Research Sheds Light on Hidden MS Symptoms

Many people are familiar with the telltale signs of multiple sclerosis: difficulties with seeing and walking, numbness and fatigue.

Cedars-Sinai Multiple Sclerosis Center Director Nancy Sicotte, MD, is using advanced imaging techniques at the Biomedical Imaging Research Institute to discover the link between depression and inflammatory autoimmune diseases such as multiple sclerosis. The aim is to better treat patients experiencing depressive symptoms.

However, Cedars-Sinai multiple sclerosis specialist Nancy L. Sicotte, MD, said there are other "hidden symptoms" that can be just as debilitating. These include depression, fatigue and cognitive impairment. Many of these symptoms may be related to selected brain regions.

"There are multiple reasons why people would be depressed," she explained. "But we think that a lot of it is actually disease driven, not because people are ‘sad because they have MS.'"

Sicotte, the director of the Multiple Sclerosis Center and Neurology Residency Training Program at Cedars-Sinai, said while there is no direct relationship between depression and physical disability, depression seems to be related to changes in certain structures in the brain.

Sicotte has her sights set on the hippocampus, the area responsible for mood and memory. She believes having an autoimmune disease, especially an inflammatory disease such as multiple sclerosis, is related to increase in depression.

More importantly, she said, hidden symptoms such as depression are frequently under-recognized and undertreated.

"I think it is very important that we draw attention to these hidden symptoms because they have huge impacts on patients' lives," Sicotte said. "In fact, a symptom like fatigue, which is very highly correlated with depression, is one of the main reasons why people stop working. It's not because they can't walk."

With the support of a National Multiple Sclerosis Society grant, Sicotte continues to study brain changes in multiple sclerosis through imaging, specifically to understand the underlying causes and potential treatments of multiple sclerosis-related depression.

The study is currently enrolling four groups, with 30 individuals in each of the following categories: patients with depression and multiple sclerosis; patients with no depression, who have multiple sclerosis; patients with only depression, and a final control group with neither condition.

Using imaging from the Biomedical Imaging Research Institute, Sicotte is able to look at the hippocampus and check for shrinkage.

"Typically when you have an MRI for clinical purposes the radiologist will collect images using standard acquisitions. But in our research study, we are doing more advanced imaging, including diffusion tensor imaging and resting-state functional MRI which allow us to detect more subtle changes that affect the MS brain," she said. "It's not your standard stuff you would get when you would go in for a clinical MRI."

In many neurological diseases, and in particular multiple sclerosis, imaging serves as a very important biomarker, or way to track disease activity. Imaging provides a window into brain changes that can be assessed frequently over time without resorting to more invasive types of testing.

Despite the utility of MRI in multiple sclerosis, "we need better imaging outcome measures to better predict disease progression and to test novel approaches that will be needed to assess newer multiple sclerosis therapies. These therapies will focus more on protecting and repairing the nervous system," Sicotte said. "Having better ways to capture these types of treatment effects is intriguing. These approaches allow us to better see more of what's going on in the nervous system, but completely non-invasively, which is very powerful."

In addition, she said, "these techniques can be used to track other neurological disorders such as Alzheimer's or Parkinson's diseases."

Sicotte is also working with Enrique Lopez, PsyD, and Kimberly Smith, PsyD, who are measuring cognitive function including learning and memory among the study participants. These are important cognitive behaviors to assess among these patients.

"The hippocampus is interesting to study because it's the part of the brain that helps to form and retain new memories, and it is important in learning," explained Lopez, who is a clinical neuropsychologist at Cedars-Sinai's Department of Psychiatry and Behavioral Neuroscience and for the Department of Neurology.

"When people are depressed, they are not really assessing or learning as well and efficiently, and so we wonder about that," he said. "What Dr. Sicotte is trying to figure out is what is causing the most shrinkage of the hippocampus. Is it the depression alone, or is it the MS alone, or is it both?"

He said this is important, because then patients have a better idea as to whether they have cognitive, learning or memory difficulties.

Sicotte said her team also is looking to create better research pathways.

"Part of the reason to do the research is to understand the underlying structural brain changes that are associated with depression, so we can see if they are modifiable and then we would know what to track for a clinical trial targeting MS-related depression," Sicotte said. "One therapeutic option that could be studied is finding ways to reduce cortisol and stress hormones that seem to be related to depression and brain changes.

"I think this research is helpful for patients because it's not just minimizing their symptoms and saying they're depressed – it's recognizing that it's actually a part of the disease process."

And when a patient is depressed, the body becomes stressed and strained – leaving no room for healing, Lopez said.

"Your immune system is off, your body is not working as efficiently," he said. "This is why it's important to uncover what is happening with MS and depression."

For Sicotte, it all boils down to making sure patients don't suffer needlessly with depression, a treatable condition.

"I think it's important for MS neurologists to make a point to ask about it and treat it appropriately because we have good treatments for depression," she said. "Plus, I think that our research will help bring it out of the shadows and increase awareness of this hidden MS symptom."