):169-74. Epub 2008 Nov 4.

Olfactory bulb alpha-synucleinopathy has high specificity and sensitivity for Lewy body disorders.

Beach TG, White CL 3rd, Hladik CL, Sabbagh MN, Connor DJ, Shill HA, Sue LI, Sasse J, Bachalakuri J, Henry-Watson J, Akiyama H, Adler CH; Arizona Parkinson’s Disease Consortium.
Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ.

Involvement of the olfactory bulb by Lewy-type alpha-synucleinopathy (LTS) is known to occur at an early stage of Parkinson’s disease (PD) and Lewy body disorders and is therefore of potential usefulness diagnostically. An accurate estimate of the specificity and sensitivity of this change has not previously been available. We performed immunohistochemical alpha-synuclein staining of the olfactory bulb in 328 deceased individuals. All cases had received an initial neuropathological examination that included alpha-synuclein immunohistochemical staining on sections from brainstem, limbic and neocortical regions, but excluded olfactory bulb. These cases had been classified based on their clinical characteristics and brain regional distribution and density of LTS, as PD, dementia with Lewy bodies (DLB), Alzheimer’s disease with LTS (ADLS), Alzheimer’s disease without LTS (ADNLS), incidental Lewy body disease (ILBD) and elderly control subjects. The numbers of cases found to be positive and negative, respectively, for olfactory bulb LTS were: PD 55/3; DLB 34/1; ADLS 37/5; ADNLS 19/84; ILBD 14/7; elderly control subjects 5/64. The sensitivities and specificities were, respectively: 95 and 91% for PD versus elderly control; 97 and 91% for DLB versus elderly control; 88 and 91% for ADLS versus elderly control; 88 and 81% for ADLS versus ADNLS; 67 and 91% for ILBD versus elderly control. Olfactory bulb synucleinopathy density scores correlated significantly with synucleinopathy scores in all other brain regions (Spearman R values between 0.46 and 0.78) as well as with scores on the Mini-Mental State Examination and Part 3 of the Unified Parkinson’s Disease Rating Scale (Spearman R -0.27, 0.35, respectively). It is concluded that olfactory bulb LTS accurately predicts the presence of LTS in other brain regions. It is suggested that olfactory bulb biopsy be considered to confirm the diagnosis in PD subjects being assessed for surgical therapy.

PubMed ID#: 18982334

The comments are:

Acta Neuropathologica. 2009 Feb;117(2):213-4; author reply 217-8. Epub 2008 Nov 25.
Can olfactory bulb biopsy be justified for the diagnosis of Parkinson’s disease?
Parkkinen L, Silveira-Moriyama L, Holton JL, Lees AJ, Revesz T.
Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
PubMed ID#: 19031077

Acta Neuropathologica. 2009 Feb;117(2):215-6; author reply 217-8. Epub 2008 Nov 5.
Olfactory bulb alpha-synucleinopathy has high specificity and sensitivity for Lewy body disorders.
Jellinger KA.
Institute of Clinical Neurobiology, Vienna, Austria.
PubMed ID#: 18985364

PSP/CBD Update – Diagnosis, Genetics, Treatment (Litvan ’07)

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Larry in southern California (whose wife has PSP) emailed several of the Yahoo!Groups yesterday about this August ’07 Irene Litvan article, asking if anyone knew anything about “transcranial sonography (TCS),” which is a diagnostic method mentioned in the article. Turns out that only a short paragraph of the Litvan article was on TCS. Dr. Irene Litvan is one of the top experts in the world on PSP. She’s written quite a bit on CBD and MSA as well.

This review article is an update for neurologists as to what advancements have been made in the area of diagnostic tools, genetics, and treatments for PSP, CBD, and MSA. The rest of this post is a summary of what I learned from the article. If you want more details, read the abstracts of the articles on PubMed (pubmed.gov – enter in the ID#). (A few of the full articles are available online for free. It’s mostly the harder-to-comprehend papers that are free!)

Dr. Litvan, writing in August ’07, concludes the article by saying that the field of atypical Parkinsonian disorders — diagnostic tools, genetics, and treatment — has “significantly advanced over the past year.” From a patient/family perspective, it is hard to agree with her.

DIAGNOSIS. From the article, I learned about recent studies of four diagnostic methods using “ancillary tools”:

1. TCS (transcranial sonography): TCS may help distinguish PD vs. atypicals, PD vs. MSA/PSP, MSA/PSP vs. CBD, and perhaps PSP vs. CBD, if I’m reading this correctly. PSP can be differentiated from CBD because the dilation of the third ventricule of the brain has so far only been described in PSP. This TCS study was done in Europe. TCS cannot be performed in up to 20% of patients. The study had nothing to say about LBD or about differentiating MSA from PSP. Of all the papers referenced in her review article, this is the only one labeled as “of outstanding interest” by Dr. Litvan. (PubMed ID#17189043)

2. Diffusion-weighted MRI: This method may help distinguish PSP and MSA-P. (PubMed ID#17089396)

3. T2-weighted MRI: This method may help differentiate MSA and PD. (PubMed ID#17361340)

4. Saccade tasks: This sort of diagnostic test (of saccade latencies and directional errors) would be performed by a neuro-ophthalmologist. This test may help distinguish PSP vs. CBD/PD. (PubMed ID#17124191)

GENETICS. From the article, I learned some things about genetics that I was unaware of:

* The location of a second genetic risk for PSP was identified in 2007. (This utilized brain tissue at the Mayo Jax PSP Brain Bank. PubMed ID#17357082; very challenging reading)

* The LRRK2 genetic mutation, which can be a factor in PD and DLB, is “not associated with MSA or with sporadic PSP.” (This is the genetic mutation that was discussed in the Frontline program last week on PD, “My Father, My Brother, and Me.”)

TREATMENT. And here’s what I learned about treatment:

* Because of the success (“significant gait and postural balance benefits”) of an Italian study of DBS in two locations of the brain in advanced PD patients, Dr. Litvan believes that DBS of the pedunculopontine nucleus (PPN) “may be useful in treating the balance and gait disorder in the atypical parkinsonian disorders, particularly in patients with PSP and MSA.” In fact, CurePSP is funding a study of DBS of the PPN in those with PSP in Toronto. (PubMed ID#17251240)

* Mayo Rochester is studying respiratory dysfunction in MSA. (PubMed ID#17235127; very challenging reading)

* Transgenic mice models are being developed for PSP, CBD, and MSA.

What follows are the abstract of the article.

Robin

Current Opinion in Neurology. 2007 Aug;20(4):434-7.

Update of atypical Parkinsonian disorders.

Litvan I.
Department of Neurology, University of Louisville, Louisville, Kentucky.

PURPOSE OF REVIEW: This timely update discusses novel diagnostic approaches, recently identified genes, and innovative experimental symptomatic treatments for these devastating disorders.

RECENT FINDINGS: Differential patterns in the basal ganglia transcranial sonography, magnetic resonance diffusion-weighted imaging regional apparent diffusion coefficients in the brainstem, basal ganglia T2-weighted gradient echo sequences combined with fluid attenuated inversion recovery, or saccades error rates in single and mixed-task blocks could help differentiate the various parkinsonian disorders. In addition to the familial tauopathies (frontotemporal dementia associated with chromosome 17) presenting with an atypical parkinsonian phenotype, ‘TDP-43opathies’ and ‘tataboxbinding or ataxinopathies’, depending on the protein deposited in the brain, widen the scope of the familial atypical parkinsonian disorders. Recent identification of novel deep brain stimulation targets such as the pedunculopontine nucleus may help treat the balance and gait disorder in atypical parkinsonian disorders in the near future.

SUMMARY: These new findings are important for diagnosis, help better understanding of the nosology of these disorders, and will likely in the near future impact our clinical practice.

PubMed ID#: 17620879 (see pubmed.gov for abstract only)

Bak article on cognitive profiles – AD, PSP, CBD, MSA, DLB

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Thomas Bak from the UK wrote a great article in Nov/Dec ’06 providing the cognitive profiles of those with AD, PSP, CBD, MSA, and DLB, based upon the subtests of ACE (Addenbrooke’s Cognitive Examination).

You can find it for free online here:
http://www.acnr.co.uk/NO06/ND06_review_cog.pdf

In that article, he says:

“There are two serious problems connected with the use of MMSE in this patient group [with parkinsonian syndromes]. Firstly, MMSE has been demonstrated to be particularly insensitive to frontal-executive dysfunction, which, as will be shown below, constitutes the most common cognitive deficit in basal ganglia diseases. Secondly, based on the unitary concept of dementia, it does not examine different cognitive domains but confines itself to one global ‘dementia score’. It is, therefore, unable to determine qualitative differences between diseases.”

He advocates the use of other tests besides or in addition to the MMSE. In particular, he likes Addenbrooke’s Cognitive Examination (ACE) test, which includes verbal fluency among other cognitive batteries. He says this test “has been validated in PSP, CBD
and MSA.”

Check out Figure 1 of his short, two-page article. Figure 1 shows the impairment levels of those with (clinical diagnoses of) AD, PSP, CBD, MSA, and DLB on the various ACE subtests of Orientation, Attention, Memory, Verbal Fluencies, Language, and Visuospatial functions.

I have referred to this article in other posts but I think it deserves it’s own topic!

“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.