Imaging technique for MS patients

Potential new guideposts for episodes of optic neuritis

An approach known as magnetic resonance diffusion tensor imaging (DTI) may allow practitioners to estimate the chronic effects of optic neuritis three months in advance, according to results of a recent study. Optic neuritis is a condition that often affects multiple sclerosis (MS) patients, said Robert T. Naismith, M.D., assistant professor of neurology, Washington University, St. Louis.
MS patients frequently struggle with a myriad of symptoms. “Optic neuritis can present with decreased vision and eye pain that’s worse with movement from side to side,” Dr. Naismith said. “The pain is worse with movement because the optic nerve gets inflamed, and when patients move their eyes they tug on the optic nerve and it creates a sensation that is unpleasant.” Affected patients often describe their vision in a few different ways. “Typically people will say that they have decreased vision in the center,” Dr. Naismith said. “They may describe it as a fog, a graying, or like looking through water or a cloud.” While most people ultimately do well with the condition, several episodes can take a toll.
“The issue is for those people who don’t do well and for those with MS who have multiple episodes,” Dr. Naismith said. “Because we know that people with MS after a number of years do have trouble with their vision,” Dr. Naismith said. One worry for MS sufferers with optic neuritis is that, to this point, there has been no telling who will do well and who will not.
In the recent study published in the December 2008 issue of Neurology, investigators set out to determine whether they could predict clinical outcomes for those with the condition. In animal models, strides had already been made in distinguishing different pathologies. The work broadens the idea of MS as a disease strictly of demyelination and has refocused it on the theory that the nerve itself is also involved.
Looking for axial damage

“The myelin can recover and the body can repair that to some degree,” Dr. Naismith said. “But we think the axon has very limited or no capacity to repair itself.” He hoped to be able to identify those with damage to their axons, who, it was believed, would have poorer outcomes. “This has been worked out in animal models, and this was really our first effort to bring it into humans in the optic nerve,” Dr. Naismith said. Investigators hoped that imaging technology such as the DTI test, which tracks water diffusion in tissue using a rapid series of MRI scans, could help. They thought that since inflammation and the resulting cell injury would likely alter water diffusion in the affected tissues, by tracking this they might be able to predict whether an MS flare-up would result in lasting damage.
To take a closer look, investigators launched two sub-studies. One of the studies targeted those experiencing their first episode of optic neuritis. Investigators here brought 12 healthy patients and 12 MS patients with optic neuritis back within 30 days of a flare-up and conducted a battery of clinical tests including visual acuity, contrast sensitivity, optical coherence tomography, visual evoked potentials (VEPs), and DTI, as well as an initial MRI. The second sub-study used the same sort of tests on 28 patients who had had optic neuritis in the past. Investigators wanted to correlate these tests to see how the patients’ recoveries matched up with what the MRIs showed, Dr. Naismith explained.

Finding testing correlations

In the acute study, investigators found some promising results. “There was a correlation between one of the diffusion parameters, axial diffusivity, and how that drops, with how visual recovery took place three months later,” Dr. Naismith said. Axial diffusivity looks at the water diffusion along the length of a patient’s optic nerve. Investigators here found that for healthy subjects this averaged about 1.66 micrometers squared per millisecond. However, levels dipped by up to 0.45 micrometers squared per millisecond for those with acute optic neuritis.
“We really want to have more patients and extend it out to six and 12 months,” Dr. Naismith said. “But it was at least encouraging that we’re going in the right direction.” Likewise, for those who had had optic neuritis previously, investigators also found some important indicators. “We found a very strong correlation with all of the clinical tests,” Dr. Naismith said. “Most notably, optical coherence tomography had a high correlation, but so did VEPs, contrast sensitivity, and visual acuity.” As a result, Dr. Naismith thinks that this technique could offer substantive information to practitioners. “I think that we have a technique to measure the integrity of the tissue within the optic nerve in a way that correlates pretty well with how we measure clinical vision,” he said.
For Dr. Naismith and his fellow researchers this work is rewarding for a broader reason as well—it offers an important proof of concept. “We wanted to look at the optic nerve to really validate the use of diffusion imaging in humans,” Dr. Naismith said. “The optic nerve is a relatively simple system with well-defined end points to look at, so before we launch into looking at the brain and the spinal cord this was a good place to start.”

Editors’ note: Dr. Naismith has no financial interests related to his comments.

Contact information

Naismith: naismithr@neuro.wustl.edu