# The Role of Ultrasonography in the Diagnostic Evaluation of Patients with Polyneuropathy
## 4 Discussion
In MMN and multifocal CIDP arm nerves were characteristically thickened at non-entrapment sites, often without concomitant conduction block on EDx, as reported before [26]. On the other hand, we found nerve thinning in 3 patients with multifocal inflammatory neuropathies (MMN and multifocal CIDP), probably due to secondary axonal loss in the advanced disease stage [18]. The US was confirmative in 50 (25%) of our patients, which increased our confidence in clinical and EDx diagnosis. The high sensitivity of US in CIDP with its well-recognized non-uniform generalized nerve thickening is not unexpected [9]. Together with proximal, particularly tibial and median nerve thickening found in subacute diabetic polyneuropathies [10], this helped us to diagnose superimposed CIDP in patients with diabetes, which is a common and clinically relevant diagnostic dilemma [19; 27]. The proximal median nerve segment is commonly swollen also in several other polyneuropathies, including vasculitis, and transthyretin (TTR) amyloid polyneuropathy [20]. In the remaining 52% of patients US did not provide relevant additional information. This occurred mainly in patients with idiopathic polyneuropathy, probable hereditary axonal polyneuropathies (CMT2), and in a minority of patients with diabetic polyneuropathy. These patients had predominantly normal US studies or incidental abnormalities, as reported previously. The majority of acquired and hereditary axonal polyneuropathies have normal or only slightly enlarged nerves [28]. The high frequency of diabetic polyneuropathy in our study cohort is not surprising, as diabetes is the most common cause of polyneuropathy worldwide [29]. By contrast, in our study cohort, hereditary polyneuropathies were probably overrepresented, mainly due to the well-known ability of the US to demonstrate uniform nerve thickening in patients with demyelinating forms [9]. Referral for additional focal neuropathy in patients with generalized polyneuropathy is clinically very useful due to US high sensitivity. By contrast, EDx has higher specificity. Differentiation between inherited and acquired demyelinating polyneuropathies is also useful, and US has high sensitivity and specificity, allowing the exclusion of hereditary demyelinating polyneuropathies. Patients with multifocal CIDP showed the highest US sensitivity and specificity and thus benefited the most. They typically had moderate diffuse nerve enlargement with superimposed focal nerve thickening on non-entrapment sites. The main strength of this study is the evaluation of the relationship between EDx and US findings in the context of differential diagnosis. This provides additional insight into the complementary role of US and EDx in the diagnosis of polyneuropathy. Calculation of the sensitivity confirmed this important complementary role, especially in hereditary and acquired demyelinating polyneuropathies. In clinical practice, the increased sensitivity allows us to detect not only EDx silent conduction blocks [24] but also segmental nerve thickening in asymptomatic nerves [30]. The present study has several limitations. The most important is its retrospective design, which precluded the standardization of the obtained information. As a consequence, we were not able to provide an objective quantitative assessment of the contribution of the US to patient management. Furthermore, investigators performing US were not blinded to the findings of the neurologic examination and EDx testing. This might introduced certain bias in the evaluation, but on the other side modelled the usual clinical evaluation. US imaging is also dependent on the operator's skill and experience. However, in the present study, we relied mainly on robust parameters of nerve CSAs determined on standard measuring points. Therefore, we do not believe that the operator's skill and experience presented a major issue in the evaluation of major limb nerves. CSA may change throughout the course of the disease, but the study design did not enable us to explore CSA changes over time.