# The Role of Ultrasonography in the Diagnostic Evaluation of Patients with Polyneuropathy
## 1 Introduction  
Clinical features supported by nerve conduction studies (NCS) and needle electromyography (EMG) remain a cornerstone in managing polyneuropathies. However, clinical and NCS criteria are complex and invasive, focusing primarily on specificity. For example, NCSs require limb temperature control, whereas needle EMG requires patient tolerance and is subject to sampling bias. Misinterpretation and misdiagnosis are common, resulting in the exclusion of patients who could benefit from treatment, for example, in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). Therefore, more sensitive, practical, and non-invasive diagnostic tools are needed in clinical settings. Nerve ultrasound (US) is a relatively novel non-invasive diagnostic tool for evaluating nerves, particularly superficial ones. Nerves are recognized by hypoechogenic fascicles, encircled by hyperechogenic fibrous tissue, i.e., a honeycomb structure. The most relevant US features are echogenicity and nerve size. The latter is assessed in the transverse plane and expressed as the cross-sectional area (CSA) in mm\({}^{2}\)[1]. With advancements in US technology, a detailed localization, morphological, and etiological evaluation of peripheral nerves has become possible [1,2]. Initially, the complementary role of nerve US was recognized in focal compression and entrapment mononeuropathies [3]. In clinical practice, US is commonly used in the diagnosis of carpal tunnel syndrome (CTS) and ulnar neuropathy (UNE). Later, the diagnostic potential of nerve US was also shown in polyneuropathies, particularly demyelinating [4], either immunmediated [5], hereditary [6], or infectious [5]. Typical US findings in polyneuropathies include marked uniform nerve enlargement in Charcot-Marie-Tooth disease type 1A (CMT1A), whereas other CMT types have mild uniform nerve enlargement, more pronounced at entrapment sites. In chronic inflammatory demyelinating polyneuropathy (CIDP), nerve enlargement is less pronounced and uniform, expressed particularly in proximal nerve segments [7]. By contrast, segmental nerve enlargement is typical of multifocal motor neuropathy (MMN) [8] and multifocal CIDP [9]. In contrast, the most common axonal polyneuropathies usually have normal US findings or mild to moderate nerve enlargement [10]. Nerve US is useful in Guillain-Barre syndrome (GBS) showing particularly proximal nerve enlargement in the acute phase, 1-3 days after the onset of symptoms and before the appearance of NCS abnormalities [11]. Nerve enlargement may persist after the symptoms are resolved, or nerves may even become thinner. The US can also help to distinguish MMN from amyotrophic lateral sclerosis (ALS) by detecting multifocal nerve enlargements in the former [12]. Several US protocols and scoring systems have been proposed for use in polyneuropathies, ranging from short and simple [13] to more extensive and complex [14]. The former includes the quantification of the pattern and extent of nerve enlargement, such as intra- and inter-nerve variability between two nerves, while the latter includes the location and the degree of nerve enlargement between both sides as well. In addition to its diagnostic value, nerve US also has therapeutic applications. Low Intensity Pulsed Ultrasound (LIPUS) promotes nerve regeneration by stimulating Schwann cells and axonal growth, particularly in sciatic or facial nerve injuries. It is also used for neuromodulation in the treatment of neuropathic pain [15]. High Intensity Focused Ultrasound (HIFUS) is used for non-invasive nerve ablation in the treatment of chronic pain (trigeminal neuralgia, Morton's neuromons) using thermal and mechanical signals to disrupt pain transmission [16]. Phonophoresis is used to enhance the transdermal delivery of medications (corticosteroids, lidocaine) in the treatment of neural inflammation [17]. However, the actual contribution of the US in the daily diagnosis and management of patients with polyneuropathies has been only rarely studied [18].