Category Archives: MSA

New NIH Pamphlet on MSA (November 2014)

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Someone on the ShyDrager Yahoo!Group recently posted a link to the NIH pamphlet on MSA. Though the link is the same as before, the pamphlet itself has been updated. The date on the current pamphlet is November 2014. The first version of this pamphlet was written in 2009.

The main changes between the 2009 version and the 2014 version are in the diagnosis section and the research section. The diagnosis section has a new paragraph about a DaTscan, which is a kind of PET scan that assess dopamine transporter function in a specific part of the brain. The pamphlet notes that “this test cannot differentiate between MSA and Parkinson’s disease.” I wish the pamphlet had said that not everyone with MSA will have reduced function of this transporter in this specific area of the brain.

In the research section, there’s a discussion of alpha-synuclein research:

“Recent studies have demonstrated that the alpha-synuclein taken from brain tissue of patients with MSA is a potent inducer of alpha-synuclein clumping when injected into the brain of experimental animals. … Research in animal models may determine if drugs that reduce the abnormal alpha-synuclein accumulation might be promising treatments for MSA.”

There’s also a note in the research section about the failed rifampicin trial. And the comment that “MSA is one of the diseases being studied as part of the NINDS Parkinson’s Disease Biomarkers Program.”

There’s a small change in the treatment section. The pamphlet notes that the FDA approved the medication droxidopa in 2014.

Here’s a link to the pamphlet:

www.ninds.nih.gov/disorders/msa/multiple_system_atrophy_pamphlet.pdf

Multiple System Atrophy
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service, National Institutes of Health
November 2014
NIH Publication No. 15-5597

Robin

“Atypical multiple system atrophy is a new subtype of frontotemporal lobar degeneration”

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This is an interesting paper out of the Mayo Clinic Jacksonville about “four patients…with clinical features consistent with frontotemporal dementia (FTD), including two with corticobasal syndrome, one with progressive non-fluent aphasia, and one with behavioral variant FTD.  None had autonomic dysfunction.”

Curiously, these four patients met the pathological criteria for multiple system atrophy (MSA).  These were all atypical MSA cases because “[all] had frontotemporal atrophy and severe limbic α-synuclein neuronal pathology.”

The Mayo researchers note a previous case report of a woman with progressive dementia, psychosis, and muscular rigidity “with neuropathological features of both MSA and LBD” (Lewy body dementia).  This could be a fifth case of atypical MSA with features of FTD.

Researchers also note that six other atypical MSA cases have been reported around the world.

They conclude:

“Atypical MSA does not fit into any of the current categories [of FTLD – frontotemporal lobar degeneration]. We propose a new category of FTLD for atypical MSA—FTLD-synuclein. Alternatively, atypical MSA could be considered a subtype of MSA in addition to MSA-P and MSA-C, namely MSA-FTD. From a clinical perspective, this is a more challenging diagnosis, since none of our patients carried an antemortem diagnosis of MSA; rather, the clinical picture was that of FTD.”

The abstract is copied below.

The things you learn via brain donation!

Robin

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Acta Neuropathologica. 2015 Jul;130(1):93-105. Epub 2015 May 12.

Atypical multiple system atrophy is a new subtype of frontotemporal lobar degeneration: frontotemporal lobar degeneration associated with α-synuclein.

Aoki N, Boyer PJ, Lund C, Lin WL, Koga S, Ross OA, Weiner M, Lipton A, Powers JM, White CL 3rd, Dickson DW.

Abstract
Multiple system atrophy (MSA) is a sporadic neurodegenerative disease clinically characterized by cerebellar signs, parkinsonism, and autonomic dysfunction. Pathologically, MSA is an α-synucleinopathy affecting striatonigral and olivopontocerebellar systems, while neocortical and limbic involvement is usually minimal. In this study, we describe four patients with atypical MSA with clinical features consistent with frontotemporal dementia (FTD), including two with corticobasal syndrome, one with progressive non-fluent aphasia, and one with behavioral variant FTD. None had autonomic dysfunction. All had frontotemporal atrophy and severe limbic α-synuclein neuronal pathology. The neuronal inclusions were heterogeneous, but included Pick body-like inclusions. The latter were strongly associated with neuronal loss in the hippocampus and amygdala. Unlike typical Pick bodies, the neuronal inclusions were positive on Gallyas silver stain and negative on tau immunohistochemistry. In comparison to 34 typical MSA cases, atypical MSA had significantly more neuronal inclusions in anteromedial temporal lobe and limbic structures. While uncommon, our findings suggest that MSA may present clinically and pathologically as a frontotemporal lobar degeneration (FTLD). We suggest that this may represent a novel subtype of FTLD associated with α-synuclein (FTLD-synuclein).

PMID: 25962793  (see pubmed.gov for the abstract only)

Pain more severe and common in PD and MSA compared to PSP

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In this small study, these patient populations were compared — 21 with multiple system atrophy (MSA), 16 with progressive supranuclear palsy (PSP), and 65 with Parkinson’s Disease (PD).  Europeans researchers showed that pain was “significantly more common and more severe in PD and MSA compared to PSP.”

The full abstract is copied below.

Robin

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Brain & Behavior. 2015 May;5(5):e00320. Epub 2015 Mar 25.

Pain in multiple system atrophy and progressive supranuclear palsy compared to Parkinson’s disease.

Kass-Iliyya L, Kobylecki C, McDonald KR, Gerhard A, Silverdale MA.

Abstract
BACKGROUND:
Pain is a common nonmotor symptom in Parkinson’s disease (PD). The pathophysiology of pain in PD is not well understood. Pain characteristics have rarely been studied in atypical parkinsonian disorders such as Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP).

AIM OF THE STUDY:
We aimed to evaluate pain intensity, location, and associated symptoms in atypical parkinsonian disorders compared to PD.

METHODS:
Twenty-one patients with MSA, 16 patients with PSP, and 65 patients with PD were screened for pain using question 1.9 of the MDS-UPDRS. Pain intensity was quantified using the short form McGill Pain Questionnaire (SFMPQ). Pain locations were documented. Motor disability was measured using UPDRS-III. Affective symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS).

RESULTS:
Pain was significantly more common and more severe in PD and MSA compared to PSP (P < 0.01). Pain locations were similar with limb pain being the most common followed by neck and back pain. Pain intensity correlated with HADS scores but not motor severity.

CONCLUSIONS:
Pain is more common and more intense in PD and MSA than PSP. Differences in distribution of neurodegenerative pathologies may underlie these differential pain profiles.

PMID: 25874161

Guide on how to diagnose MSA, etc. (Neurologic Clinics, Feb. 2015)

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I ran across an interesting medical journal article today that provides a guide for neurologists on how to diagnose three atypical parkinsonism disorders — PSP (progressive supranuclear palsy), CBD (corticobasal degeneration), and MSA (multiple system atrophy.

The full article is available online for a fee.  See:

www.neurologic.theclinics.com/article/S0733-8619(14)00080-2/fulltext

“Atypical Parkinsonism: Diagnosis and Treatment”
Maria Stamelou, MD, PhD and Kailash P. Bhatia, FRCP
Neurologic Clinics 33 (2015) 39-56

Here’s a short overview of MSA from the article:

“MSA is a neurodegenerative disorder characterized by autonomic failure and parkinsonism and/or cerebellar signs. MSA-parkinsonism (MSA-P) is characterized predominantly by parkinsonism and autonomic failure at presentation, whereas in MSA-cerebellar type (MSA-C), cerebellar signs occur with autonomic failure. However, during disease progression, cerebellar signs often develop in patients with MSA-P and parkinsonism in MSA-C. The prevalence is about 4 per 100,000. Typical age at onset is 53 to 55 and onset before age 30 has never been reported. Men and women are equally affected, and mean survival time is 9 years from symptom onset.”

The authors ask the question – why is it so hard to diagnose these atypical parkinsonian disorders accurately during life?  Their answers:

“[The] early differential diagnosis is complicated by patients with pathologically proven PSP, CBD, or MSA that may present clinically with phenotypes other than the classic ones.  Conversely, patients with the classic AP [atypical parkinsonism] phenotypes may turn out to have other pathologic abnormalities.” 

So, basically, it’s really hard to tell all of these disorders apart.

The authors ask:  “if it’s not PSP, CBD, or MSA, what could it be?”  One disorder it could be is Parkinson’s Disease (PD).  What else could it be if it’s not PD?  Very commonly, it’s one of the other atypical parkinsonian disorders — PSP, CBD, MSA, and DLB (Dementia with Lewy Bodies).

What else could it be if it’s not one of the other atypical parkinsonism disorders?  For MSA, it’s vascular parkinsonism or primary progressive MS (multiple sclerosis).

I recommend shelling out some money on this article.

Robin

Webinar on alpha-synuclein and Lewy bodies

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Tomorrow’s Michael J. Fox Foundation “Third Thursday Webinar” may be of interest to you.  It’s from 9am to 10am California time.  The topic is alpha-synuclein protein.  This is the protein involved in Parkinson’s Disease (PD), Multiple System Atrophy (MSA), and Lewy Body Dementia (LBD).  (A different protein is involved with PSP and CBD.)  The webinar will look at research underway to determine if the aggregation of this protein causes diseases and to stop alpha-synuclein from clumping in the brain.

We all have alpha-synuclein protein in our brains.  In PD, the amount of alpha-synuclein in the brain is two or three times the normal amount.

We will also hear the term “Lewy body” on tomorrow’s webinar.  Lewy bodies are the clumps of alpha-synuclein protein that appear in PD and LBD.  Lewy bodies are NOT part of MSA.

If you can’t make the webinar tomorrow due to the time it’s being held but you are interested in the topic, I encourage you to register for the webinar.  Those who register will receive an automatic email indicating when the recording of the webinar is available online.

To find a “Register Now” button and for information on the webinar series, see:
michaeljfox.org/webinars

Robin