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It is not only the heart that has the chambers, the brain too. Its four ventricles are connected to the spinal canal and are filled with a clear fluid called cerebrospinal fluid, which removes metabolic waste from neurons. When the brain becomes inflamed, immune cells also circulate in this fluid. This is the case with diseases such as multiple sclerosis (MS), in which the immune system attacks the protective layer of the body around the axons (nerve fibers) in the brain and spinal cord. This triggers the inflammation which ultimately leads to the destruction of neurons.
Usually, the ventricular volume of the brain remains fairly constant. Dr Sonia Waiczies and her colleagues from the Max Delbrück Center for Molecular Medicine of the Helmholtz Association (MDC) and the Charité-Universitätsmedizin Berlin made a discovery in an animal model of MS in 2013: they observed that ventricular volume increased compared to course of the disease. When they used an antigen to cause encephalitis (inflammation of the brain) in the mice, the MRI clearly showed that the ventricles were expanding. “Everyone thought it was a sign of brain atrophy,” Waiczies recalls.
The swelling goes down again
As the ventricles of the brain get bigger, the brain has to get smaller. After all, the surrounding skull bone won’t let it go anywhere else. Inflammation causes brain tissue damage, but atrophy – i. H. Massive loss of brain volume – not always instantaneous. And if so, the process would be irreversible. “That’s why we ran a number of other animal experiments and monitored brain volume for two months,” says the neuroimmunologist and lead author of the current study. About ten days after the encephalitis was triggered, the rodents’ brain ventricles were significantly enlarged. Then, a few days later, they returned to normal when the symptoms disappeared. Just like patients, they would develop temporary relapses – albeit with milder symptoms than in the beginning – and the ventricles would enlarge again.
Waiczies, who also works as an MRI scientist, finds these results quite logical: “For example, if I have an inflamed joint, it edema and swells. Once the inflammation subsides, the swelling will also subside. “The team is interested in the molecular mechanisms underlying these changes. But first they wanted to know if their findings were clinically relevant.
Archive data confirms the new results
Enlarged brain ventricles in people with MS are commonly considered a sign of brain atrophy. A reduction in ventricle size has never been reported in patients. What does this observation mean for MS patients? And can the results be transferred from mice to humans? In the current study, the researchers tested this using large MRI datasets from MS patients. From 2003 to 2008 they took part in a clinical trial at the Charité to test the effectiveness of a new MS drug. “I was involved in the immunological planning and evaluation of this study and I knew that the MRI data generated is large and robust,” says Waiczies.
The diagnosis of multiple sclerosis is made on the basis of MR images and by analyzing the cerebrospinal fluid obtained by perforating the spinal cord. Regular scans allow for a better prognosis of the course of the disease. In this study, participants received a monthly MRI scan. Now countless images had to be viewed and statistically evaluated. Lead author Dr. Jason Millward, a neuroimmunologist at MDC and Charité and a statistics enthusiast, has started work on the new study.
“The key factor was the number of measurements made over time, which gave us a unique opportunity to see if patients were showing similar trends,” Millward explains. In fact it was: “Most patients with relapsing-remitting MS had fluctuations in ventricular volume, just as we observed in mice.” Interestingly, Millward also noted that with the changes in ventricular volume, the patients appeared to be at an earlier stage of the disease.
“We are used to seeing ventricular enlargement in other neurodegenerative diseases – like Alzheimer’s or Parkinson’s. In these diseases, however, the ventricles do not expand, but continue to be reversible, “explains MDC Professor Thoralf Niendorf, who also works at the Center for Experimental and Clinical Research (ECRC), a joint institution of MDC and Charité: “Regular monitoring of ventricular volume in MS patients could help distinguish transient fluctuations from progressive brain atrophy.” This would also allow for better tailoring of therapies to the individual patient.
Professor Friedemann Paul, a clinical neuroimmunologist at Charité and along with Waiczies and Niendorf, the lead author of the current study, adds: “From a clinical perspective, examining ventricular volume fluctuations in routine MRI scans of patients could be an interesting for monitoring disease progression or immunotherapy
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