Abstract
Background
The imaging diagnosis of intraneural vascular anomalies of peripheral nerves mostly depended on magnetic resonance imaging (MRI), whereas high-frequency ultrasonography evaluation of intraneural vascular anomalies has been seldom done.
Purpose
To evaluate the diagnostic value of ultrasonography in the diagnosis of intraneural vascular anomalies of peripheral nerves.
Material and Methods
A total of 69 consecutive patients seen at Shandong Provincial Hospital Affiliated to Shandong First Medical University between February 2013 and June 2022, each with a clinical suspicion of intraneural vascular anomaly, were included. The ultrasonographic images of intraneural vascular anomalies of peripheral nerves were analyzed and the ultrasonographic features were summarized. These data were compared with MRI, which served as the gold standard for the diagnosis of intraneural vascular anomalies. The kappa statistic was adopted to determine the level of agreement. The sensitivity, specificity, positive and negative predictive values, accuracy, and Youden index of high-frequency ultrasonography as a diagnostic tool were assessed.
Results
Ultrasonography findings were positive in 20 of 69 patients with a clinical suspicion of intraneural vascular anomaly. The diagnosis was confirmed by MRI in 21 patients. There was one false-positive result and two false-negative results by ultrasonography. The κ value was 0.896. The sensitivity, specificity, positive and negative predictive values, accuracy, and Youden index of ultrasonography were 90.5%, 97.9%, 95%, 95.9%, 95.7%, and 0.884, respectively.
Conclusion
Ultrasonography could be an accurate, reliable, and convenient imaging tool for the diagnosis of intraneural vascular anomalies of peripheral nerves.
Introduction
Intraneural vascular anomaly of the peripheral nerve is a relatively rare congenital benign malformation that often occurs in the upper limb nerve, most commonly in the median nerve, ulnar nerve, and their branches, occasionally involving the sciatic nerve and tibial nerve (1). It is often misdiagnosed as intraneural ganglion cyst or neurofibroma by clinicians. The literature on the diagnosis of intraneural vascular anomalies of peripheral nerves is mostly based on magnetic resonance imaging (MRI) (2–4). Ultrasound diagnosis is rarely reported in the literature. Ultrasonography is a convenient diagnostic method, and its usefulness of neuropathy examination is generally accepted (5). In this study, we analyzed the characteristics of ultrasonography in patients with intraneural vascular anomaly. The aim of the present study was to evaluate the value of ultrasonography in diagnosing intraneural vascular anomalies of the peripheral nerves.
Material and Methods
Between February 2013 and June 2022, 69 consecutive patients (36 male patients, 33 female patients; age range = 7–51 years; mean age = 24.87 ± 12.21 years) seen at Shandong Provincial Hospital Affiliated to Shandong First Medical University, each with a clinical suspicion of intraneural vascular anomaly of the peripheral nerve, were included. The study was approved by the institutional review board of Shandong Provincial Hospital Affiliated to Shandong First Medical University. All lesions were unilateral, including both upper limb nerves and lower limb nerves. Among the 69 patients, 55 patients showed local pain of limbs and more obvious when pressing, in which 21 of the 55 patients were complicated with pain and sensory abnormality in the nerve innervation area. The other 14 patients complained of local mass of limbs without obvious pain and numbness.
All patients in the study underwent ultrasonography using ultrasound systems with high-frequency array transducers (9–24 MHz) (Epiq 7, Washington, USA, Epiq 5, Washington, USA, Philips; Vivid 7 dimension, GE, Holten, Norway; and i800, Canon, Otawara-shi, Tochigi, Japan), while a 3–12 MHz transducer was adopted if the lesions were deep. Musculoskeletal preset condition was used in all examinations. First, continuous scanning in both the axial and longitudinal planes was performed on the nerves in which the lesion was located, such as the median nerve, ulnar nerve, radial nerve, sciatic nerve, tibial nerve, common peroneal nerve, and their branches. The focus was on the size, location, echogenicity, and involvement of intraneural vascular anomalies. Panoramic imaging was performed if necessary. Surface localization was performed for patients requiring surgery. Second, color Doppler ultrasound was used for the examination of blood flow. Attention was paid to the blood supply of intraneural vascular anomalies in order to determine the classification. Some patients needed to be properly pressurized to observe the blood flow filling inside the lesion. The prone position was adopted to detect lesions within the sciatic nerve if necessary. For the purpose of control, the contralateral upper or lower limbs were scanned.
All patients underwent MRI, which served as the gold standard for the diagnosis of intraneural vascular anomalies and the MRI findings were compared with ultrasound images. Non-contrast MRI images of T1-weighted (T1W) imaging, T2-weighted (T2W) imaging, fat-suppressed (FS) T1W imaging, and FS-T2W imaging sequences in the coronal, sagittal, and axial planes were obtained in order to observe the location, signal, and involvement of intraneural vascular anomalies using a 3.0-T MRI system (GE Healthcare) with a dedicated surface coil on the nerves in which the lesion was located and on the contralateral healthy nerve as a control.
All ultrasonography examinations were performed by a senior ultrasonography technician with more than 10 years of experience in peripheral nerve ultrasonography examination. All MRI examinations were performed by an experienced peripheral nerve radiologist with nine years of experience.
Ultrasound and MRI images of patients in the picture archiving and communication systems were then assessed by two radiologists independently, with >11 years of diagnostic experience in interpreting results of ultrasonography and MRI. The original reports were shielded to avoid bias.
The SPSS program (version 25.0; IBM Corp., Armonk, NY, USA) was used for statistical analysis. The level of agreement between ultrasonography and MRI was determined using the kappa test. Sensitivity, specificity, positive and negative predictive values, accuracy, and Youden index were obtained.
Results
Among the 69 patients with a clinical suspicion of intraneural vascular anomalies of peripheral nerves, there were 21 positive results and 48 negative results confirmed by MRI. The ultrasonography diagnosis was positive in 20 patients and negative in 49 patients. Compared to MRI, there was one false-positive result and two false-negative results by ultrasonography. Detailed clinical data and ultrasonography classification are summarized in Table 1. MRI and ultrasonography comparison results are shown in Table 2.
Detailed clinical profiles and US classification of intraneural vascular anomalies of peripheral nerves.
The patients were tested for intraneural ganglion cyst using magnetic resonance imaging.
AVM, arteriovenous malformation; US, ultrasound; VM, venous malformation.
Comparison of results: ultrasonography and MRI.
CT, computed tomography; MRI, magnetic resonance imaging.
In 20 patients with a positive ultrasonography diagnosis, ultrasonography revealed 16 cases of intramuscular venous malformation (VM) with nerve invasion and four cases of intraneural arteriovenous malformation (AVM). The affected nerves in 20 patients with intraneural vascular anomalies of peripheral nerves included eight median nerves, four ulnar nerves, two radial nerves, four tibial nerves, one common peroneal nerve, and one sciatic nerve (patient 13 in Table 1 with a positive diagnosis by ultrasonography was proved to be intraneural ganglion cyst by MRI). All other patients with a negative ultrasonography diagnosis presented negative findings on MRI except two patients with both muscle and nerve involvement, for whom ultrasonography only suggested VM in the muscle without making a diagnosis of the nerve. And intraneural vascular anomaly was confirmed by MRI in these patients.
The ultrasonographic features of intraneural vascular anomalies of peripheral nerves were the visualization of thickening nerves, within which tubular structures along the long axis of nerves could be observed, and the boundary between the vascular malformations and the fascicle was not clear. In patients with intraneural venous malformation, phlebolith or thrombus within the vascular malformations could be seen in 12 cases. Abundant low velocity venous blood flow could be detected on color Doppler examination. The morphological changes of nerves were obvious after pressure with the probe. In some cases, VMs could also be seen in the soft tissue around nerves. (Figs. 1 and 2). While in patients with intraneural AVMs, abundant arteriovenous blood flow with high peak systolic velocity (PSV) and low resistance index (RI) could be detected on the color and spectral Doppler examinations (Fig. 3). In four patients with intraneural vascular anomalies of peripheral nerves who received surgical treatment, the location, size, boundary, and involvement of the lesions were accurately assessed during the ultrasound examination, and ultrasound-guided body surface localization was consistent with the intraoperative findings (Fig. 4).
A 10-year-old male patient with a venous malformation involving the sciatic nerve. The ultrasound image shows (a) the normal sciatic nerve and (b) the affected sciatic nerve in axial view. (c) Hyperechoic phlebolith within the venous malformation could be seen (white arrow). (d) The longitudinal ultrasound image reveals the low velocity venous blood flow signal within the venous malformation of the affected sciatic nerve. SCIATIC N, sciatic nerve.
A 24-year-old female patient with a venous malformation involving the left forearm flexor muscle and MN. (a) The longitudinal ultrasound image of the affected MN (white arrow). (b) The axial ultrasound image reveals the venous malformation within the MN (short arrow) and the venous malformation in flexor muscle around the MN (long arrow). (c) Low velocity venous blood flow within the vascular anomalies of the affected MN could be detected by color Doppler examination. MN, median nerve.
A 21-year-old female patient with a arteriovenous malformation involving the RN. (a) The axial ultrasound image of the affected RN (white arrow). (b) The longitudinal color Doppler image reveals the abundant blood flow signal within the vascular anomalies of the affected RN (white arrow). (c) Arteriovenous blood flow with high PSV and low RI could be detected by spectral Doppler. Hu, humerus; PSV, peak systolic velocity; RI, resistance index; RN, radial nerve.
A 34-year-old male patient with a venous malformation involving the TN. (a) Ultrasonography, (b) fat-saturated T2-weighted sagittal image, and (c) intraoperative findings of intraneural venous malformation. TN, tibial nerve (white arrow).
The MRI features of the intraneural vascular anomalies of the peripheral nerves were similar to those of ultrasonography. MRI showed that the affected nerves were obviously enlarged. Most lesions had low signal intensity on T1W imaging and high signal intensity on T2W imaging. In addition, the boundary between the vascular anomalies and the fascicle was not clear (Fig. 4).
Analysis of internal validity parameters of ultrasonography as a diagnostic tool for intraneural vascular anomalies of the peripheral nerves showed a sensitivity of 90.5%, specificity of 97.9%, a positive predictive value of 95%, and a negative predictive value of 95.9%. The overall accuracy was 95.7%. The Youden index of ultrasonography was 0.884. The κ level of agreement between MRI and ultrasonography for diagnosing intraneural vascular anomalies of peripheral nerves was 0.896 (high level) (Table 3).
κ statistics between MRI and ultrasonography.
Approximate significance.
ASE, asymptotic standard error; MRI, magnetic resonance imaging.
For treatment, only four out of the 16 cases with intraneural VMs were resected. In the remaining 12 cases with intraneural VMs, only the sclerosing agent was injected into the intramuscular VMs around the nerve, leaving the intraneural VMs untreated. In the other four cases with intraneural AMVs, the feeding arteries of the AVM within the nerves were embolized under angiography.
Discussion
The International Society for the study of Vascular Anomalies classification for vascular anomalies (approved at the 20th ISSVA Workshop, Melbourne, April 2014, last revision May 2018) (6) divided angiogenic lesions into vascular tumors and vascular malformations according to their cytological characteristics and clinical behavior biology. The intraneural vascular anomalies of the peripheral nerves mainly include VMs and AVMs, which are rare benign peripheral neuropathies (7). They occur at birth and may not be obvious. They become obvious gradually with age and will not fade away by themselves. Most of them grow in equal proportion to the growth and development of patients. In 20 patients included in this study with intraneural vascular anomalies of the peripheral nerves, 16 cases of VM and four cases of AVM involving the peripheral nerves all had the vascular malformations around the affected peripheral nerves, which suggested that the presence of peripheral intraneural vascular anomaly alone is very rare, and mostly due to the invasion of the vascular malformation around the nerve. Therefore, when encountering vascular malformations around the nerve, attention should be paid to exclude the invasion of the nerves within the lesion area.
VMs, formerly known as cavernous hemangiomas (8), are essentially malformed venous networks. They consist of a large number of dilated venous vessels under a microscope. Only thin collagen fibers and endothelial cells are found in the vessel wall. Thrombosis and phlebolith are common. The ultrasonographic features of peripheral intraneural VMs are the visualization of thickening nerves, within which tubular structures along the long axis of nerves could be observed, and hypoechoic thrombosis and hyperechoic phlebolith within the vascular anomalies could be seen in some cases. AVMs are a large number of microscopically visible vascular fistulas formed by abnormal arteries and veins (9). AVMs have palpable tremor and high skin temperature on the surface of the body. Ultrasonography shows tortuous and dilated arteriovenous vessels within the thickening nerves. In addition, abundant arteriovenous blood flow spectrum with high PSV and low RI indicates the presence of arteriovenous fistulas.
Intraneural vascular anomalies of the peripheral nerves are mainly differentiated from intraneural ganglion cysts and neurofibromas among others (10). Intraneural ganglion cysts show cystic masses within the peripheral nerve; clear boundaries, irregular shape, ill-acoustic transmissibility, and separations are common. Color Doppler examination shows no blood flow inside the cysts. There are also no morphological changes of nerves after pressing with the probe. Although neurofibromas are intraneural masses along the long axis of nerves with a centric growth pattern, their echogenicity is higher than that of vascular malformations, and they are incompressible. In some cases, hyperechoic calcifications can be seen, and arterial blood flow signals can be detected by color and spectral Doppler examination.
Although MRI can also show vascular malformations in the peripheral nerves, it is expensive and takes a long time to scan. Compared to MRI, ultrasound is a more affordable, quicker, real-time dynamic and less stressing imaging choice on arbitrary sections (11). It can not only show the structure of the peripheral nerves, but also reveal the vascular malformations within or around the peripheral nerves, accurately locate the lesions and their scope of involvement, and determine their classification. More importantly, ultrasonography-guided local sclerotherapy is available (12). Last, but not least, it is a convenient and reliable imaging tool in the follow-ups of patients with intraneural vascular anomalies of the peripheral nerves after treatment.
The present study has some limitations. First, ultrasound examination itself has its limitations: operator dependence is one of the unavoidable problems, which requires familiarity with the anatomy of peripheral nerve examination in order to improve the diagnostic coincidence rate. Therefore, continuous scanning in both the axial and longitudinal planes should be performed on the nerves in which the lesion is located, and comparison scanning should be adopted on the contralateral upper or lower limbs as a control. Panoramic imaging should be performed if necessary. Second, the sample size is small. In order to get more concrete conclusion, the sample size should be expanded.
Regarding the treatment of vascular malformations, clinicians recommend either surgical or conservative treatment according to their type and extent. For VMs without invasion of peripheral nerves, sclerotherapy, such as anhydrous ethanol or foam sclerosing agent, should be adopted to destroy vascular endothelial cells, resulting in the occlusion of blood vessels. For AVM without invasion of the peripheral nerves, feeding artery embolization under angiography would be more appropriate. There are still many controversies over the treatment of intraneural vascular anomalies (13). At present, surgery is considered to be the most effective method of treatment (14), which is safer compared with peripheral neurosclerotherapy. The main surgical procedure is resection of vascular malformations within the peripheral nerves. However, it is difficult to completely resect the lesion without damaging the fascicle. In addition, neurotomy and nerve transplantation can be considered in complex or recurrent cases (15). In this study, only four cases of intraneural VM with limited lesions were resected. The other intraneural vascular anomalies of peripheral nerves with wider lesions were treated conservatively.
In conclusion, ultrasonography could be a reliable, accurate, and convenient diagnostic imaging tool in the assessment of patients with intraneural vascular anomalies of the peripheral nerves. It could provide essential imaging evidence for clinical diagnosis, treatment, and follow-ups. Further research should be carried out to increase its clinical application in the diagnosis and treatment of intraneural vascular anomalies of peripheral nerves.
Footnotes
Author note
Both Hengtao Qi and Tiezheng Wang contributed equally to this work and should be considered co-corresponding authors.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Shandong Provincial Natural Science Foundation (grant number ZR2022MH043).
