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Article

The Role of Ultrasonography in the Diagnostic Evaluation of Patients with Polyneuropathy

Institute of Clinical Neurophysiology, Division of Neurology, University Medical Center Ljubljana, 1525 Ljubljana, Slovenia
*
Author to whom correspondence should be addressed.
Appl. Sci. 2025, 15(11), 6137; https://doi.org/10.3390/app15116137
Submission received: 28 March 2025 / Revised: 19 May 2025 / Accepted: 26 May 2025 / Published: 29 May 2025
(This article belongs to the Special Issue Applications of Ultrasonic Technology in Biomedical Sciences)

Abstract

Background: The role of ultrasonography (US) in the practical management of polyneuropathies, particularly axonal, remains unclear. The present study aimed to explore the contribution of the US examination of polyneuropathies in daily clinical practice. Methods: We performed a retrospective chart review of patients with clinical and electrophysiological diagnoses of polyneuropathy referred to our US laboratory over eight years. The contribution of US examination in this patient population was evaluated. Results: We analyzed 201 consecutive patients (66% men), aged 12–90 years (mean (SD), 62 (15) years). The most common referral questions were differentiation of hereditary from acquired demyelinating polyneuropathies (71 (35%) patients, sensitivity 63%, specificity 88%), and additional focal neuropathies in patients with generalized neuropathies (51 (25%) patients, sensitivity 75%, specificity 34%). The US examination was pathological in 158 (79%) of patients. The most common US finding was nerve enlargement at typical entrapment sites (73 (36%) patients), followed by proximal nerve thickening (34 (17%) patients). The US provided new diagnoses in 7 (3.5%) patients, contributed to diagnoses in 39 (19%) patients, and confirmed diagnoses in 50 (25%) patients. Conclusion: Our study demonstrated the ability of peripheral nerve US to provide useful additional diagnostic information in about half of the referred 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 mm2 [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 immune-mediated [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-Barré 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 neuroma) 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]. Therefore, the position and indications for US studies in polyneuropathy evaluation protocols are unclear. Nevertheless, the US is gaining recognition as demonstrated by the inclusion of nerve US criteria in the last edition of the European Academy of Neurology Guidelines for diagnosing and treating CIDP [19].
We performed a retrospective chart review of a series of consecutive polyneuropathy patients referred to our neuro-muscular US unit. The primary outcome of our study was the nerve US findings and sensitivity in patients with various polyneuropathies. The secondary outcome was the contribution of nerve US in the diagnosis of common polyneuropathies.

2. Materials and Methods

2.1. Study Design

Our retrospective single-center study included patients referred to the US laboratory at the Institute of Clinical Neurophysiology, University Medical Center Ljubljana, Slovenia from December 2012 to August 2021. Our US unit patients are mainly referred following electrodiagnostic (EDx) examination. We obtained clinical and EDx information from patients’ electronic medical charts. We included patients with ICD-10 diagnoses G60–G64 (i.e., polyneuropathies and other disorders of the peripheral nervous system) and divided them according to their final polyneuropathy diagnoses. Patients referred to as mononeuropathy with additional US findings (e.g., nerve thickening at non-entrapment sites) were further evaluated at our institution. The diagnostic contribution of the US was determined as one of four categories.

2.2. Study Population

We included 209 patients with final diagnosis of polyneuropathy, but excluded 7 patients with motor neuron disease and 1 patient with neurofibromatosis.

2.3. Measures and Evaluation

From the electronic medical charts, we extracted patients’ main demographic and clinical features, including age, sex, EDx, and US findings.

2.4. Primary Outcome Measures

2.4.1. Electrodiagnostic Evaluation (EDx)

EDx examination was performed according to a standard polyneuropathy protocol that includes motor nerve conduction studies (NCS) of the median, ulnar, fibular, and tibial nerves, as well as sensory NCSs of the median, ulnar, and sural nerves, at least unilaterally. Measured NCS parameters included motor and sensory latency, F-wave latency, response duration, response amplitude and area, temporal dispersion, conduction block (at least 30% amplitude reduction), and motor and sensory conduction velocities. These parameters were compared to our laboratory reference values (Table 1). The evaluation protocol also included a needle electromyography (EMG) examination of at least two leg muscles to assess spontaneous denervation activity or reinnervation changes. Based on clinical and EDx criteria for the type of polyneuropathy (Table 2), patients’ diagnoses were divided into: (1) demyelinating polyneuropathy, (2) axonal polyneuropathy, (3) mixed polyneuropathy, and (4) multifocal neuropathy. Several differential diagnostic questions were formulated: (1) demyelinating vs. axonal polyneuropathy, (2) hereditary vs. acquired polyneuropathy, (3) demyelinating vs. diabetic polyneuropathy, (4) MMN vs. motor neuron disease, (5) focal neuropathy superimposed on polyneuropathy, (6) multiple mononeuropathy vs. polyneuropathy, and (7) diagnostic question not clear.

2.4.2. Ultrasonographic Evaluation (US)

All patients were US examined by one of the authors (SP) or a neurophysiological technician, both with >5 years of experience in performing US studies of peripheral nerves at the beginning of the study period. At the time of evaluation, US practitioners were not blinded to findings of clinical and EDx examinations. We used standard US equipment (ProSound Alpha 7), and a 4–13 MHz linear array transducer (Hitachi Aloka Medical, Ltd., Tokyo, Japan).
Our main diagnostic criterion was an increase in the nerve cross-sectional area (CSA) measured by manual tracking of the nerve within the hyperechoic rim of the epineurium while positioning the probe perpendicular to the nerve. Our protocol included US evaluation at standard positions: median and ulnar nerves (at the wrist, forearm, elbow, and upper arm), fibular (at the fibular head and in the popliteal fossa), tibial (at the ankle and in the popliteal fossa) and sural nerve (slightly proximal to the ankle). We used a set of our previously reported reference values for nerve CSA [20] (Table 3). When appropriate, we also described changes in nerve echogenicity, thickening of individual nerve fascicles, segmental nerve thickening, and relevant pathologic structures outside of the peripheral nerves. US impressions were described as: (1) generalized nerve enlargement, (2) proximal nerve enlargements, (3) abnormally thin nerves, (4) nerve thickening in proximal limbs, (5) multifocal nerve enlargement at the non-entrapment sites, (6) multifocal nerve enlargement at the entrapment sites, and (7) normal nerves.
We established the contribution of US examination, based on the US criteria for the type of polyneuropathy (Table 4), to the evaluation of patients as one of the following four categories: (1) US revealed new previously unknown information important for diagnosis; (2) US contributive: enhancing clinical and EDx diagnosis by providing relevant additional information; (3) US confirmative: providing evidence confirming clinical and EDx diagnosis; or (4) US not revealing relevant additional information [21].

2.5. Statistical Analysis

Descriptive statistics were used for the analysis of demographic data. Counts and percentages were provided for categorical variables. Means and standard deviations were calculated for numerical variables. We calculated the sensitivities of US examination in clinical and EDx-confirmed polyneuropathies. Sensitivity was defined as the percentage of patients with clinical and EDx diagnoses of polyneuropathy having pathological US findings compatible with a diagnosis of polyneuropathy.

2.6. Ethic Statements

Due to the retrospective analysis with no direct involvement of patients and data anonymization, the National Ethics Committee of Slovenia waived the necessity of obtaining written informed consent from patients. All analyses were performed by the authors, who were observant to protect all patients’ personal information.

3. Results

3.1. Study Population

During the analyzed period, 201 patients with different polyneuropathies who were 12–90 years old met the inclusion criteria (Table 5).

3.2. Electrodiagnostic (EDx) Evaluation

EDx studies were abnormal in 198 (97%) of our 201 patients with EDx reports available at the time of the US study. The most common EDx diagnoses were axonal polyneuropathy (87 patients, 43%), followed by demyelinating (68 patients, 34%) and mixed polyneuropathy (23 patients, 11%; Figure 1). The most common final etiological diagnosis was diabetic polyneuropathy, followed by hereditary polyneuropathy (Table 5).

3.3. Ultrasonography

US examination was abnormal in 158 (79%) of our patients but varied according to the etiology of polyneuropathy and referral questions. Figure 1 shows the frequency of different US findings in our patient population. The most common referral questions for US examination were differentiation of hereditary from acquired demyelinating polyneuropathies (71 patients) and demonstration of additional focal neuropathies in patients with generalized polyneuropathies (51 patients; Figure 1). The sensitivity and specificity for distinguishing hereditary from acquired polyneuropathies were 63% and 88%, respectively, while demonstration of additional focal neuropathies had a sensitivity of 75% and a specificity of 34%. The US provided a new diagnosis in 7 (3%) patients (Table 6), was contributive in 39 (19%) patients, and confirmatory in 50 (25%) of the included patients, but did not provide additional diagnostic information in 105 (52%) patients.

3.4. Relation of US to EDx

In our cohort, the most common EDx diagnosis was axonal polyneuropathy (Figure 1), with the most common referral question of superimposed focal neuropathies (35 patients). The most common US finding in this referral group was nerve thickening at the entrapment sites (16 patients), followed by normal findings (8 patients), single focal thickening at the non-entrapment site (5 patients), uniform nerve thickening (5 patients), and proximal nerve thickening (2 patients). Another common referral question in this group was a differentiation of hereditary from acquired polyneuropathy (32 patients), and we most often found normal findings (14 patients), followed by nerve thickening on entrapment sites (10 patients).
Patients with EDx diagnosis of demyelinating polyneuropathies were the second most common, with referral physicians most often trying to differentiate hereditary from acquired forms (59 patients). In this referral group, we also most often found nerve thickening at entrapment sites (20 patients), followed by proximal nerve thickening (13 patients), uniform nerve thickening (11 patients), and nerve thickening at non-entrapment sites (10 patients).
A much less common group of referrals were patients with EDx mixed polyneuropathies, and in these patients, referral physicians most often looked for differentiation between demyelinating and axonal forms (10 patients). In this group, we found proximal nerve thickening (3 patients) and uniform thickening typical for hereditary demyelinating polyneuropathies (1 patient). Another common referral question in this population was to differentiate hereditary from acquired demyelinating polyneuropathy (8 patients).
In patients with EDx multifocal neuropathies, referral physicians tried to differentiate hereditary from acquired demyelinating polyneuropathy (4 patients) and MMN from ALS (1 patient).

4. Discussion

In this retrospective chart review, we explored the role of the US in the diagnostic evaluation of patients with EDx-confirmed polyneuropathy. Most patients in our polyneuropathy cohort were referred to the US to improve their diagnostic formulation as obtained by clinical and EDx examination. US complements the EDx examination by providing precise anatomical location and information on the etiology of the nerve lesion, thereby increasing sensitivity. The US was first used in routine clinical practice for diagnosing focal mononeuropathies, such as median entrapment neuropathy at the wrist (i.e., carpal tunnel syndrome) and ulnar neuropathy. In the former, it is also used to guide therapeutic injections. In the latter, it is important in differentiating the cubital tunnel entrapment and the retrocondylar compression, which determines treatment [22,23]. Later, it became clear that the US can also help in diagnosing polyneuropathies, particularly demyelinating, and the detection of focal neuropathies superimposed on generalized polyneuropathies. In our population, with a large majority (98%) of patients with abnormal EDx findings, the sensitivity of the US examination was moderate (64%). Sensitivity was found to be higher in patients with typical and multifocal CIDP, with uniform and proximal nerve thickening in the former and segmental nerve enlargement at non-entrapment sites in the latter. These findings are consistent with the literature and support the pathophysiology of segmental inflammation in both diseases [8,9]. The sensitivity of the US in hereditary polyneuropathy was lower compared to the literature [9,10]. This can be explained by the inclusion of other types of CMT, not only CMT 1A. The frequent diagnosis in this cohort was also hereditary neuropathy with liability to pressure palsies (HNPP). In that condition, nerve enlargement is less pronounced and frequent at the entrapment sites [7]. The sensitivity in diabetic polyneuropathy was similar to that reported in the literature. In this condition, nerve US generally shows normal or slightly enlarged nerves, particularly the proximal median and tibial nerve segments [10]. Sensitivity was lowest in idiopathic polyneuropathy, where focal nerve thickening at entrapment and non-entrapment sites was the most common finding.
The US provided a novel diagnosis in 7 (3%) of our patients, including 2 patients with unexpected findings of peripheral nerve tumors reported elsewhere [24]. We also found nerve thickening at non-entrapment sites typical of focal demyelinating polyneuropathy in a patient with EDx findings typical of axonal polyneuropathy, a finding reported also by others [25]. This is useful in cases where EDx studies are unable to provide exact anatomical location.
The US was regarded as contributive in 39 (19%) of our patients by providing information on the nerve size and structures outside the nerves. This is particularly important in patients with polyneuropathy and superimposed focal neuropathy (e.g., patients with diabetic polyneuropathy and suspected median entrapment neuropathy at the wrist). Focal nerve thickening was also found in several patients with amyloid polyneuropathy [20], other metabolic (uremic, vitamin B12 deficiency), autoimmune (rheumatoid arthritis) polyneuropathies, and polyneuropathy of unclear etiology. 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 vasculitic, 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. Nevertheless, as in clinical practice, we performed US studies at the time of patient referral.

5. Conclusions

This retrospective analysis confirmed the utility of the US in the diagnostic evaluation of patients with different forms of polyneuropathy and also in routine clinical practice. Although the US only rarely provided a new diagnosis, in many patients with polyneuropathy US either contributed to or at least confirmed the diagnosis. The US was most useful in patients with well-formulated and meaningful referral questions.

Author Contributions

Conceptualization, S.P.; methodology, S.P.; validation, M.J.; formal analysis, M.J.; data curation, M.J.; writing—original draft preparation, M.J.; writing—review and editing, S.P.; visualization, M.J.; supervision, S.P.; funding acquisition, S.P. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by The Slovenian Research and Innovation Agency, grant number P3-0338.

Institutional Review Board Statement

Ethical review and approval were waived for this study due to the retrospective analysis with no direct involvement of patients and data anonymization.

Informed Consent Statement

Patient consent was waived due to the retrospective analysis with no direct involvement of patients.

Data Availability Statement

The authors will make the raw data supporting this article’s conclusions available upon request.

Acknowledgments

The authors thank Gregor Omejec, for his help during peripheral nerve ultrasonography.

Conflicts of Interest

The authors declare no conflicts of interest. The funders had no role in the study’s design; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Abbreviations

The following abbreviations are used in this manuscript:
ALSAmyotrophic lateral sclerosis
CIDPChronic inflammatory demyelinating polyneuropathy
CMT1ACharcot-Marie-Tooth disease type 1A
DADSDistal acquired demyelinating symmetric polyneuropathy
EDxElectrodiagnosis
MMNMultifocal motor neuropathy
TTRTransthyretin
USUltrasonography

References

  1. Suk, J.I.; Walker, F.O.; Cartwright, M.S. Ultrasonography of peripheral nerves. Curr. Neurol. Neurosci. Rep. 2013, 13, 328. [Google Scholar] [CrossRef]
  2. Walker, F.; Cartwright, M.S. Neuromuscular Ultrasound; Elsevier, Saunders: Philadelphia, PA, USA, 2011; pp. 1–200. [Google Scholar]
  3. Buchberger, W.; Schön, G.; Strasser, K.; Jungwirth, W. High-resolution ultrasonography of the carpal tunnel. J. Ultrasound Med. 1991, 10, 531–537. [Google Scholar] [CrossRef]
  4. Kerasnoudis, A.; Tsivgoulis, G. Nerve Ultrasound in Peripheral Neuropathies: A Review. J. Neuroimaging 2015, 25, 528–538. [Google Scholar] [CrossRef]
  5. Lugao, H.B.; Nogueira-Barbosa, M.H.; Marques, W., Jr.; Foss, N.T.; Frade, M.A. Asymmetric Nerve Enlargement: A Characteristic of Leprosy Neuropathy Demonstrated by Ultrasonography. PLoS Negl. Trop. Dis. 2015, 9, e0004276. [Google Scholar] [CrossRef]
  6. Zaidman, C.M.; Al-Lozi, M.; Pestronk, A. Peripheral nerve size in normals and patients with polyneuropathy: An ultrasound study. Muscle Nerve 2009, 40, 960–966. [Google Scholar] [CrossRef]
  7. Zaidman, C.M.; Harms, M.B.; Pestronk, A. Ultrasound of inherited vs. acquired demyelinating polyneuropathies. J. Neurol. 2013, 260, 3115–3121. [Google Scholar] [CrossRef]
  8. Beekman, R.; van den Berg, L.H.; Franssen, H.; Visser, L.H.; van Asseldonk, J.T.; Wokke, J.H. Ultrasonography shows extensive nerve enlargements in multifocal motor neuropathy. Neurology 2005, 65, 305–307. [Google Scholar] [CrossRef]
  9. Grimm, A.; Vittore, D.; Schubert, V.; Lipski, C.; Heiling, B.; Decard, B.F.; Axer, H. Ultrasound pattern sum score, homogeneity score and regional nerve enlargement index for differentiation of demyelinating inflammatory and hereditary neuropathies. Clin. Neurophysiol. 2016, 127, 2618–2624. [Google Scholar] [CrossRef]
  10. Telleman, J.A.; Herraets, I.J.; Goedee, H.S.; van Asseldonk, J.T.; Visser, L.H. Ultrasound scanning in the diagnosis of peripheral neuropathies. Pract. Neurol. 2021, 21, 186–195. [Google Scholar] [CrossRef]
  11. Grimm, A.; Décard, B.F.; Schramm, A.; Pröbstel, A.K.; Rasenack, M.; Axer, H.; Fuhr, P. Ultrasound and electrophysiologic findings in patients with Guillain-Barré syndrome at disease onset and over a period of six months. Clin. Neurophysiol. 2016, 127, 1657–1663. [Google Scholar] [CrossRef]
  12. Grimm, A.; Décard, B.F.; Athanasopoulou, I.; Schweikert, K.; Sinnreich, M.; Axer, H. Nerve ultrasound for differentiation between amyotrophic lateral sclerosis and multifocal motor neuropathy. J. Neurol. 2015, 262, 870–880. [Google Scholar] [CrossRef] [PubMed]
  13. Kerasnoudis, A.; Pitarokoili, K.; Haghikia, A.; Gold, R.; Yoon, M.S. Nerve ultrasound protocol in differentiating chronic immune-mediated neuropathies. Muscle Nerve 2016, 54, 864–871. [Google Scholar] [CrossRef] [PubMed]
  14. Grimm, A.; Decard, B.F.; Axer, H.; Fuhr, P. The Ultrasound pattern sum score—UPSS. A new method to differentiate acute and subacute neuropathies using ultrasound of the peripheral nerves. Clin. Neurophysiol. 2015, 126, 2216–2225. [Google Scholar] [CrossRef]
  15. Haffey, P.R.; Bansal, N.; Kaye, E.; Ottestad, E.; Aiyer, R.; Noori, S.; Gulati, A. The Regenerative Potential of Therapeutic Ultrasound on Neural Tissue: A Pragmatic Review. Pain Med. 2020, 21, 1494–1506. [Google Scholar] [CrossRef]
  16. di Biase, L.; Falato, E.; Caminiti, M.L.; Pecoraro, P.M.; Narducci, F.; Di Lazzaro, V. Focused Ultrasound (FUS) for Chronic Pain Management: Approved and Potential Applications. Neurol. Res. Int. 2021, 2021, 8438498. [Google Scholar] [CrossRef]
  17. Phenix, C.P.; Togtema, M.; Pichardo, S.; Zehbe, I.; Curiel, L. High intensity focused ultrasound technology, its scope and applications in therapy and drug delivery. J. Pharm. Pharm. Sci. 2014, 17, 136–153. [Google Scholar] [CrossRef] [PubMed]
  18. Padua, L.; Aprile, I.; Pazzaglia, C.; Frasca, G.; Caliandro, P.; Tonali, P.; Martinoli, C. Contribution of ultrasound in a neurophysiological lab in diagnosing nerve impairment: A one-year systematic assessment. Clin. Neurophysiol. 2007, 118, 1410–1416. [Google Scholar] [CrossRef]
  19. Van den Bergh, P.Y.K.; van Doorn, P.A. European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint Task Force-Second revision. Eur. J. Neurol. 2021, 28, 3556–3583. [Google Scholar] [CrossRef]
  20. Podnar, S.; Sarafov, S.; Tournev, I.; Omejec, G.; Zidar, J. Peripheral nerve ultrasonography in patients with transthyretin amyloidosis. Clin. Neurophysiol. 2017, 128, 505–511. [Google Scholar] [CrossRef]
  21. Padua, L.; Liotta, G.; Di Pasquale, A.; Granata, G.; Pazzaglia, C.; Caliandro, P.; Martinoli, C. Contribution of ultrasound in the assessment of nerve diseases. Eur. J. Neurol. 2012, 19, 47–54. [Google Scholar] [CrossRef]
  22. Omejec, G.; Podnar, S. Utility of nerve conduction studies and ultrasonography in ulnar neuropathies at the elbow of different severity. Clin. Neurophysiol. 2020, 131, 1672–1677. [Google Scholar] [CrossRef]
  23. Omejec, G.; Žgur, T.; Podnar, S. Diagnostic accuracy of ultrasonographic and nerve conduction studies in ulnar neuropathy at the elbow. Clin. Neurophysiol. 2015, 126, 1797–1804. [Google Scholar] [CrossRef]
  24. Podnar, S. Ultrasonography of peripheral nerve tumours: A case series. Radiol. Oncol. 2023, 57, 35–41. [Google Scholar] [CrossRef]
  25. Herraets, I.J.T.; Goedee, H.S.; Telleman, J.A.; van Eijk, R.P.A.; van Asseldonk, J.T.; Visser, L.H.; van den Berg, L.H.; van der Pol, W.L. Nerve ultrasound improves detection of treatment-responsive chronic inflammatory neuropathies. Neurology 2020, 94, e1470–e1479. [Google Scholar] [CrossRef]
  26. Li, Y.; Niu, J.; Liu, T.; Ding, Q.; Wu, S.; Guan, Y.; Cui, L.; Liu, M. Conduction Block and Nerve Cross-Sectional Area in Multifocal Motor Neuropathy. Front. Neurol. 2019, 10, 1055. [Google Scholar] [CrossRef]
  27. Rajabally, Y.A.; Stettner, M.; Kieseier, B.C.; Hartung, H.P.; Malik, R.A. CIDP and other inflammatory neuropathies in diabetes—Diagnosis and management. Nat. Rev. Neurol. 2017, 13, 599–611. [Google Scholar] [CrossRef]
  28. Breiner, A.; Ebadi, H.; Bril, V.; Barnett, C.; Katzberg, H.D. Ultrasound in Multifocal Motor Neuropathy: Clinical and Electrophysiological Correlations. J. Clin. Neuromuscul. Dis. 2019, 20, 165–172. [Google Scholar] [CrossRef]
  29. Feldman, E.L.; Callaghan, B.C.; Pop-Busui, R.; Zochodne, D.W.; Wright, D.E.; Bennett, D.L.; Bril, V.; Russell, J.W.; Viswanathan, V. Diabetic neuropathy. Nat. Rev. Dis. Primers 2019, 5, 42. [Google Scholar] [CrossRef] [PubMed]
  30. Podnar, S. Ultrasonographic abnormalities in clinically unaffected nerves of patients with non-vasculitic motor and sensorimotor mononeuropathies. Muscle Nerve 2024, 70, 766–773. [Google Scholar] [PubMed]
Figure 1. The most common and clinically relevant pathways of patients with polyneuropathy through our diagnostic evaluation. Numbers describe patient numbers. Several US findings may be demonstrated in individual patients. ALS—amyotrophic lateral sclerosis; EDx—electrodiagnostics; MMN—multifocal motor neuropathy; US—ultrasonography.
Figure 1. The most common and clinically relevant pathways of patients with polyneuropathy through our diagnostic evaluation. Numbers describe patient numbers. Several US findings may be demonstrated in individual patients. ALS—amyotrophic lateral sclerosis; EDx—electrodiagnostics; MMN—multifocal motor neuropathy; US—ultrasonography.
Applsci 15 06137 g001
Table 1. EDx reference values for the main motor and sensory nerves used in the present study.
Table 1. EDx reference values for the main motor and sensory nerves used in the present study.
NerveLatency (ms)Amplitude
(mV/uV)
Velocity (m/s)F-Wave Latency (ms)
Motor
 Median<4.4>4.0>49<31
 Ulnar<3.3>6.0>49<32
 Radial<2.9>2.0>49
 Fibular<6.5>2.0>44<56
 Tibial<5.8>4.0>41<56
Sensory
 Median >20>50
 Ulnar >17>50
 Radial >15>50
 Sural >6>40
 Medial plantar >2>35
Table 2. Electrodiagnostic (EDx) criteria for different types of polyneuropathies evaluated in the study.
Table 2. Electrodiagnostic (EDx) criteria for different types of polyneuropathies evaluated in the study.
PolyneuropathyEDx Criteria
Demyelinating
-
Distal motor latency ≥ 50% above ULN in 2 nerves
-
Motor conduction velocity < 70% of LLN in 2 nerves
-
F-wave latency ≥ 20% above ULN in 2 nerves
-
Motor conduction block ≥ 30%
-
Abnormal CMAP temporal dispersion: >30% duration increase
-
Sensory nerve conduction velocity < 80% of LLN
Axonal
-
CMAP amplitude < 80% of LLN in 2 nerves
-
Normal or slightly reduced conduction velocity
-
SNAP amplitude < 80% below LLN in 2 nerves
-
Reduced motor unit recruitment on needle EMG
-
Spontaneous denervation activity on needle EMG
Mixed
-
Combined features of axonal and demyelinating polyneuropathy
Multifocal
-
Motor conduction block ≥ 30% at non-entrapment sites in >2 nerves
-
Asymmetric segmental demyelination
-
Chronic neurogenic changes on needle EMG
CMAP—Compound Muscle Action Potential; EDx—electrodiagnostic, EMG—electromyography; LLN—the lower limit of normal; SNAP—Sensory Nerve Action Potential; ULN—the upper limit of normal.
Table 3. The upper reference values for the cross-sectional area (CSA) of the main limb nerves used in the present study.
Table 3. The upper reference values for the cross-sectional area (CSA) of the main limb nerves used in the present study.
Nerve and SiteCSA (mm²)
Median
 Wrist<12
 Forearm<10
 Antecubital fossa<12
 Upper arm<13
Ulnar
 Wrist<8
 Forearm<9
 Elbow<11
 Upper arm<9
Fibular
 Fibular head<14
 Popliteal fossa<9
Tibial
 Ankle<18
 Popliteal fossa<39
Sciatic<46
Sural<4
Table 4. US criteria for the type of polyneuropathy.
Table 4. US criteria for the type of polyneuropathy.
PolyneuropathyUS Criteria
Diabetic
-
Variable, often mild-moderate diffuse nerve enlargements (2.5 SD CSA) pronounced in median and tibial nerves
Hereditary
-
Uniform symmetric nerve enlargements (>2.5 SD CSA)
Idiopathic
-
Variable, often mild-moderate diffuse nerve enlargements (1.5 SD CSA)
Typical CIDP
-
Uniform often symmetric nerve enlargement (>2.5 SD CSA)
DADS
-
Uniform symmetric nerve enlargement (>2.5 SD CSA)
Multifocal CIDP
-
Multifocal asymmetric nerve enlargements (>2.0 SD CSA)
MMN
-
Multifocal or segmental nerve enlargements at non-entrapment sites in at least one nerve
Multiple
mononeuropathy
-
Moderate asymmetric nerve enlargements (>1.5 SD CSA)
Paraproteinemic polyneuropathy
-
Mild, often asymmetric nerve enlargements (>1.0 SD CSA)
Amyloid polyneuropathy
-
Marked nerve thickening with hypoechoic appearance (>2.5 SD CSA)
Table 5. Demographics and sensitivity of peripheral nerve ultrasonography (US) in a series of 201 consecutive patients with various polyneuropathies.
Table 5. Demographics and sensitivity of peripheral nerve ultrasonography (US) in a series of 201 consecutive patients with various polyneuropathies.
DiagnosisNumber
(%)
Mean Age (y)
(SD)
Males
(%)
US Sensitivity (%)
Final cohort201 (100%)62 (15)6664
Diabetic polyneuropathy38 (19%)66 (12)8260
Hereditary polyneuropathy35 (17%)52 (17)4963
Idiopathic polyneuropathy 28 (14%)67 (14)7528
Typical CIDP 22 (11%)62 (19)4182
DADS12 (6%)74 (6)9258
Multifocal CIDP11 (5.5%)56 (12)9191
MMN8 (4%)62 (14)5063
Multiple mononeuropathy7 (3.5%)60 (20)2957
Paraproteinemic polyneuropathy5 (2.5%)70 (6)8060
TTR amyloid polyneuropathy4 (2%)60 (7)5075
CIDP—chronic inflammatory demyelinating polyneuropathy; DADS—distal acquired demyelinating symmetric polyneuropathy; MMN—multifocal motor neuropathy; TTR—transthyretin.
Table 6. Findings in 7 patients with new diagnoses revealed by peripheral nerve ultrasonography (US).
Table 6. Findings in 7 patients with new diagnoses revealed by peripheral nerve ultrasonography (US).
FindingsNumberReferral Diagnosis/Comment
Demyelinating polyneuropathy1tarsal tunnel syndrome
Expansive lesions2hereditary polyneuropathy
Multifocal CIDP2typical CIDP and MGUS
Thoracic outlet syndrome1radiation plexopathy
Proximal nerve enlargement1small fiber neuropathy
CIDP—chronic inflammatory demyelinating polyneuropathy; MGUS—monoclonal gammopathy of undetermined significance.
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Jožef, M.; Podnar, S. The Role of Ultrasonography in the Diagnostic Evaluation of Patients with Polyneuropathy. Appl. Sci. 2025, 15, 6137. https://doi.org/10.3390/app15116137

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Jožef M, Podnar S. The Role of Ultrasonography in the Diagnostic Evaluation of Patients with Polyneuropathy. Applied Sciences. 2025; 15(11):6137. https://doi.org/10.3390/app15116137

Chicago/Turabian Style

Jožef, Maj, and Simon Podnar. 2025. "The Role of Ultrasonography in the Diagnostic Evaluation of Patients with Polyneuropathy" Applied Sciences 15, no. 11: 6137. https://doi.org/10.3390/app15116137

APA Style

Jožef, M., & Podnar, S. (2025). The Role of Ultrasonography in the Diagnostic Evaluation of Patients with Polyneuropathy. Applied Sciences, 15(11), 6137. https://doi.org/10.3390/app15116137

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