Robert Zivadinov, MD, PhD

Working with global collaborators, Robert Zivadinov, MD, PhD, is conducting research that may provide a biomarker for assessing new MS therapies.

UB Studies Link Thalamus Atrophy to MS; Suggest Evaluation Tool

Published June 10, 2013

University at Buffalo researchers and their global collaborators are building a growing body of evidence that links changes in the brain’s thalamus region to multiple sclerosis (MS).

“The location of the thalamus, its unique function and its vulnerability to changes wrought by the disease make [it] a critical barometer of the damage that MS causes to the brain.”
Robert Zivadinov, MD, PhD
Professor of neurology

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Researchers discuss thalamus studies and their significance for multiple sclerosis patients.

Changes in Gray Matter May Signal MS

Over the past three years, the researchers have published journal papers and presented studies that show the brain’s gray matter—which includes the thalamus—reflects important changes in the disease.

Captured through magnetic resonance imaging (MRI), those changes could allow clinicians to diagnose MS earlier and better monitor and predict the disease’s progression.

“In our recent studies, we have used large datasets to investigate the evolution of atrophy of the thalamus and its association with clinical impairment in MS, starting with the earliest stages of the disease,” says Robert Zivadinov, MD, PhD, professor of neurology, who has led much of the research.

Two studies were presented at the 2013 annual meeting of the American Academy of Neurology in March.

Research progress has been highlighted in a review paper, “The Thalamus and Multiple Sclerosis: Modern Views on Pathologic, Imaging and Clinical Aspects,” in Neurology.

New Direction in Understanding MS

The researchers’ line of inquiry marks a departure from traditional views.

MS has been perceived primarily as a disease of the brain’s white matter, in which myelin, the fatty material surrounding neurons that allows them to signal effectively, is gradually destroyed.

The thalamus, however, “is providing us with a new window on MS,” says Zivadinov. “Its location, unique function and vulnerability to changes wrought by the disease make [it] a critical barometer of the damage that MS causes to the brain.”

The thalamus plays a key role in a variety of neurologic functions, including motor and sensory function, the regulation of sleep and wakefulness, memory, emotion, consciousness, awareness and attention.

It functions as a kind of relay center in the brain, taking in sensory information and sending it to the cerebral cortex; it also processes information coming from the cortex.

Thalamus Atrophy IDs ‘Clinically Definite’ MS Risk

In one study, researchers found that atrophy of the thalamus can help identify which patients with a first episode of MS — known as clinically isolated syndrome — are at risk for developing clinically definite MS.

“Based on these findings, we think MRI should be used to determine which patients are at highest risk for a second attack,” explains Zivadinov.

Such a tool would be immensely helpful to clinicians, he notes.

The study, “Thalamic Atrophy is Associated with Development of Clinically Definite Multiple Sclerosis,” has been published online in Radiology.

Study Assesses Cognitive Decline in the Long Term

Another study, involving 81 MS patients, is the first to look at the evolution of thalamic atrophy over 10 years.

This study found that atrophy in the cortex and subcortical deep gray matter, including the thalamus, was significantly related to patients’ declining cognitive abilities.

“We found that cognitive dysfunction appears early in the course of MS and that thalamic atrophy plays a central role in predicting cognitive deterioration over the long term,” says Zivadinov.

A separate study found that the loss of thalamic volume and its tissue integrity can also predict cognitive impairment in MS patients.

Led by Ralph Benedict, PhD, professor of neurology, this study, “Clinical Significance of Atrophy and White Matter Mean Diffusivity within the Thalamus of Multiple Sclerosis Patients,” has been published in Multiple Sclerosis Journal.

Biomarker to Evaluate Novel MS Therapies

In the first prospective, longitudinal study of its kind, the researchers found associations between gray matter atrophy and physical disability progression in patients with relapsing-remitting MS—the most common and disabling type of MS.

The five-year study involved 180 patients.

The study results also point to the thalamus as a biomarker for assessing new therapies.

The study shows progressive pathology of the thalamus in all different MS disease types, including in pediatric MS patients, notes Zivadinov.

Therefore, “measurement of thalamic atrophy may become an ideal MRI outcome for MS clinical trials,” he says.

Gray Matter Injury May Be Early Warning Sign

In another study, Zivadinov and his colleagues found that injury in gray matter can be detected early in the MS disease process and is associated with a wide range of symptoms—from cognitive decline and motor deficits to fatigue and chronic pain.

These results offer further evidence of a potentially valuable tool for evaluating new treatments, as well as detecting, evaluating and predicting the course of MS.

“Atrophy in MS patients happens in the thalamus more rapidly than in other brain structures,” Zivadinov adds.

“It [also] is less affected by fluid shifts in the brain, an effect of anti-inflammatory drugs used in MS.”

Practical, Clinical Applications

The researchers now plan larger longitudinal studies “to comprehensively determine how best to apply these very promising findings,” Zivadinov says.

“Until now, existing information about thalamic involvement in MS has stemmed mainly from neuropathologic and neuroimaging studies with a limited number of subjects that contain no clear practical implications for clinicians,” he notes.

UB Fellows Support International Team

As part of an international team, UB researchers have been supported by an active fellowship program at the Department of Neurology’s Buffalo Neuroimaging Analysis Center (BNAC), which Zivadinov directs.

UB coauthors on the papers also include:  Bianca Weinstock-Guttman, MD, professor of neurology; Murali Ramanathan, PhD, professor of pharmaceutical sciences; Michael G. Dwyer, director of technical imaging at BNAC; and Niels Bergsland, integration director at BNAC.

Other co-authors are from Yale University; the Mayo Clinic; Louisiana State University; and the University of Texas Southwestern Medical Center in the United States, as well as VU University Medical Center (the Netherlands); Charles University (Czech Republic); University of Sydney (Australia); Tehran University of Medical Sciences (Iran); and two university hospitals in Norway (Stavanger and Haukeland).