PET Imaging Study of Neurochemical and Autonomic Disorders in Multiple System Atrophy (MSA)
Condition: Multiple System Atrophy - Parkinsonian Subtype (MSA-P); Multiple System Atrophy - Cerebellar Subtype (MSA-C)
MeSH terms: Multiple System Atrophy; Shy-Drager Syndrome; Autonomic Nervous System Diseases; Primary Dysautonomias; Atrophy
Study type: Observational

Summary: 
      Multiple system atrophy (MSA) is a disorder of the nervous system of unclear cause. In MSA
      there is degeneration (progressive loss) of nerve cells in several brain and spinal cord
      regions. The result is a variety of symptoms, from physical (parkinsonism, ataxia,
      incoordination, falls, slowness) to autonomic (fainting, bladder incontinence, sexual
      dysfunction) to sleep problems (dream enactment, sleep apnea).

      This research aims to help us better understand the patterns and timing of nerve degeneration
      relatively early in the disease, and how this affects symptoms and progression. For instance:

        1. Does MSA affect certain nerves that stimulate heart pumping? If so, does the severity of
           loss of heart nerves affect disease progression and survival?

        2. It is thought that MSA does not affect memory and thinking much, unlike other diseases
           (such as Parkinson's). Is this accurate? Is there loss of nerves that transmit
           acetylcholine (a neurochemical important in mental functioning)?

        3. What can we learn about mood and sleep in MSA, through visualizing the serotonin system
           in the brain? How does this relate to symptoms that subjects report in these often
           underappreciated areas?

      To answer these and other questions, investigators will take images of specific nerves in the
      brain and heart using Positron Emission Tomography (PET) scans. Such imaging gives us
      information that cannot be obtained from MRIs and CT scans. We will measure the levels of
      several nerve cell types: serotonin, acetylcholine, and norepinephrine. Subjects will also
      have many standardized assessments including quality-of-life and symptom assessments,
      neurological examination, autonomic assessments, neuropsychological assessments, coordination
      tests, and even assessments of vision and sense of smell. By pooling these results from many
      MSA patients, and comparing with other diseases (such as Parkinson's disease) we hope to gain
      a better understanding of what is happening early in MSA. Such knowledge could be very
      valuable in future efforts to develop better therapies in this rare disease.
    

Detailed description: 
      Positron Emission Tomography (PET) imaging involves injection of radioactive tracers (small
      amounts of biologically active molecules with radioactive atoms attached) and scanning the
      body to see where the tracers localize, and how intensely they "stick" there.

      The tracers are used in such small amounts that they do not affect brain or body functions.
      The amount of radioactivity used is also very small and disappears quickly. Overall radiation
      exposure for participants is low and well within accepted safety levels for the human body.
    

Observational model: Case-Only
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Possible or Probable Multiple System Atrophy of either Parkinsonian or Cerebellar sub-type
      
Biospecimen description: 
      DNA Banking (this is optional): Subjects will have whole blood drawn sample for DNA banking
      to support genetic research of human disease and human genetic factors. About two tablespoons
      (approximately 20 ml) of blood will be taken from you. The blood will be shipped to the
      laboratory of Dr. Philip Low, Mayo Clinic, MN. Dr. Low's laboratory will extract the DNA.
      Members of the North American MSA - Study Group and their collaborators will use the DNA to
      try to find out if changes in certain genes are associated with MSA. The samples will be used
      for the preparation of DNA, and possibly, an immortalized cell line. The cell line, DNA, and
      accompanying data will be distributed to scientists including those in research, teaching,
      and industry. The samples may be kept indefinitely. The samples and accompanying information
      will be used for studying of many disorders and genetic factors, not just MSA.
    
Keywords: MSA; Shy-Dragers Syndrome; Possible or Probable