Since 2004 the Shy Drager Syndrome/Multiple SystemAtrophy Support Group has funded an annual SDS/MSA Research Award to the most outstanding abstract submitted to the American Autonomic Society research meeting.
Priority will be given to work that will lead to an impact in patients’ lives. Honorees will receive a financial award of US$2,000. A lay summary of the work is required for distribution to the SDS patient community.
To apply for this award, send a message to Anita Zeller firstname.lastname@example.org
Prospective 5-year natural history study of probable multiple system atrophy (MSA) in 175 North American subjects
S. Gilman (1), P.A. Low (2), S. May (3), C. Tanner (4), M. Stern (5), P. Sandroni (2), S. Reich (6), F. Marshall (7), P. Novak (8), J. Jankovic (9), G. F. Wooten (10), B. Racette (11), D. Sletten (2), C. Shults (3)
(1) University of Michigan, Ann Arbor, MI; (2) Mayo Clinic, Rochester, MN; (3) University of California, San Diego, CA; (4) Parkinson’s Institute, Sunnyvale, CA; (5) University of Pennsylvania, Philadelphia, PA; (6) University of Maryland, Baltimore, MD; (7) University of Rochester, Rochester, NY; (8) Boston University, Boston, MA; (9) Baylor College of Medicine, Houston, TX; (10) University of Virginia, Charlottesville, VA; (11) Washington University, St. Louis, MO
This study, funded by NINDS, comprised a study of 11 North American sites and used standardized methodology and strict entry criteria for MSA. The study, led by Dr. Sid Gilman at University of Michigan, explored the natural history of MSA. We focused on patients who fulfill strict criteria for the disorder and asked the question of whether patients with different types of MSA have different outlooks. Patients with MSA most commonly have parkinsonism as the main feature (MSA-P). Some have ataxia (unsteadiness) and other symptoms of cerebellar involvement (MSA-C). We found that the most common first symptom was autonomic involvement. We also found that the outlook from the first symptom was very bad, with an average time to death a little over 5 years. The type of MSA did not result in any significant difference in prognosis, estimated as time to death (outlook). Symptoms of involvement of different domains of autonomic function were also not different between types. One take-home message of the study is that, in treatment trials, we need to identify early cases of the condition and try to stop the condition from progressing.
Quantitative analysis of dermal small fibers in Parkinson’s disease and multiple system atrophy
P. Novak (1), N. Bharat Marya (2), K. Whren (2), J. Bhawan (2)
(1) Autonomic Laboratory, Dept. Neurology, Boston University School of Medicine, Boston, MA, USA; (2) Dermatopathology Section, Dept. Dermatology, Boston University School of Medicine, Boston, MA, USA
Background: Skin biopsy provides information about the small fibers. Most reported studies have focused on analysis of the sensory epidermal fibers. In this study, we evaluated autonomic and sensory nerves in the dermis in patients with multiple system atrophy (MSA) or with Parkinson’s disease complicated by autonomic dysfunction (PD-A) using dermal sheet preparations (DSP). Methods: Skin biopsies from 5 PD patients complicated by autonomic dysfunction and 5 MSA patients were analyzed. The full-dermis thickness biopsy was performed with a 3 mm diameter punch. Samples were taken from the proximal and distal leg. DSP processing includes collagenase digestion, immunostaining with the nerve growth factor receptor p75 antibody and automatic fiber detection using phase symmetry image analysis applied on the horizontal views. Results: DSP visualizes small fibers with high contrast. Many fibers showed signs of degeneration including fragmentation, swelling, thinning and beading. The fiber density was reduced in PD-A patients (p<0.0001) compared to MSA patients. Conclusion: Digestion of skin samples by collagenase, staining with p75 antibody and use of horizontal views enables simultaneous visualization of large number of nerve fibers in dermis with high signal-to-noise ratio enabling automatic digital image analysis. Reduced small fiber density in PD-A patients suggests the presence of small fiber neuropathy in PD-A. DSP can aid in understanding the pathology of small fiber neuropathies, as with the distinction between PD and MSA.
Involvement of cardiovagal nuclei in MSA
A. M. Schmeichel (1), P. Sandroni (1), P. A. Low (1), J. E. Parisi (2), E. E. Benarroch (1) (1) Department of Neurology, Mayo Clinic, Rochester, MN, USA; (2) Department of Pathology, Mayo Clinic, Rochester, MN, USA
Experimental studies suggest that whereas the dorsal motor nucleus of the vagus (DMV) contributes to innervation of the heart, the ventrolateral portion of the NAmb (NAmbvl) is the primary source of cardiovagal innervation. Cardiovagal failure is a common finding in multiple system atrophy (MSA). We sought to determine whether there was a relationship between the degree of neuronal depletion in the DMV and NAvl and cardiovagal failure in MSA. Medulla was obtained at autopsy from 12 controls (7 men, 5 women, age 68±4 years) and 15 MSA cases (10 men, 5 women, age 63±2 years); postmortem delay was similar in both groups. All MSA patients had gastrointestinal manifestations; 5 had stridor; and 12 underwent autonomic testing showing orthostatic hypotension in all, cardiovagal failure in 8 and preserved cardiovagal responses in 4. There was no difference in disease duration between the MSA patients with or without cardiovagal failure. Sections were immunostained for choline acetyl transferase (CAT) to identify vagal cholinergic neurons. There was depletion of cholinergic neurons in MSA compared to controls both in the DMV (18±2 vs. 45±3 cells/section, respectively, p < 0.001) and the NAvl (4.6±05 vs. 10±0.5 cell/section, respectively, p < 0.001). In both nuclei, there was lower cell counts in patients with cardiovagal failure compared to those without cardiovagal failure; this was statistically significant in the NAvl (4.0±1 vs. 7.0±1 cell/section, p= 0.028). This was not the case in the DMV. These findings indicate that both the DMV and NAvl may contribute to cardiovagal failure in MSA, with perhaps a larger contribution from the Navl.
Differentiating between primary dysautonomias - multiple system atrophy, pure autonomic failure and Parkinson’s disease: a pathophysiology-based approach
Y Sharabi,1,2 B Eldadah,1 S Pechnik, 1 C Holmes,1 DS Goldstein1
1Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; 2Hypertension Unit, C. Sheba Medical Center, Tel Hashomer, Israel
Background: Parkinson’s disease (PD), pure autonomic failure (PAF) and multiple system atrophy (MSA) are three distinct neurodegenerative disorders yet difficult to distinguish. Recent mounting evidence suggests differences at the post ganglionic level. The aim of this study is to identify differences in functional and hemodynamic profile of these conditions, and differential responses to neuropharmacologic manipulations. Consequently we propose an algorithm to diagnose PD, PAF or MSA. Methods: A prospective comparative study was performed. 56 patients mean age of 62 ± 10.7 years, with autonomic failure and signs of neurodegenaration. All performed functional autonomic tests, plasma neurochemical analysis, 6-[18F]Fluorodopamine positron emission tomography (PET) scanning and Neuropharmacological testing. Results: PD patients showed resting tremor and L-dopa responsiveness, whereas slurred speech were more prevalent among MSA. None of the MSA patients reported of family history of neurodegeneration and none of the PAF reported of orthostatic tolerance. Resting HR was significantly lower among the PD patients. PAF patients had particularly low plasma levels of norepinephrine and epinephrine. All showed low relative increase in norepinephrine after standing. PET showed intact postsynaptic sympathetic cardiac innervation in MSA patients but absent in PD and PAF. BP changes to ganglion blockade or sympathetic activation were large in MSA compared to minimal change in PD or PAF. The PET and the neuropharmacologycal results are the two most distinctive characteristics between MSA and PD, and are strongly correlate with each other. Conclusions: MSA, PD and PAF can be differentiated based on simple clinical parameters: A discriminating scoring using: gender, resting tremor, L-Dopa responsiveness, slurred speech, family history for PD and heart rate at rest < 68 bpm.. Diagnostic confirmation can be achieved by focusing on the post-synaptic part of the autonomic nervous system either with F18 cardiac-radioactivity or BP response to trimetaphan and yohimbine.