Amyotrophic Lateral Sclerosis – Is An Early Diagnosis Possible?

Lou Gehrig had it. Professor Stephen Hawking has it. Although the incidence of amyotrophic lateral sclerosis (ALS) is low as compared to other diseases, with only about 5600 new cases reported every year in the United States, this neurological ailment is significant.

Typically, it affects people between the ages of 40-75 with more men being afflicted than women. In ALS, the motor neurons lose the ability to communicate with muscle cells causing the limbs to lose motility. Gradually, muscle cells atrophy, or shrink essentially because they are not “used” or controlled by motor neurons in the brain and spine anymore. Patients are able to use their mental faculties and have sufficient control over core bodily functions but lose the ability to manipulate limbs. The disease is progressive and survival rates are approximately 50% for three years post diagnosis which decline to 20% for five years post diagnosis. A small fraction of patients, about 10%, can survive for up to ten years post initiation of ALS.

As with other neurodegenerative diseases, the exact causes of ALS are not yet known to us. It is postulated that proteins that bind to ribonucleic acid (RNA) like FUS are involved in the progression of ALS. Oxidative stress in the form of reactive oxygen species also contributes to the pathogenesis of ALS. Given that the molecular nature of the disease is not yet fully understood, therapeutic options are limited and prevention or early diagnosis are the best options for patients.

In a recent study, Crew and colleagues from the Miami University have published findings of significant diagnostic potential. The onset of ALS in patients is likely to be characterized by a preceding period of metabolic changes in motor neurons, even if obvious symptoms of ALS are absent. In order to understand these changes, these researchers used magnetic resonance spectroscopy (MRS) to estimate the ratios of metabolites like choline (Cho), N-acetylaspatrate (NAA), myo-inositol (Myo) and creatine (Cr) in the neck region of people who were mutant for an enzyme , Superoxide dismutase (SOD, and therefore more likely to suffer from neurodegenerative diseases like ALS), normal individuals and patients with a confirmed diagnosis of ALS. People with the mutant enzyme did not show symptoms of ALS at the time the study was conducted. NAA is a marker for loss of neurons. It is usually estimated as an absolute value or as a ratio of other metabolites like Cho and Cr.

Their results show that the ratios of NAA/Cr and NAA/Myo were reduced in people with the mutant enzyme to the same extent as in people with a confirmed diagnosis of ALS. In both these groups, these two ratios were reduced by ~40% when compared against similar ratios from healthy individuals. The ratio of Myo/Cr was reduced by ~10% in people with mutant SOD but not in normal individuals or in ALS patients. Likewise, the ratio of NAA/Cho was reduced by 24% in ALS patients compared against a similar ratio in healthy subjects. However, subjects with mutant SOD did not show a similar reduction in the NAA/Cho ratio.

These results show that it may be possible to understand presymptomatic stages of ALS in high risk groups with the help of a non-invasive technique like magnetic resonance spectroscopy and arrive at molecular criteria that define the onset of ALS. The technique may also be developed into a fast and non-invasive diagnostic tool.


Carew JD, Nair G, Pineda-Alonso N, Usher S, Hu X, & Benatar M (2011). Magnetic resonance spectroscopy of the cervical cord in amyotrophic lateral sclerosis. Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases, 12 (3), 185-91 PMID: 21143004

Carew JD, Nair G, Andersen PM, Wuu J, Gronka S, Hu X, & Benatar M (2011). Presymptomatic spinal cord neurometabolic findings in SOD1-positive people at risk for familial ALS. Neurology, 77 (14), 1370-5 PMID: 21940617

Federico A, Cardaioli E, Da Pozzo P, Formichi P, Gallus GN, & Radi E (2012). Mitochondria, oxidative stress and neurodegeneration. Journal of the neurological sciences, 322 (1-2), 254-62 PMID: 22669122

Gitler AD (2012). TDP-43 and FUS/TLS yield a target-rich haul in ALS. Nature neuroscience, 15 (11), 1467-9 PMID: 23103989

Image via David Fowler / Shutterstock.

Shefali Sabharanjak, PhD

Shefali Sabharanjak, PhD, is a professional science and medical writer. She holds a doctorate in Cell Biology from the National Center for Biological Sciences. Clear and precise communication is her forte.
See All Posts By The Author