The MS Cog Fog

Neuropsychiatrist aims to detect and decipher dysfunctional cognition in this demyelinating disease of the brain and spinal cord

Dr. Anthony Feinstein

Dr. Anthony Feinstein's findings that people with MS have less inattentional blindness could be areal-world measure of distractibility in these people.

Photo: Doug Nicholson

Multiple sclerosis (MS) is an unpredictable disease of the central nervous system and the most common cause of neurological disability in young to middle-aged adults. Canada has the highest prevalence in the world: about 100,000 Canadians have MS.* Although symptoms can be physical, including blurred vision, muscle weakness and difficulty with balance, MS can also affect cognition: 40% to 70% of people with MS will have some form of impairment—cloudy thinking, poor recall and high distractibility, for example.

Dr. Anthony Feinstein is a neuropsychiatrist at Sunnybrook and scientist at Sunnybrook Research Institute who sees about 500 patients in his MS clinic. In his experience, people with MS want to know if and how their brains are affected. “You want to know about your disease,” he says. “If you have cognitive difficulties, it’s not just an abstract finding. It will predict difficulties with work, with relationships, with recreational activities—it’s got practical implications for how individuals lead their lives.”

It is estimated 20% to 30% of patients show early signs of cognitive impairment. Wait times for neuropsychological testing can take many months. Full cognitive testing is limited by the cost of resources and a shortage of neuropsychologists to administer the lengthy tests in a busy medical setting. To address this, Feinstein and colleagues developed a short, computerized battery of tests for MS patients to complete in the clinic.

“The tests detect the speed with which you think, and they look at your working memory. We focus on these two aspects of cognition because we know that they are commonly affected in MS,” he says.

Feinstein and colleagues enrolled 138 patients aged 18 to 63 years from MS clinics at Sunnybrook and St. Michael’s Hospital. Patients were organized into one of four groups based on their disease subtype: clinically isolated syndrome (an individual’s first neurological episode); relapsing-remitting (unpredictable episodes when new symptoms appear or existing ones get worse, interchanged with a relative absence of symptoms); primary progressive (a slow increase in disability, without relapses); and secondary progressive (often follows relapsing-remitting MS; the disease begins to worsen steadily). They had to complete three computer-generated problem-solving tests. The total test time was 10 minutes.

His team evaluated the degree to which patients were able to achieve particular aims and how quickly they could do it. Immediately after the tests were completed, a neurologist reviewed the results.

They found that the battery was able to identify cognitive differences among the four groups of patients that spanned the range of MS subtypes, including those with clinically isolated syndrome.

“So you get a very quick assessment there in the clinic. That was the aim behind developing this study,” he says.

With results published in the European Journal of Neurology in 2014, Feinstein and colleagues now propose to use the computer-generated test in the MS clinics at Sunnybrook and St. Mike’s, which together see more than 7,000 patients. He says the next step in this research is to incorporate real-life distractions—a ringing telephone, for example—to do the same test in a busy clinical setting.

Monkey? What Monkey?

In another study led by Feinstein, published in the journal Neurology, researchers looked at “inattentional blindness,” a phenomenon whereby individuals fail to notice an object in plain sight. Although researchers have studied selective attention in individuals with no identified cognitive problems using the ‘Gorilla in the Room Test,’ Feinstein was the first to apply the paradigm to people with MS, who, in general, have difficulty paying attention, to measure their distractibility.

Healthy fiber, within a nerve cell

Within a nerve cell, a healthy fiber, or axon, is protected by intact myelin (bottom). This “insulation” helps to conduct electrical impulses smoothly and quickly, so that the brain and body can communicate and function properly.

In multiple sclerosis, myelin is damaged (top), it is thought because the immune system attacks its own brain, spinal cord and optic nerve. These attacks strip myelin from the axon, leaving small scars—scleroses—also called plaques or lesions. These demyelinated areas disrupt brain-body communication. Problems then develop, like muscle weakness, fuzzy thinking or blurred vision, depending on where the damage is.

Illustration: ©

His group examined 68 people with MS aged 18 to 59 years at Sunnybrook’s and St. Mike’s MS clinics. Patients were shown a 30-second video in which three people wearing white shirts passed a basketball to one another, while another three people in black shirts passed a different basketball to each other. Patients were instructed to count the number of passes made by the players wearing white only. Halfway through the test, a person wearing a gorilla suit wanders into the scene waving his hands, and then leaves.

His group examined 68 people with MS aged 18 to 59 years at Sunnybrook’s and St. Mike’s MS clinics.

“We came up with this really interesting finding that if you have attentional problems, then paradoxically you have less inattentional blindness because you are just so distractible. Patients are seeing the gorilla that [more than 50% of] healthy people are missing, but they are not counting the passes accurately,” he says. “The implication is really quite significant, and it’s a further marker of how their cognition is impaired.

“What might be interesting is that a test like this may help explain why individuals with high premorbid intelligence, who do well on conventional cognitive tests, still end up struggling when at work.”

Of course, not everyone with MS will have cognitive issues, he notes: “If your disease is primarily in the spinal cord, for example, then you may have no cognitive difficulties. If you have a light lesion load in the brain, or your brain hasn’t atrophied, then you may be one of those individuals who escape cognitive difficulties.”

Feinstein is now running a study of 40 people with MS using functional magnetic resonance imaging to capture what is happening in the brain during inattentional blindness.

“We hope to get a better understanding of an interesting cognitive phenomenon. That’s what brain imaging can do—help you understand how the brain functions,” he says, adding, “There are unfortunately no immediate clinical benefits for patients from a study like this, but it does help us understand how the MS brain works.”

He acknowledges that therapy for cognitive difficulties lags behind research. “It’s one thing to detect the problem, it’s another to provide the treatment.” Feinstein notes that medications generally don’t work, with the possible exception of amphetamines, and that in many cases teaching people how to compensate for their cognitive problems is the best they can do. “We teach the patients to maximize their strengths, while working around their limitations.”

For the field of MS more generally, Feinstein expresses hope. “When I did my PhD 22 years ago there were no treatments for MS apart from steroids. Now patients with relapsing-remitting disease have a choice of disease-modifying drugs that can help them. The whole therapeutic landscape for some patients has changed dramatically, and there are multiple new drugs and some in the pipeline that offer promise. There’s an enormous amount of energy and interest in MS research now.”

Feinstein’s research is supported by the funding agencies the Canadian Institutes of Health Research and the Multiple Sclerosis Society of Canada, and the company Biogen Idec.