Simple nerve signals may help track disease progression in SMA
Study finds signals tied to motor function are lower in SMA patients
Written by |
- Far-field potentials (FFPs), electrical nerve signals, may help track disease progression in SMA.
- People with SMA have lower FFP amplitude, which is linked to reduced motor function.
- FFP measurements may help monitor SMA disease progression in clinical and research settings.
Far-field potentials (FFPs), electrical signals recorded with surface electrodes after nerve stimulation, may help track disease progression in people with spinal muscular atrophy (SMA), a study suggests.
The strength of these signals, or FFP amplitude, was significantly lower in people with SMA than in healthy participants, but not significantly different from that seen in those with amyotrophic lateral sclerosis (ALS), another neuromuscular condition.
Findings suggest far-field potentials may help monitor SMA progression
“Incorporating FFP amplitude measurements into clinical assessments and trials may enhance disease monitoring and provide a reliable marker for tracking disease progression,” the researchers wrote. The study, “Utility of Far-Field Potentials as a Biomarker of Neurodegeneration in Spinal Muscular Atrophy,” was published in Muscle & Nerve.
In SMA, SMN1 gene mutations lead to a deficiency of the SMN protein, disrupting the health of motor neurons — the nerve cells that control movement — and causing muscle weakness and wasting.
The function of lower motor neurons, nerve cells in the spinal cord that directly control muscles, is commonly assessed using the compound muscle action potential (CMAP), which measures the strength of a muscle’s electrical response after nerve stimulation.
However, CMAP may not always accurately reflect nerve fiber loss. FFPs, which are less influenced by electrode placement, have emerged as a promising diagnostic and prognostic biomarker in ALS.
To assess the clinical utility of FFP in SMA, researchers in Australia recruited 13 participants with SMA, 19 with ALS, and 19 healthy controls at the Neuromuscular Clinic in Sydney. Participants with SMA had a median age of 33 years, a disease duration of more than 28 years, and were mostly women (61.5%).
In this group, most patients had SMA type 3 (76.9%), and the rest had SMA type 2. At the time of the study, four patients could walk, six could sit, and three were unable to sit. Among the five participants who were able to complete motor assessment using the Hammersmith Functional Motor Scale – Expanded (HFMSE), all showed mild motor impairment.
Functional scores indicate moderate impairment in SMA group
Based on the ALS Functional Rating Scale-Revised (ALSFRS-R), participants with SMA showed moderate functional impairment overall. While nearly one-third had not received a disease-modifying treatment, 38.4% were treated with Spinraza (nusinersen) and 30.8% with Evrysdi (risdiplam).
To measure FFP, the researchers stimulated the ulnar nerve at the wrist and recorded responses using surface electrodes placed on the hand and wrist. Results showed that FFP amplitude was significantly lower in people with SMA (4.1 millivolts, or mV) than in healthy controls (8.4 mV), and not significantly different from that seen in ALS patients (6.2 mV).
CMAP amplitude was also significantly lower in SMA than in ALS patients and healthy participants (4.4 vs. 7.9 vs. 11.6 mV). Other measures, including the motor unit number index, which estimates the number of surviving motor fibers, and the split hand index, which reflects muscle wasting in the hand, were also significantly reduced in both SMA and ALS patients compared with controls.
In SMA patients, higher FFP amplitude was associated with better upper-limb and fine motor function, as well as less overall functional impairment. According to the researchers, these results highlight FFP’s “potential as a sensitive biomarker of motor function in SMA.”
FFP amplitude linked to motor function and clinical measures
FFP amplitude also correlated significantly with the conventional CMAP amplitude. In contrast, participants’ age at assessment was not associated with FFP amplitude.
Additional analysis showed that FFP amplitude, but not CMAP, was an independent predictor of hand and arm function, as measured by the Revised Upper Limb Module (RULM) score. In turn, RULM scores were associated with both FFP and CMAP amplitudes, with a stronger relationship observed for FFP.
Overall, this study suggests FFP amplitude has “potential as a complementary neurophysiological marker of lower motor neuron dysfunction in SMA,” and “as a surrogate prognostic biomarker in SMA,” the researchers wrote. They noted that the number of participants with SMA was relatively small, highlighting the need for further studies.
