We acknowledge the support from Ruhr-University Bochum for our research on neuromuscular ultrasound.

All examinations for this work were performed in compliance with institutional guidelines of the Ruhr-University Bochum, Germany.
1. Experimental preparations
<ol>
	<li>Patient preparation
	<ol>
		<li>Check the patient inclusion criteria: examine adult patients diagnosed with polyneuropathy, suspicious of inflammatory origin.</li>
		<li>Check the patient exclusion criteria: do not examine patients with open wounds or infections in the regions to be examined.</li>
	</ol>
	</li>
	<li>Instrumen...

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.
<p class="jove_cont...

Next to clinical examination, evaluating any large-fiber polyneuropathy includes an electrophysiological examination to characterize the motor or sensory system&#39;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&#160;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&#160;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.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Affiniti 70</td>
			<td>Philips GmbH</td>
			<td>n/a</td>
			<td>with preset for neuromuscular ultrasound</td>
		</tr>
		<tr>
			<td>L18-5 linear array transducer</td>
			<td>Philips GmbH</td>
			<td>n/a</td>
			<td></td>
		</tr>
		<tr>
			<td>Ultrasound gel</td>
			<td>C + V Pharma Depot GmbH</td>
			<td>n/a</td>
			<td></td>
		</tr>
	</tbody>
</table>

nerve ultrasound protocol to detect dysimmune 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.

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,<sup ...

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Nerve Ultrasound Protocol to Detect Dysimmune Neuropathies

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 ...

High resolution of ultrasound is used as an additional diagnostic tool to detect morphological alterations of the peripheral nerves such as increased cross-sectional area. In this immune neuropathy is like chronic inflammatory demyelinating polyneuropathy. The main advantage of nerve ultrasound is that it can be performed quickly, easily and without relevant risks directly by the neurologist.Nerve ultrasound can help to diagnose inflammatory neuropathies, but may also help in prognosis and follow-up of disease course. For examination of the arm nerves, let the patient sit in a neutral position with the arm resting supinated on a surface such as a leg. Then apply ultrasound gel over the transducer probe wrist, forearm, elbow and upper arm.To examine the median nerve perform a transverse scan at the wrist level. The median nerve can be easily identified in the carpal tunnel below the transverse carpal ligament next to the tendons of flexor digitorum superficialis and profundus. Then measure the cross-sectional area or CSA of the median nerve at the entrance to the carpal tunnel.Move the transducer proximally to follow the anatomical course of the median nerve to the forearm and measure the CSA at the forearm. Then follow the anatomical course to the elbow. Move the transducer proximally following the median nerve from the forearm to the elbow and measure the CSA at the elbow.Then follow the course to the upper arm. Move the transducer proximally following the median nerve from the elbow to the upper arm, and measure the CSA at the upper arm next to the brachial artery. Next, to examine the ulnar nerve, perform a transverse scan at the wrist level.The ulnar nerve can be identified at the wrist ulnar of the carpal tunnel directly next to the ulnar artery and pisiform bone where it enters Guyon's canal. Measure the CSA of the ulnar nerve at the entrance to Guyon's canal. Move the transducer proximally following the ulnar nerve from the forearm to the sulcus ulnaris at the elbow and then to the upper arm.After moving the transducer proximally from the wrist to the forearm, measure the CSA at the forearm. Follow the course of the ulnar nerve to the sulcus and measure the CSA at the sulcus ulnaris at the level of the elbow. Follow the anatomical course to the upper arm and measure the CSA.Next, to examine the radial nerve in the spiral groove, let the patient hold the arm in front of the stomach bent at the elbow. Then scan the radial nerve directly next to the humerus, using the color doppler mode to avoid confusion with the accompanying artery and vein. Color doppler mode shows blood flow in arteria profunda brachii and low flow in the corresponding vein while no flow occurs in the radial nerve.Additionally, the vein and artery can be compressed by exerting external pressure. Measure the CSA of the radial nerve in the spiral groove. Next to examine the vagal nerve, cervical nerve roots and brachial plexus, apply the ultrasound gel in the middle of the patient's neck.For the vagal nerve, perform a transverse scan at the middle of the neck and find the carotid artery and jugular vein. The vagal nerve can be found directly next to the carotid artery and jugular vein. Then measure the CSA of the vagal nerve at the carotid sheath at the level of the carotid bifurcation.Next, to examine the cervical nerve roots, C5, C6, and C7, move the probe dorsal and slide it slightly up and down. The cervical nerve roots appear between the anterior and posterior tubercle of the transverse process. C7 can be recognized by the absence of the anterior tubercle from its transverse process while both anterior and posterior tubercle are found with C5 and C6.Measure the CSA of the nerve roots in the intrascalene space proximal to the formation of the trunk eye in a cross-sectional view.Next, move the transducer distally following the trunks and plexus to the supraclavicular space. To examine the brachial plexus, follow the anatomical course of the cervical nerve roots distally and then find the trunks and cords of the plexus. Measure the CSA of the plexus at the supraclavicular space.Alternatively, for evaluation of the nerve roots perform a longitudinal scan to display nerve roots. Measure the diameter of the cervical nerve roots at the most proximal location where the nerve root exits over the transverse process in a longitudinal view. To continue examining the leg nerves let the patient lie down on one side with the leg slightly bent.Then place some ultrasound gel over the transducer probe, the popliteal fossa, the fibula and the lower leg. To examine the fibular nerve, feel the fibular head and place the transducer directly behind it. Identify the fibular nerve next to the fibular head.Measure the CSA of the fibular nerve next to the fibular head. Next, move the transducer proximally following the fibular nerve from the fibular head to the fossa poplitea. Then measure the CSA of the fibular nerve in the popliteal fossa.To examine the tibial nerve in the popliteal fossa find the fibular nerve again and the popliteal artery in the popliteal fossa. In most cases, the tibial nerve can be found just above the popliteal artery. Measure the CSA of the tibial nerve at the popliteal fossa.To avoid many changes in the patient's position, continue to examine the sural nerve in the same position before continuing with the tibial nerve on the medial malleolus. To examine the sural nerve place the probe at the lateral ankle. In most cases, the sural nerve can be found next to a superficial vein.Measure the CSA of the sural nerve between the lateral and medial head of the gastric anemia muscle. Finally, to examine the tibial nerve at the ankle let the patient sit or lie on their back with the knees slightly bent. Then place the ultrasound gel at the ankle and the probe directly behind the medial malleolus.The tibial nerve can be found just next to the posterior tibial artery. Measure the CSA of the tibial nerve at the level of the medial ankle. After performing all measurements on both sides save the results and end the examination.Reference CSA values for patients studied under this protocol are shown here. Representative images of the six nerve sites used in the adjusted Bochum ultrasound score in a healthy person are shown here. These sites are the median nerve at the forearm and upper arm, the radial nerve at the upper arm, the ulnar nerve at the forearm and at the upper arm and the sural nerve at the calf.Similar images of a patient with chronic inflammatory demyelinating polyneuropathy are shown here. Each of these six sites is scored with one point if the nerve shows pathological CSA enlargement on one or both sides of the body Immune neurography is another method to detect morphological alterations of the peripheral nerves especially for proximal leg nerves and lumbosacral plexus where nerve ultrasound is difficult to apply. Further research on neuromuscular ultrasound is interesting as the morphological alterations may give insights into pathophysiological aspects like inflammation.

Nerve Ultrasound Protocol to Detect Dysimmune Neuropathies

Abstract