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Human cytomegalovirus infection in post left middle cerebral artery ischemic stroke patients A R esearch P roposal 5-23-2013 Resident: John Ma, MD & PhD, PGY-2 Mentors: Jay Hammock, MD & Erika Erlandson , MD Department of Physical Medicine & Rehabilitation
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Human cytomegalovirus infection in post left middle cerebral artery ischemic stroke patients
A Research Proposal
Resident: John Ma, MD & PhD, PGY-2
Mentors: Jay Hammock, MD & Erika Erlandson, MD
Department of Physical Medicine & Rehabilitation
University of Kentucky School of Medicine
HCMV is a member of the viral family Herpesviridae. Itis also known as human herpesvirus-5 (HHV-5). It is a DNA virus, infects humans in early in childhood transmitted by saliva, urine in daycare settings. After viremia, some individuals clear the viral infection; however, most of us experience latent infection throughout life. Like HSV, HCMV re-emerges when the host becomes immunocompromised.
infects lung, liver, spleen, kidney, glands, bladder, bone marrow, CNS etc.
Latent infection, (months, years, life long)
Immunocompromised or decreasing immunity level
such as HIV infection, immunosuppression, pregnancy, newborn, leukemia etc.
CMV reactive infection
In immunocompetent people:
No symptoms or flu like symptoms such as fatigue, malaise, runny nose, sore throat, low grade fever, muscle ache, or adenopathy
In immunocompromised people:
- Visual impairment and blindness
- Ulcers of the digestive tract, possibly causing bleeding
- Inflammation of the brain (encephalitis)
- Behavioral changes
Cannon et al, Rev med virol, 2012, 20, 202-213
1. Chronic CMV infection is a risk factor of ischemic stroke, [Kis et al, New Microbiolgica, 2007, 30, 213-220] , [Huang et al, CNS Neuroscice & Therapeutic, 2012, 18, 457-460]
2. CMV and HSV infection are risk factors for future myocardial infarction and stroke [Ridker et al, Circulation , 1998, 98, 2796-2799]
3. Significantly higher rate of cognitive decline with high levels of anti-CMV[Aiello et al, J. Am Geriatr Soc, 2006, 54, 1046-1054]
4. Chronic CMV infection is associated with ADLs impairment [Aiello et al, J. Gerontol. A BiolSci Med Sci, 2008, 63(6), 610-618]
5. Chronic CMV infection is associated with prevalent frailty [Schmaltz et al, J. Am Geriatr Soc, 2005, 53, 747-754]
Lt MCA ischemic Stroke
Stress to immune system
Latent HCMVs become active
Subclinical/clinical symptoms such as fatigue, low grade fever, malaise,
cognitive impairment, frailty and impairment on ADLs
Poor endurance, less motivated to anticipate in rehab program
Taking more time to reach maximal rehab goal
Prolonged rehab hospital stay and increased Medicare/Medicaid expense
1. New onset 1st time Left MCA ischemic infarct at age 60-70
2. Cognitively being able to participate in rehab
3. Willing to participate in the research study
Known immunosuppression (e.g., organ transplants)
Known HIV infection
Known active PNA or UTI
Known long term use of steroid hormones
Recent major surgery peri-stroke or post-OP stroke
End-stage renal, liver, and/or lung disease
Recurrent and/or chronic stroke
Cancer patients with recent chemotherapy and/or XRT
Very sick patients unable to participate rehab program
Severe dementia/end stage of Alzheimer’s disease
Age, gender, left MCA stroke (closed size) , similar co-morbidities such as
DM, HTN, HLD, CKD, CAD, COPD, social-economic status, BMI matched
HCMV IgG in serum (ELISA)
HCMV IgG (-) HCMV IgG (+)
qPCR (-) qPCR (+)
Comparison of FIM, PT/OT/SLP and hospital stay
ELISA: enzyme-linked immunosorbentassasy
qPCR: quantitative polymerase chain reaction
Group Initial & d/c FIM ∆ FIM ∆ PT/OT/SLP Rehab days
HCMV IgG (-) /☻ ☻☻fair/well
HCMV IgG (+), qPCR (-) /☺ ☺☺ fair/delay
HCMV IgG (+), qPCR (+) / longer .
Possible relationship between FIM PT/OT/SLP performance and HCMV titer:
0 10 100 1,000 10,000 100,000
Viral copies by quantitative PCR
If our hypothesis is true that active CMV delays pts’ discharge, then we will further explore whether treatment of HCMV will improve rehab performance and/or decrease their hospital stay.
If our hypothesis is confirmed to be true, then a similar study design can be applied to TBI, SCI, and GRU patients.
Prevalence and effects of other chronic infections such as HSV, EBV and H. Pylori etc. can be evaluated in a rehab hospital setting.
Dr. Jay Hammock
Constant encouragement and help from:
Dr. Nickerson, Dr. Schleenbacker, Dr. Ortiz,
Dr. Stiles and Dr. Erlandson
Enthusiastic comments on the proposal from:
Dr. Sawaki and Dr. Springer
The GREATEST study partners & friends :
All the residents in this program, especially Dr. Thien Ngo
and Dr. Dwan Perry.