Muscle Ultrasound Could Be Important Tool in Flagging Late-Onset SMA

Muscle ultrasound may be a useful tool in diagnosing later-onset spinal muscular atrophy (SMA), according to a new study that compared the technique to physical examinations and electromyography (EMG).

The study was conducted by Jonas Alex Saute, MD, PhD, of the Hospital de Clínicas de Porto Alegre, Brazil, and colleagues, and published in the journal Neuromuscular Disorders.

The investigators noted that SMA is an autosomal recessive monogenic disorder marked by degeneration of the lower motor neurons in the spinal cord and caused by variants in the SMN1 gene. It is classified based on age of onset and level of impairment.

Diagnosis of SMA generally begins with clinical suspicions, Saute and colleagues said, with genetic testing among the first tier of complementary studies. Type I SMA, which can be diagnosed in infancy when babies are hypotonic and unable to sit, is generally a straightforward diagnosis. However, the diagnosis of later-onset forms (types II through IV) typically involves a more winding path, with neurophysiological and other complementary studies often performed before genetic testing in order to narrow differential diagnosis.

In the new study, Saute and colleagues zero in on another potential warning sign of SMA: the rapid, non-painful, involuntary muscle contractions known as muscle fasciculations.

“They are a common feature after injury of peripheral nerves by trauma or degenerative diseases such as amyotrophic lateral sclerosis (ALS) and SMA and, less frequently, Charcot-Marie-Tooth disease and spinocerebellar ataxias,” the authors noted.

Fasciculations can be identified with a neurological examination, EMG, or muscle ultrasound.

The investigators said that despite being common in SMA, muscle fasciculations have not been studied as a potential diagnostic marker for SMA.

Saute and colleagues therefore sought to evaluate the diagnostic properties of muscle fasciculations in patients with proximal muscle weakness, and then find out which method of identifying muscle fasciculations is most accurate.

The authors recruited 10 adolescent and adult subjects with SMA, half of which had type II and half of which had type III SMA, along with 9 subjects with genetic muscle diseases (gMD) for comparison.

The subjects all had proximal muscle weakness, and underwent a physical examination, muscle ultrasound, and EMG. The authors noted that 42% of enrollees declined EMG, limiting their ability to evaluate that method.

The physical examination had moderate inter-rater reliability at identifying muscle fasciculation broadly, but the authors said the reliability was poor in terms of quantifying the total number of muscles with fasciculation.

Muscle ultrasound, on the other hand, performed better. All of the patients with SMA and 3 of the subjects with gMD were found to have fasciculations, resulting in a sensitivity of 1 (95% CI, 0.69-1) and a specificity of 0.67 (95% CI, 0.3-93).

“Our results showed the highest diagnostic accuracy for muscle ultrasound, which presented 100% of sensitivity and higher specificity when considering the presence of fasciculations in 2 or more muscle groups,” the authors concluded.

Though the authors noted that all of their patients with SMA had muscle fasciculations, they cautioned that they were not suggesting that muscle ultrasound replace genetic testing.

“What this study suggests is that [muscle ultrasound] might help to guide clinicians in the diagnostic workup of patients with proximal weakness, being of greater utility when fasciculations are not clearly detected during inspection,” they wrote.

Thus, they said, a patient might ideally first undergo a physical examination, muscle ultrasound or EMG in order to confirm muscle fasciculation, and then, if positive, complete genetic testing to confirm an SMA diagnosis.

“These results might improve diagnostic guidelines for later-onset SMA, leading to earlier diagnosis, treatment and specific care,” the authors concluded.

Reference

Rocha dos Santos MA, Brighente SF, Massignan A, et al. Accuracy of muscle fasciculations for the diagnosis of later-onset spinal muscle atrophy. NeuromusculDisord. Published online July 2022. doi:10.1016/j.nmd.2022.07.395