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Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS) Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia Leading Research. Delivering Hope.Open Medicine Foundation® Canada

Driving research of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS),
Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia and Long COVID.

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Herpes Simplex Encephalopathy
and the Development of ME / CFS

STUDY AIM
To investigate the correlation between biomarkers for brain injury and long-term neurocognitive outcome, and the interplay with intrathecal inflammation, in patients with herpes simplex encephalitis (HSE).
LEAD INVESTIGATORS
  • Jonas Bergquist, MD, PhD, Prof, Director ScD
  • Gabriel Westman, MD, PhD, Assoc Prof
  • Wenzhong Xiao, PhD
UPDATES AND POTENTIAL
  • CSF has been collected from an initial cohort of HSE patients and we have identified 890 proteins using LC-MS technologies. Responses of these proteins are being evaluated within the context of cognitive outcome. Data have been sent to the Computation Center at Harvard.
  • Patients with N-methyl-D-aspartate receptor (NMDA-R) antibodies after three months may be associated with persistent, severe neurocognitive dysfunction (p<0.006).
  • Based on data analysis the team has identified a central mechanism for neuronal dysregulation that shows up already early in the disease process and we could foresee those individuals with most severe outcomes.
  • In parallel, plasma metabolomics data (NMR + LC-MS) have been analyzed and resulted in close to 1,500 metabolites or metabolic ratios.
  • Clinical data sent to Melbourne for additional analysis. The Computation Center at Harvard will support with the Multi-Omics correlation.

STUDY HYPOTHESIS AND DESCRIPTION

The further understanding of the post-viral fatigue phenomenon that many HSE patients present with could give new insights in the initial episode of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME / CFS) since very many of the patients (70-80%) reports on an initial infection (eg mononucleosis) in the onset of the disease.

Our findings could give predictive evidence of long-term neurocognitive outcome in HSE, and suggest a causative chain of events where brain tissue damage increases the risk of subsequent prolongation of CSF inflammation and post-viral fatigue. The data could provide guidance for a future intervention study of immunosuppressive therapy administered in the recovery phase of HSE and other viral infections with neurological sequelae.

OBJECTIVES

Illustration - transparent body leaning forward. The brain is highlighted. A total of 50 adult/adolescent HSE patients were included in a prospective cohort. Study subjects underwent repeated plasma/CSF sampling (Day 0, 14 and 90) and brain MRI the first 3 months along with cognitive assessment by Mattis Dementia Rating Scale (MDRS) during 24 months. Initially, CSF samples will be analyzed for biomarkers of brain injury, inflammation and synaptic damage using proteomics (both MS-based screening and targeted Olink based panel). This could be complemented with a metabolic profiling of the plasma concentration of around 550 targeted analytes in plasma. The pre-defined primary analysis will be the correlation of CSF biomarkers and MDRS followed by evaluation of post-viral fatigue and ME.

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Microvesicles and viral sequencing
Microvesicles are a type of extracellular vesicle that is released from the cell membrane. Vesicles are small, fluid-filled sacs or vacuoles within the body. Sequencing is a technique used to determine the exact sequence of bases (A, C, G, and T) in a DNA (or viral) molecule.
NMR Metabolomics
NMR (Nuclear Magnetic Resonance) is an instrument/tool used to perform metabolic studies, metabolic profiling, and metabolomics in biofluids and tissues for more than 40 years using magnetic fields. There is a very close connection between metabolic measurements and NMR. This connection has flourished because of NMR’s many unique strengths for characterizing complex mixtures’ chemical composition.
Proteomics
The large-scale study of proteins, which are large, complex molecules that are required for structure, function, and regulation of the human body's tissues and organs.
Immune cell profiling
The immune system has many important regulatory roles in disease development and progression. Given the emergence of effective immune therapies, reliable predictors of response are needed. Immune cell profiling determines response by evaluating immune cell populations from treated and untreated samples. For our purposes, we will evaluate the white blood cell response to the viral infection using a process called “Cytof.”
Leukocyte Genomics
A leukocyte is a colorless cell circulating in the blood and body fluids and is involved in counteracting foreign substances and disease. A genome is all genetic material of an organism. Genomics is a biology field focusing on the structure, function, evolution, mapping, and editing of genomes. Therefore, leukocyte genomics is the study of all genetic material of leukocytes.
Metabolomics
Metabolomics is a way to study metabolism – that is, through measuring amounts of the metabolites (small molecules) produced by our bodies as we convert food into energy and other molecules that our cells need to survive. Metabolomics technology is ‘large-scale,’ meaning that several thousand metabolites can be measured from a single sample of e.g., blood or urine.
Micro RNA
Cells use Micro RNA to control whether a particular gene is making too much, too little or the normal amount of its protein at a particular time.
Autoantibodies
Antibodies that react with self-molecules and that occur in healthy individuals and are referred to as natural antibodies or autoantibodies.
Extracellular DNA for viral reactivation and Mitochondrial DNA
exDNA (extracellular DNA), exDNA is often secreted actively and is used to perform several tasks, thereby offering an attractive target or tool for biotechnological, medical, environmental, and general microbiological applications. Viruses are intracellular parasites that rely to a significant extent on the host cell for replication. Viral reactivation occurs when an active replication of the viral genome results in a lytic (degradation of the cell) infection characterized by the release of new progeny (descendant) virus particles.