New study: evidence for a role of cytomegalovirus in Susac syndrome

An international working group on Susac syndrome has taken an important step towards how the disease develops. The study was led by University Hospital Münster together with the clinics in Bochum, Essen, Düsseldorf, Berlin and Freiburg, and Ghent University Hospital (Belgium), in collaboration with the European Susac Consortium (EUSAC) and the International Susac syndrome Consortium (I-SuSaC).

Please note: The results have been released as a preprint. This means they are publicly available but have not yet been reviewed by independent expert, and individual findings may still change.

What was already known

We had previously shown that in Susac syndrome, certain immune cells - specifically, cytotoxic  T cells - mistakenly attack the small blood vessels of the brain, retina, an inner ear. What triggers this misguided immune response was unknown. 

What is new

We studied one of the largest groups of people with Susac syndrome assembled worldwide. Every patient tested carried antibodies against cytomegalovirus (CMV) – 70 of 70 in Germany and 13 of 13 in an independent Belgian group.

For context: CMV is very common, and roughly half of adults in Germany carry it. After infection, it remains dormant in the body for life, so antibodies alone only show that contact with the virus occurred at some point.  What stands out is that among the patients there was not a single exception.

• We also found two further features: T cells in people with Susac syndrome respond unusually strongly to CMV. Strikingly, very similar T cells in different patients target the same component of the virus.
• There was evidence of repeated reactivation of the virus. In some individuals, viral genetic material (DNA) was detectable in the blood, particularly during phases of disease activity.

A possible explanation

The results are consistent with the following model: CMV infection at some point before disease onset  → activation of certain T cells → misdirected response against the small blood vessels → Susac syndrome

Thus, CMV could be a trigger or driver of the disease.

What the study does not show

The study does not prove that CMV causes  Susac syndrome.

CMV is very common while Susac syndrome is very rare, so, the virus alone cannot explain the disease. It remains  open whether viral activity precedes the disease or arises as a consequence of the altered immune response. Answering this will require studies that follow patients over time.

What this means for you as a patient

• Your treatment does not change. Because the condition involves a malfunction of the immune system, immunotherapy with cortisone, IVIG, and other medications remains the treatment of choice.
• No recommendation for antiviral treatment can be derived from these data. Whether antiviral drugs, possibly combined with immunotherapy, will have a role must first be tested in clinical trials.
• There is currently no need to request a CMV test on your own initiative. A positive CMV antibody test is expected in about half of all adults and says nothing on its own about the disease.
• Please do not stop any medication, and raise any questions about these findings with your treating clinic or physician.

Thank you

Our thanks go to all the patients who have provided blood samples over many years. A study this size in such a rare disease would not have been possible without them.

Link to the reprint: Universal seropositivity, markers of recurrent reactivation, and a convergent T-cell response implicate cytomegalovirus in Susac syndrome | Research Square