The primary objective of this study is to assess the neuro-sonography for diagnosis and differentiation of amyotrophic lateral sclerosis. This is a conventional case–control study conducted on 90 patients attending to Ain-Shams University Hospitals.
To our knowledge, this is the first comparative neuro-sonography study to assess differentiation of ALS and cervical degeneration subjects presented with similar clinical picture.
In our study, we also worked on the neuro-sonography cross-sectional area of both lower limbs’ peripheral nerves in addition to both upper limbs, which is scarcely preceded by other studies.
Peripheral nerve atrophy as reported on group-level in most of the ultrasound studies comparing ALS and healthy controls most likely reflects axonal degeneration in ALS, but correlation studies between ultrasound and histopathology are thus far lacking.
Our findings goes in accordance with other authors who also found out that ALS could be prevalent in specific age group with specific subtypes and gender; ALS is characterized by a sexual dimorphism, the most obvious being the higher risk of developing the disease in men [7]. More subtle differences between the two sexes have been reported both in ALS preclinical models and in humans [8].
Age is the strongest risk factor of ALS as found out by [7], 8]. It has been found out that the median age at onset is 67.1 years, Bulbar phenotype was correlated with older age, where women were more affected than men at increasing ages, while classic phenotype, on the contrary, was associated with younger age, where the risk in men increased with age, PUMN was correlated with younger age, flail arm phenotype was associated with male sex and less strongly with younger age and finally, respiratory phenotype was correlated with male sex and showed a trend toward a higher frequency in older age [9].
The spread of lesions across the CNS in ALS has been explained either as a neuroanatomical contiguous propagation in the upper and lower motor neurons, with random onset in discrete body regions [10] or as a prion-like propagation, with either contiguous or noncontiguous diffusion [11] or, finally, as a sequential pattern of spread of TDP43 pathology with a corticofugal mechanism [12].
Further aspects that have contributed to the large variance of the available nerve ultrasound data include the lack of standardized imaging protocols and ratings.
In our study, we compared our results to normal values reported by [13] that the mean median nerve CSAs ± SD at the distal wrist crease was 7.2 ± 1 mm2; mid-forearm 4.8 ± 0.9 mm2; mid-arm 6.1 ± 1 mm2; axilla 5.9 ± 0.9 mm2, while average ulnar nerve CSAs distal wrist crease, 5.9 mm2; arterial split, 6.3 mm2; 2 cm distal to tip of the medial epicondyle, 6.4 mm2; tip of the medial epicondyle, 6.5 mm2; 2 cm proximal to tip of the medial epicondyle, 6.7 mm2; mid-humerus, 6.1 mm2; and axilla, 6.2 mm2, as reported by [14].
The mean cross-sectional areas of the radial nerves reported by [15] were as follows: at 4 cm at the lateral epicondyle of the humerus (4 cm), 5.14 ± 1.24 mm2; and at mid-humerus (midpoint between the elbow crease and axilla), 5.08 ± 1.23 mm2
Regarding tibial nerve at the popliteal fossa 19 mm2 ± 6.9, tibial nerve at the level of the medial malleolus 12.7 mm2 ± 4.5, common peroneal nerve at the popliteal fossa 9.5 mm2 ± 4, common peroneal nerve fibular head 8.9 mm2 ± 3.2, sural nerve 3.5 mm2 ± 1.4 [16].
Schreiber et al., compared nerve CSA between ALS and controls, similarly reporting peripheral nerve atrophy in ALS affecting the ulnar nerve at the wrist, the median nerve at the forearm, and the ulnar, median and radial nerves in the upper arm [17].
However, not all studies are in agreement on which nerves are reduced at which sites. One group reported pronounced atrophy of the distal ulnar nerve [18]; Noto et al. did not find a reduction of ulnar nerve size in ALS [19]
Mori et al., also found that the cervical root and peripheral nerve CSA atrophy seem thereby to occur in all ALS disease phenotypes independent of the degree of UMN or LMN involvement or from the site of disease onset [20].
It was proposed that CSA enlargement of the four nerves yielded an optimal combined sensitivity and specificity to discriminate between ALS and MMN. Goedee et al. later stated that
CSA enlargement of even just two nerves should be accurate enough to distinguish between the two diseases [21].
The total neuro-sonography score at a cut-off point (≤127) predicted patients with ALS with good (85%) accuracy, sensitivity of 73% and specificity of 83% (p < 0.01). This shows the significance of neuro-sonography as a diagnostic and differentiation tool in neurodegenerative diseases and neuromuscular diseases as well, and this goes in agreement with other authors such as [22], who found out that the cross-sectional area of the median nerve in the mid-arm was smaller in the ALS group than controls (10.5 mm2 vs 12.7 mm2, p = 0.0023). This also goes in accordance with [18] who found out that compared with controls, ALS patients had significant, distally pronounced reductions of ulnar CSA (forearm/wrist level) across all disease groups, except for PLS and median nerve CSA (forearm/wrist level) did not differ between controls and ALS while ulnar nerve ultrasound in ALS subgroups revealed significant differences in distal CSA values, which suggests it has value as a marker of LMN involvement. Its potential was particularly evident in the UMND and PLS groups, which can be hard to separate clinically.
