Spinal muscular atrophy (SMA) is a disease whose manifestations have some similarities with ALS, however, it has a well-identified genetic origin (SMN1 gene) and as a result, several drugs have been approved. These drugs improve the health of patients but have various drawbacks.
This rare disease causes the loss of motor neurons and progressive muscle atrophy. It is usually diagnosed in early childhood and, if left untreated, it often leads to death. It can also appear later in life and in this case the disease progresses more slowly.
The common feature is a progressive weakness of voluntary muscles, with the muscles of the arms, legs and airways being affected first. Associated problems can include poor head control, difficulty swallowing, scoliosis, and joint contractures.
Although there is a large literature on the split hand phenomenon in ALS, knowledge remains limited for other motor neuron diseases, including SMA.
Early in ALS it is common for the thenar muscles (thumb muscles) to be affected and lose their usual volume, visually dividing the palm into two sections. This is oddly described as the split hand phenomenon or monkey hand phenomenon.
This phenomenon reflects the selective vulnerability of motor neurons characteristic of the disease. Conditions such as ALS, while also affecting motor neurons, tend to present with the classic split hand pattern, highlighting the differential pathophysiological mechanisms at play. However, the explanations for why these muscles are affected early in the disease are no clearer than in ALS. Furthermore, age-related atrophy can also present with the split hand phenomenon, complicating the diagnosis of ALS in older patients.
Muscle disuse is a common cause of muscle atrophy. The rate of muscle atrophy due to disuse is about 0.5% of total muscle mass per day. Older adults are most vulnerable to dramatic muscle loss with immobility. In SMA, as in ALS, loss of motor neuron function leads to muscle atrophy. A new study compared these losses in ALS and SMA.
To assess muscle loss in motor neuron diseases, the number of motor units is studied. A motor unit includes a motor neuron and all the skeletal muscle fibers innervated by the neuron's axon terminals, including the neuromuscular junctions between the neuron and the fibers. Groups of motor units often work together as a motor pool to coordinate the contractions of a single muscle.
The number of motor units per muscle can change due to aging, disease, or injury.
Motor unit number estimation (MUNE) is a technique that uses electromyography to estimate the number of motor units in a muscle.
Motor unit number estimation (MUNE) methods, such as MScanFit MUNE, provide accurate results. This study uses MScanFit MUNE to compare patterns of motor unit loss in SMA, ALS, and healthy controls. Key findings include:
Patients with SMA had more severe degeneration of the hypothenar muscles compared to the thenar muscles. The authors call this: The reverse split-hand phenomenon, in reference to the split-hand phenomenon in ALS. Patients with ALS had a traditional split-hand phenomenon, with more severe involvement of the thenar muscles.
Reinnervation in SMA: Evidence of compensatory nerve sprouting in the ADM muscle has been noted in SMA but not in ALS, highlighting distinct pathophysiological mechanisms in these two diseases.
For SMA, the APB muscle has emerged as an optimal biomarker to monitor disease progression and therapeutic response due to its resistance to degeneration.
Curiously, although the authors confirmed the correlation between MScanFit MUNE neurophysiological parameters and disease severity in SMA patients, they did not find convincing correlations between MUNE neurophysiological parameters and clinical variables in ALS patients, particularly with the ALSFRS-R scale. On this issue, although several studies have reported the correlation between MUNE values and the ALSFRS-R scale, others have not confirmed it.
Limitations and future directions The small cohort of AMS in the study and the lack of longitudinal data (over a period of several years) limit the conclusions. Future research should examine whether the reverse split hand phenomenon is exclusive to SMA and clarify why certain hand muscles are more vulnerable.