MRI Reveals Multiple Regions of the Brain Attacked by ALS

ALS is a fatal neurodegenerative disease that ultimately leaves patients unable to move, breathe, or swallow. Earlier studies have shown approximately 50% of patients with ALS also have mild cognitive and behavioral changes, but between five and 15% of patients can have severe changes resulting in dementia. In Canada, between 2,500 and 3,000 people live with the disease. Most die within two to five years of diagnosis.

Dr. Sanjay Kalra, a researcher in the faculty of medicine & dentistry division of neurology at the University of Alberta (Edmonton, Canada) and a practicing neurologist, has published two articles, one published on Jul 21, 2011 and the other in February 2011 in the American Journal of Neuroradiology, providing evidence that ALS affects more than just the motor cortex, the part of the brain responsible for motor function.

“ALS was previously thought to be a disease restricted to the motor system causing only weakness,” said Dr. Kalra, the lead investigator in both articles. “But a significant proportion of people with ALS also have cognitive and behavioral changes. We wanted to know how ALS was impacting other parts of the brain to cause these symptoms. There is increasing evidence from pathological studies of ALS patient’s post-mortem that not just the motor system is involved. Our research supports this and demonstrates in those living with ALS, that the disease is indeed attacking other parts of the brain. The cognitive and behavioral changes we are seeing in patients are not reactive. They are not happening because someone is depressed or doesn’t have initiative because he is weak. Those changes are happening because there are biological and chemical changes in parts of the brain that are responsible for behavior and cognition.”

Dr. Kalra uses magnetic resonance imaging (MRI) scanning not to only look at images of the brain, but also as a way of measuring the levels of various chemicals in the brain. In his most recently published article, he looked at two different chemicals called N-acetylaspartate (NAA) and myo-inositol (mIns). NAA is known as a neural marker, which means it is only found in neurons, while levels of mIns increase when there is abnormal scarring in the brain.

“If NAA is decreased, it means neurons have died or they are not working. Many papers have shown NAA to be decreased in regions where you expect it to be decreased with ALS--the motor cortex. But our recent study shows that these levels are also decreasing in areas of the brain responsible for cognition and behavior” said Dr. Kalra. His paper published February 2011 looked at decreasing levels of NAA in the cingulate cortex--the first time MRI had been used to measure chemicals in this region of the brain in ALS. In addition, his most recently published paper, which came out late this summer, was the first to demonstrate that NAA was decreasing and mIns was increasing in the frontal lobe, even when there were no signs of cognitive or behavioral issues in patients. The frontal lobe is considered the hub for cognition and behavior in the brain.

Dr. Kalra would like to continue his research using MRI to monitor the changes in the brain of those who have ALS, and to examine new drugs. He is the leading researcher in Canada to use MRI scanning to study ALS. In November 2010, he was invited to give a presentation at Oxford University (UK). He first became interested in studying ALS when he was a neurology resident looking for a research project using MRI. He has continued studying the disease ever since.

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