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This article presents a protocol for nerve ultrasound in polyneuropathies to aid the diagnosis of inflammatory neuropathies.
Nerve ultrasound is increasingly used in the differential diagnosis of polyneuropathy as a complementary tool to nerve conduction studies. Morphological alterations of the peripheral nerves, such as increasing the cross-sectional area (CSA), have been described in various immune-mediated polyneuropathies. The most prominent morphological changes in nerve ultrasound have been described for the chronic inflammatory demyelinating polyneuropathy (CIDP)-spectrum disease. CIDP may be distinguished from hereditary and other polyneuropathies by measuring the extent and pattern of nerve swellings (CSA increase). Typical findings in demyelinating inflammatory neuropathies are multifocal nerve swellings with inhomogeneous fascicular structure, while CSA increase in demyelinating hereditary neuropathies occurs in a more generalized and homogenous manner. In other non-inflammatory axonal neuropathies, nerves can appear with normal or slight CSA increases, especially in typical entrapment sites. This article presents technical requirements for nerve ultrasound, an examination procedure using a standardized examination protocol, current reference values for the CSA, and typical sonographic pathological findings in patients with inflammatory neuropathies.
Next to clinical examination, evaluating any large-fiber polyneuropathy includes an electrophysiological examination to characterize the motor or sensory system's involvement and differentiate axonal from demyelinating damage1. In axonal polyneuropathy, toxic and diabetic neuropathy are the leading causes, while in demyelinating polyneuropathies, hereditary or inflammatory neuropathies such as CIDP should be considered2,3,4. Commonly used diagnostic criteria for CIDP are the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria established in 2005 and revised in 2010 and 20215. These define clinical and electrophysiological criteria to diagnose CIDP and describe additional criteria such as nerve biopsy to detect demyelination or inflammation. However, in some cases, despite a thorough diagnostic workup, the cause of neuropathy remains ambiguous. In these cases, nerve ultrasound offers a complementary method to examine the nerves not functionally but morphologically6. Several studies proved the use of nerve ultrasound as an additional tool in diagnosing CIDP, so that the 2021 revised EFNS/PNS criteria implemented nerve ultrasound in the guideline5. The advantage of nerve ultrasound compared to other imaging methods such as magnet resonance neurography (MRN) is that it can be used directly by the treating neurologists as a bedside tool; it is relatively cost-efficient. It can be used repeatedly, as it is noninvasive and not painful.
Typical characteristics of CIDP observed in nerve ultrasound are cross-sectional-area (CSA) increase7,8, also found in hereditary polyneuropathies. In CIDP, this affects individual nerve segments heterogeneously7,9.
A variety of examination protocols have been published10,11,12,13,14,15 trying to clarify normal CSA values and determine the adequate anatomical positions of ultrasound examination. Some of these positions are similar in most examination protocols. However, a widely accepted protocol to standardize the examination process and simplify the interpretation of the measurements does not exist.
This article demonstrates the nerve ultrasound examination using a standardized protocol for polyneuropathies, presents various reference values for the CSA, and shows typical pathological findings in patients with inflammatory neuropathies.
Technical requirements for nerve ultrasound
The neuromuscular ultrasound is performed in B-mode (Brightness mode, two-dimensional image with gray levels) using the compound imaging of the corresponding sonographic device6,16. Compound imaging enables electronic control of the piezoelectric elements in the sonic probe (transducer) to illuminate the target structure from different angles17. The ultrasound waves are reflected in several directions due to the histological structure of the peripheral nerves. As a result of the sound coming from different angles, a more significant part of the otherwise lost reflections gets back to the sound probe (receiver) and can generate images. For neuromuscular ultrasound, a high-resolution ultrasound probe with 18 MHz linear array transducer, for deeper nerves, an additional 12 MHz linear array probe (e.g., to display tibial and fibular nerve in the popliteal fossa) is used6,16. Transducers with lower frequencies result in reduced spatial and lateral resolution so that the differentiation of the nerve boundaries from the surrounding structures is less precise. The optimal settings can be kept constant using a preset for neuromuscular imaging provided by the manufacturer. During the examination, the image depth and the focus position must be adjusted to the structure to be examined and constantly adapted to the position of the nerve. The B-image gain and the depth-dependent gain can be adjusted for image optimization with uniform brightness. Blood vessels are often close to neural structures and are often used as landmarks to make the measurements at the same position. To depict their anatomical interaction and distinguish between nerves and vessels, it is also necessary to display the flow velocity and direction using pulsed Doppler and color-coded duplex sonography16,18. The pulse repetition frequency must be adapted to the expected low flow velocities in the blood vessels of the extremities, or the power Doppler must be selected for color-coding16.
Nerves reflect the ultrasound waves differently from different angles of incidence so that the sonographic image varies in echogenicity (anisotropy)16,19. The best image is achieved from an orthograde angle since the ultrasonic waves are reflected most strongly by the nerves in this angle. For avoiding artificial anisotropy or nerve deformity, the probe must therefore be held in a neutral position during the examination without applying additional pressure perpendicular to the nerves (Figure 1). The cross-sectional area (CSA) is measured within the thin, hyperechoic epineurium (Figure 2) to avoid alterations of the epinerval tissue in the measurement19. More details on technical ultrasound can be found in References6,16,17,18,19,20,21.
All examinations for this work were performed in compliance with institutional guidelines of the Ruhr-University Bochum, Germany.
1. Experimental preparations
2. Ultrasound examination
Each ultrasound laboratory should establish its CSA reference values by collecting data from the healthy local population, as specific ultrasound machines and examiner or population-dependent variables can lead to slightly different results in each laboratory. However, to indicate which CSA values can be considered normal, data from two leading German nerve ultrasound groups and a recent meta-analysis of all published reference values so far13,14,
Nerve ultrasound is a helpful additional diagnostic tool in polyneuropathies. It can give information on the possible causes of polyneuropathy depending on the extent and pattern of nerve enlargement. Moreover, CSA alterations in the longitudinal disease course of patients with CIDP were described to correlate to clinical disease course and treatment response33,34,35,36.
The authors declare no conflicts of interest related to this manuscript.
We acknowledge the support from Ruhr-University Bochum for our research on neuromuscular ultrasound.
Name | Company | Catalog Number | Comments |
Affiniti 70 | Philips GmbH | n/a | with preset for neuromuscular ultrasound |
L18-5 linear array transducer | Philips GmbH | n/a | |
Ultrasound gel | C + V Pharma Depot GmbH | n/a |
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