Pregnancy is associated with faster disease progression (MSA)

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This is a case report by Washington University (St. Louis) clinicians of a 31-year-old Irish woman who lived in the midwest US with parkinsonism, initially diagnosed with Parkinson’s Disease.  She had a baby at age 35.  “Her pregnancy was complicated by severe orthostatic hypotension and motor fluctuations.”  At age 37, she had DBS (deep brain stimulation).  She died eight years after disease onset.  Upon brain autopsy, it was found she had multiple system atrophy (MSA).  The authors conclude that “pregnancy may be associated with marked disease progression.”

I don’t know if the authors considered that the DBS may’ve been associated with “marked disease progression.”  If anyone looks, let me know!

I’ve copied the abstract below.  The full article is available at no charge online.

Also, this must be one of the youngest documentated cases of MSA.

Robin

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www.jmedicalcasereports.com/content/pdf/1752-1947-5-599.pdf  –> full article is available here at no charge

Journal of Medical Case Reports. 2011 Dec 30;5(1):599. [Epub ahead of print]

Pregnancy in multiple system atrophy: a case report.

Zhu L, Cairns NJ, Tabbal SD, Racette BA.

Abstract
INTRODUCTION:
Multiple system atrophy is a late, adult-onset alpha-synucleinopathy with no data on the effect of pregnancy on the disease course. Early stage multiple system atrophy can be difficult to distinguish from Parkinson’s disease.

CASE PRESENTATION:
We describe the case of an Irish woman with parkinsonism starting at age 31, initially diagnosed as having dopa-responsive, idiopathic Parkinson’s disease, who successfully delivered a full-term child at age 35. Her pregnancy was complicated by severe orthostatic hypotension and motor fluctuations. Two years post-partum, she underwent bilateral subthalamic nuclei deep brain stimulation for intractable motor fluctuations and disabling dyskinesia. After this treatment course she experienced deterioration of motor symptoms and death eight years after disease onset. Post-mortem neuropathological examination revealed striatonigral degeneration and alpha-synuclein-positive glial cytoplasmic inclusions in brain stem nuclei, basal ganglia and white matter tracts, consistent with a neuropathological diagnosis of multiple system atrophy.

CONCLUSIONS:
Multiple system atrophy can affect women of child-bearing age and pregnancy may be associated with marked disease progression.

PubMed ID#: 22208291  (see pubmed.gov for the abstract only)

Four Markers of Future Neurological Problems

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This Italian paper notes that many people develop RBD (REM sleep behavior disorder) and, on average, 25 years later many of them develop a neurological disorder, such as Lewy body dementia (LBD), Parkinson’s Disease (PD), or multiple system atrophy (MSA).  Authors say:

“The estimated 10-year risk of neurodegenerative disease for…RBD is about 40%.” 

Obviously, it would be good to identify who is in that 40% bucket.  The authors indicate that potential markers of neurodegeneration include:

(1) marked EEG slowing on spectral analysis;
(2) decreased striatal 123I-FP-CIT binding and substantia nigra hyperechogenicity;
(3) impaired olfactory function;
(4) impaired color vision.

I was in a meeting once with a neurologist and a local support group member.  The neurologist was reviewing the late husband’s neuropathology report.  I remember the neurologist being very interested in finding the EEGs done on the husband early on as he said that a certain finding on an EEG would’ve been an indicator the husband was going to develop a neurological disorder.”

This is the first time I’ve seen “impaired color vision” as a potential marker.

I’ve copied the abstract of the medical journal article below.

Robin

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Sleep Medicine. 2011 Dec;12 Suppl 2:S43-9.

Does idiopathic REM sleep behavior disorder (iRBD) really exist? What are the potential markers of neurodegeneration in iRBD?

Ferini-Strambi L.
Sleep Disorders Center, Vita-Salute San Raffaele University, Milan, Italy.

Abstract
REM sleep behavior disorder (RBD) may be idiopathic or associated with other neurologic disorders. A strong association between RBD and a-synucleinopathies has recently been observed, with the parasomnia often heralding the clinical onset of the neurodegenerative disease. The idiopathic form accounts for up to 60% of the cases reported in the three largest series of patients with RBD. Some clinical follow-up studies revealed that a large proportion of these patients will eventually develop a parkinsonian syndrome or a dementia of the Lewy bodies type in the years following the RBD diagnosis. The estimated 10-year risk of neurodegenerative disease for idiopathic RBD is about 40%. Moreover, it has been reported that the median interval between RBD and subsequent neurologic syndrome is 25years. Several studies have looked at neurophysiologic and neuropsychological functions in idiopathic RBD and have found evidence of CNS dysfunction during both wakefulness and sleep in a variable proportion of these patients, challenging the concept of idiopathic RBD. Identifying subjects with a high risk of developing a neurodegenerative process may be crucial to develop early intervention strategies. Prospective studies in idiopathic RBD showed that potential markers of neurodegeneration include: (1) marked EEG slowing on spectral analysis; (2) decreased striatal 123I-FP-CIT binding and substantia nigra hyperechogenicity; (3) impaired olfactory function; (4) impaired color vision.

PubMed ID#: 22136899  (see pubmed.gov for this abstract only)

 

Test cannot differentiate PD and MSA early-on

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This is an interesting Swedish study.  As you may know, a test that examines how well the anal sphincter works is a good test to differentiate Parkinson’s Disease from multiple system atrophy (MSA).  According to the abstract of this article, that test only differentiates PD and MSA “many years into the disease.”

In the Swedish study, they examined 148 newly-diagnosed patients — 100 definite PD, 21 probable PD, 16 MSA, 11 progressive supranuclear palsy, and 40 controls.  They gave them all an external anal sphincter electromyography (EAS-EMG) within 3 months of their first visit.  They found:  “No EAS-EMG differences were found between the patient groups, especially not between PD and MSA.”  So they concluded that this test cannot differentiate PD and MSA early in the disease course.

The abstract to the medical journal article is copied below.

Robin

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Acta Neurologica Scandinavica. 2012 Jan 3.  [Epub ahead of print]

Anal sphincter electromyography in patients with newly diagnosed idiopathic parkinsonism.

Linder J, Libelius R, Nordh E, Holmberg B, Stenlund H, Forsgren L.
Department of Pharmacology and Clinical Neuroscience, Epidemiology and Public Health Sciences, Umeå University, Umeå, Sweden.

Abstract
OBJECTIVES:
The differential diagnosis of patients with idiopathic parkinsonism is difficult, especially early in the course of the disease. External anal sphincter electromyography (EAS-EMG) has been reported to be of value in the differential diagnosis between Parkinson’s disease (PD) and multiple system atrophy (MSA). Patients with MSA are reported to have pathological EAS-EMG and patients with PD are reported to have significantly less pathological EAS-EMG results. Comparisons between patients with parkinsonian disorders have usually been made many years into the disease, and thus it is largely unknown if the results of EAS-EMG can be used to distinguish the different diagnoses in the early phase of the disease.

MATERIALS AND METHODS:
We investigated 148 newly diagnosed patients with idiopathic parkinsonism from a population-based incidence cohort (100 definite PD, 21 probable PD, 16 MSA, 11 progressive supranuclear palsy, and 40 controls) with EAS-EMG within 3 months of their first visit and, in the majority of patients, before start of treatment with dopaminergic drugs. The clinical diagnoses were made using established clinical diagnostic criteria after a median follow-up of 3 years.

RESULTS:
All patient groups had more pathological EAS-EMG results than controls. No EAS-EMG differences were found between the patient groups, especially not between PD and MSA.

CONCLUSIONS:
External anal sphincter electromyography examination cannot separate the different parkinsonian subgroups from each other in early course of the diseases.

© 2012 John Wiley & Sons A/S.

PubMed ID#: 22211900  (see pubmed.gov for this abstract only)

Delayed gastric emptying in MSA

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In this Japanese study, “gastric emptying” was studied in 25 patients with multiple system atrophy (MSA), 20 patients with ataxia, and 20 healthy volunteers.

The authors concluded:

“These results suggested that gastric emptying was significantly delayed in patients with MSA, and the delay already appeared in the early stage of the disease. Delayed gastric emptying is one of the autonomic failures and may be a clinical marker of MSA.”

Since these autonomic symptoms can also occur in Parkinson’s Disease and Lewy Body Dementia, I think a good follow-on study would be to see if delayed gastric emptying occurs any earlier in MSA than in other disorders.

The abstract to the article is copied below

Robin

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Journal of Neurology. 2012 Jan 5. [Epub ahead of print]

Is there delayed gastric emptying in patients with multiple system atrophy? An analysis using the (13)C-acetate breath test.

Tanaka Y, Kato T, Nishida H, Yamada M, Koumura A, Sakurai T, Hayashi Y, Kimura A, Hozumi I, Araki H, Murase M, Nagaki M, Moriwaki H, Inuzuka T.
Department of Neurology and Geriatrics, Graduate School of Medicine, Gifu University, Gifu City, Japan.

Abstract
Autonomic failure is one of the criteria according to the second consensus statement for the diagnosis of multiple system atrophy (MSA). Gastrointestinal symptoms are frequent complaints in patients with MSA and may be associated with reduced gastrointestinal motility due to autonomic nervous system dysfunction. However, there are few reports on gastric emptying in patients with MSA. We investigated gastric emptying in 25 patients with MSA, 20 patients with sporadic adult-onset ataxia of unknown etiology (SAOA), and 20 healthy volunteers using the (13)C-acetate breath test. Gastric emptying function is estimated by this test as the half-emptying time (HET) and peak time of the (13)C-%-dose-excess curve (T (max)), with expirations collected for 4 h after a test meal and determination of (13)CO(2) content using an infrared (IR) spectrophotometer. The HET and T (max) of gastric emptying were significantly delayed in patients with MSA as compared to those in SAOA and controls (p < 0.01). The HET and T (max) were not significantly different between SAOA and controls. No correlation existed between the HET or T (max) and the duration or severity of the disease in MSA patients. These results suggested that gastric emptying was significantly delayed in patients with MSA, and the delay already appeared in the early stage of the disease. Delayed gastric emptying is one of the autonomic failures and may be a clinical marker of MSA.

PubMed ID#: 22218651   (see pubmed.gov for this abstract only)

 

Explaining “high,” “intermediate,” and “low” chances of DLB

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One of Brain Support Network’s mission is to help families with brain donation arrangements.  We’ve seen lots of neuropathology reports come back with various descriptions of “Lewy body disease” and the cover letters indicate the person had “Lewy body dementia.”  Within the “comments” section of the reports terms such as “low,” “intermediate,” and “high” are used.  This post attempts to explain that terminology.

Most of the neuropathology reports I read are from the Mayo Clinic in Jacksonville.  The neuropathologist there, Dr. Dennis Dickson, is one of the top in the world.  He co-authored the diagnostic criteria for Dementia with Lewy Bodies.  That criteria can be found in this important paper:

Neurology. 2005 Dec 27;65(12):1863-72.
Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium.
McKeith IG, many others, and Consortium on DLB.

Interestingly, neuropathologists don’t say that someone had Lewy Body Dementia (or Dementia with Lewy Bodies) as that’s a clinical diagnosis, not a neuropathologic one.  They may say something like “based on the clinical picture, the level of Lewy bodies, and the level of Alzheimer’s pathology, the LIKELIHOOD this donor had Dementia with Lewy Bodies is high/intermediate/low.”

There’s a chart in the McKeith paper that neuropathologists rely on in making this statement. The table is titled “Assessment of the likelihood that the pathologic findings are associated with a DLB clinical syndrome.”  On one axis is “Lewy body type pathology,” where the choices are Brainstem, Limbic (transitional), and Diffuse neocortical.  On the other axis is “Alzheimer’s type pathology,” where the choices are NIA-Reagan Low (Braak stage 0-2), NIA-Reagan Intermediate (Braak stage 3-4), and NIA-Reagan High (Braak stage 5-6).

If the Lewy body pathology is Limbic or Diffuse and the amount of Alzheimer’s pathology in the brain is low, the “likelihood that the pathologic findings are associated with a DLB clinical syndrome” are “high.” Conversely, if the LB pathology is Brainstem or Limbic and the amount of Alzheimer’s pathology in the brain is high, the “likelihood that the pathologic findings are associated with a DLB clinical syndrome” are “low.”

Here’s a related post about the severity of Lewy bodies in the brain that explains brainstem, limbic (transitional), and diffuse.

Typically, Lewy Body pathology and Alzheimer’s pathology co-occur in the brain of someone with Lewy body dementia.  In my layperson’s mind, the low-intermediate-high language is basically a gauge to say which pathology is more important in terms of overall pathologies found in the brain — is it Lewy Body pathology or Alzheimer’s pathology?

Let me know if you have questions!

Robin