Questions and Research Ideas
This page features some ideas for research.
- Pathogens in Children and Adolescents with ME/CFS:
Since viruses linked to ME/CFS, such as Epstein-Barr virus, have high rates of infection in adult population, studying infectivity rates in younger patients compared to age-matched controls might be more informative. A study like this was done for multiple sclerosis patients (Pohl 2006), which found "near-complete seropositivity for EBV antibody against virus capsid antigen" (98.6% in patients vs 72.1% in controls). That paper could be used as a model for a similar investigation of pediatric ME/CFS. It should be noted that VCA IgG responses do not develop in approximately 2% of EBV-infected individuals (De Paschale 2012).
Varicella-Zoster Virus (VZV) is the virus that causes chickenpox, with later reactivations causing shingles. Since the virus establishes latency in the autonomic and dorsal root ganglia, could it cause ME/CFS? The idea was raised in hypothesis paper (Shapiro 2009). As a vaccine for VZV became available in the 1990s, studying vaccinated persons to see if this changes the ME/CFS risk could help provide evidence to support or refute this hypothesis.
- Analysis of tissue vs. blood:
Efforts to find active EBV infection in blood of ME/CFS patients have led to negative or conflicting results. Analysis of tissues such as lymph nodes, tonsils, and fluids other than blood such as saliva and CSF might be more productive. A study of cervical lymph nodes from multiple sclerosis patients revealed a unique EBV signature (Sarkkinen 2025). Enlarged cervical lymph nodes have been reported in ME/CFS as far back as the London Royal Free Hospital outbreak in the 1950s and were a required aspect of the 1988 Holmes criteria and an optional part of the 1994 Fukuda and 2003 Canadian Consensus criteria. - Effect of anti-herpetics (e.g. valacyclovir/Valtrex, famciclovir/Favir) on risk of ME/CFS or Long COVID:
A study of persons taking valacyclovir (or related drugs) for HSV suppression to determine if this changes risk of Long COVID after COVID-19 illness, or ME/CFS generally. - Small Fiber Neuropathy:
Identification of small fiber neuropathy in a significant number of ME/CFS patients raises several questions. One technique for identifying SFN is through measuring intraepidermal nerve fiber density (IENFD) in skin punch biopsy samples.- What is the IEFND in the calf, distal thigh, proximal thigh, and arm in ME/CFS patients vs. normal controls?
- What is the thigh:calf IEFND ratio in ME/CFS patients vs. normal controls?
- What is the rate of SFN in ME/CFS versus MS, Sjogren's syndrome, etc.?
- Can SFN be identified in ME/CFS patients reliably? Can non-invasive tests be used?