Sensory nerve function preserved in SMA adolescents, adults: Study
'Preserved sensory integrity of the median nerve' in most patients
Most adolescents and adults with spinal muscular atrophy (SMA) have normal sensory nerve function, even those with long-lasting disease, regardless of SMA type, a study in the Netherlands shows.
Nerve conduction tests had abnormal results in about 6% of the patients, which was about what was seen in healthy participants.
“Our findings suggest the preserved sensory integrity of the median nerve,” wrote the study’s researchers, who said more research is needed to see if this “extends to other peripheral nerves.” The median nerve controls arm movement and sensation. Peripheral nerves are those outside the brain and spinal cord. The study, “Sensory Nerve Action Potential Analysis in a Cohort of Patients With Spinal Muscular Atrophy Aged 12 Years and Older,” was published in Muscle & Nerve.
SMA is mainly caused by mutations in the SMN1 gene that result in little or no production of the survival motor neuron (SMN) protein. This leads to the progressive loss of motor neurons, the nerve cells that control voluntary movements, while sensory function has been assumed to be unaffected.
Recent studies suggest sensory neurons, which are activated by sensory input from the environment, may be affected also, however, leading researchers to conduct a longitudinal study to assess sensory integrity in a group of patients followed at the Netherlands SMA Center in Utrecht. A total of 103 patients, ages 13-67, were included. A group of 53 age- and sex-matched healthy people were included as a reference.
Measuring SNAP
Almost half the participants had SMA type 3 or type 4 (48%), while 44% had type 2, and 8% had type 1. These disease types differ with respect to the age of symptom onset and severity. SMA type 1 is the most severe, with onset before six months of age, and SMA type 4 is the mildest form, with symptoms starting in adulthood.
All SMA type 1 patients and most of those with type 2 (87%) had three gene copies of the SMN2 gene, while those with SMA types 3 or 4 most often had four copies (58%). A higher number of copies of SMN2, a backup gene that contributes small amounts of functional SMN, is associated with milder forms of the disease.
The group with SMA type 2 was significantly younger than those with type 3/4 disease and the healthy controls.
Electrical activity in the median nerve was measured as the maximum sensory nerve action potential (SNAP). A reduction in SNAP amplitude suggests nerve fiber damage.
Overall, maximum SNAP was higher in people with SMA than in controls (62 vs. 46 microvolts [mcV]), particularly with SMA type 2 (77 mcV). Maximum SNAP decreased with age, a trend that was particularly steeper in SMA type 1 patients.
Maximum SNAPs were abnormal, that is, lower than 17 microvolts, in six patients (6%), which was comparable with age-matched healthy controls (8%). Abnormal maximum SNAP was most prevalent in those with SMA types 1 and 2 who were younger than 50, while there were no differences between SMA types in older patients.
Maximum compound muscle action potential (CMAP), which records the combined electrical signals produced by a group of motor neurons when the muscle is activated, was significantly lower in SMA patients than healthy controls (5.1 vs. 9.5), and in those with SMA type 1 or 2 over those with type 3 or 4 (2 vs. 3.5 vs. 7.1). There was no association between SNAP and CMAP in patients overall, after adjusting for disease type and age.
After more than year of treatment with Spinraza (nusinersen) for 47 patients or about a year with Evrysdi (risdiplam) for 43 patients, the maximum SNAP was similar to pretreatment values.
“Our findings indicate preserved sensory integrity of the median nerve in the large majority of a representative cohort of adolescents and adults with SMA, including those with longstanding disease,” the researchers wrote.
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