This study revealed small but significant reduction in median nerve, nerve roots, nerve trunks, and most of the sites of ulnar nerve in patients with ALS compared to healthy controls, which supports previous studies that established reduction of CSA at peripheral nerve. For the first time, this article systematically and comprehensively evaluates various sites of peripheral nerve and nerve roots using ultrasound in patients of ALS and obtained consistent results. In previous research studies, the use of few nerves and sites is inadequate and this article is dedicated to improve the comprehensive of study and solve the problem that the previous researches only used a few nerves and several points, and the conclusions are inconsistent.
This result may be explained by the fact that distal axonal degeneration of animal models and patients with ALS [18–21]. The cause of axonal degeneration is unknown, and may involve local axonal damage[20, 22], withdrawal of trophic support from a diseased cell body[23–25], or both. It is increasingly clear that axons are not passive extensions of their parent cell bodies, and may die by mechanisms independent of cell death. However, oxidative stress may play a major role, due to evidence for distal axonal degeneration in SOD1 knockout mice[22, 26], as well as the oxidative damage seen in SOD1 mutant mice and in humans with ALS[20, 27].
The present study also has established that a proximal pattern of atrophy involving the median nerve was evident in ALS patients compared to controls. The reduction of median nerve CSAs were consistent with previous ALS ultrasound studies [4, 8]. A possible explanation for this might be that ALS is a motor neuronopathy, reduced median nerve CSA of the upper arm observed in ALS seems likely to reflect an unusual pattern of predominantly motor axonal loss. The median nerve in the upper arm contains more motor axons that innervate proximal, forearm, and hand muscles compared to the wrist region. The extent of atrophy can be determined in ALS by evaluating the proportion of motor and sensory axons on nerve CSA at each site. In contrast, axons at the wrist and forearm are predominantly sensory. Previous studies revealed that the internal grouping and proportion of motor and sensory branches of the median nerve differs from that of the ulnar nerve[28, 29].
Another possible explantion for the evident median nerve atrophy at proximal in ALS patients is the split hand phenomenon. In ALS patients, hand muscle wasting preferentially affects the ‘thenar (lateral) hand’, including the abductor pollicis brevis (APB) and first dorsal interosseous (FDI) muscles, with relative sparing of the hypothenar muscles (the abductor digiti minimi (ADM)). The mechanisms underlying the split hand are complex and incompletely understood. However, recent evidence suggests that both cortical and spinal/peripheral mechanisms must be involved in the split hand of ALS[30–32]. In 1999, kuwabara and colleagues described a greater reduction of the estimated number of motor units in the APB compared with the ADM[33]. Also, the CMAP ratio of the APB/ADM is reversed in ALS-that is, < 1 instead of > 1, as is normal. Both of these observations indicate preferential involvement of the APB (lateral hand) compared with the ADM (medial hand), typical of split hand.
Another objective of this study was to identify whether the CSAs of peripheral nerve was a sensitive marker to determine the prognosis of ALS. In this study, to ensure the representativeness of the sample, we selected CSAs of median and ulnar nerve in patients with upper limb onset ALS as research object.
The current study shown that ROC-AUC of CSAs were exceed 0.8 in differentiating ALS form healthy controls. However, there was no correlation between CSAs and survival or severity of diseases.
This finding may be explained by the fact that the decrease of peripheral nerve CSA is not pronounced enough to detect the difference between ALS patients with different disability. Schreiber S found that CSA declined at a monthly rate of − 0.04 mm2(forearm) [34]. In conclusion, the findings of this study suggested that peripheral nerves in ALS become progressively thinner, and ultrasound could be sensitive to axonal degeneration.
But the changes of the level of CSA maybe too faint and are not closely related to the severity of diseases and the prognosis.
Larger sample and prospective studies will be needed to confirm these findings. This is an area that should be explored in more detail in future ultrasound studies with additional measurement of individual nerve fascicles to permit more definitive conclusions.