Evaluation of peripheral nerve lesions with high-resolution ultrasonography and color Doppler
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.190269
Source of Support: None, Conflict of Interest: None
Keywords: High-resolution sonography; leprosy; peripheral nerve; peripheral nerve trauma; peripheral nerve tumor
The sonographic study of peripheral nerves began in 1988 when Bruno Fornage described the sonographic features of the peripheral nerves and associated masses. Today, technological advances in diagnostic sonography and ultrasound transducers allow the peripheral nerves to be traced in their entire length with structural delineation upto the fascicular level. This has broadened the spectrum of peripheral nerve diseases that can be examined sonographically, allowing the diagnosis and guided treatment of nerve disorders that were previously deemed inaccessible.
Thirty adult patients of either sex with suspected peripheral nerve lesions were included in the study. Thirty healthy adult volunteers were selected from the patient's relatives/hospital employees/colleagues. The study was conducted over a period of 18 months from November 2012 to April 2014. It was approved by the institutional ethics committee and review board, and informed consent was obtained from both the patients and the controls.
Clinical findings and details of relevant examination such as the nerve conduction study were noted. The sonographic procedure was explained to the patients and healthy normal volunteers, and written informed consent in vernacular language was obtained. All patients and controls were examined in the supine position, except for the evaluation of sciatic and posterior tibial nerves, where the patients were examined in the prone position.A detailed sonographic examination of the relevant peripheral nerve was then done using 5–17-MHz compact linear array transducer (iU22; Philips Medical Systems, Eindhoven, the Netherlands), and the peripheral nerve lesions were evaluated as follows:
The sonographic findings were then compared with the clinical findings and other laboratory reports.
Similar parameters were recorded for the 30 healthy adult volunteers. For each case of DPN, carpal tunnel syndrome, and leprosy patients, age and sex-matched controls were selected from this group for comparison of sonographic findings.
Results obtained on the basis of high-resolution sonographic study of peripheral nerves of the patients were compared with those of healthy normal volunteers using the SPSS Inc. Released 2008. SPSS Statistics for Windows, Version 17.0. (SPSS IBM Inc., Chicago). Student t-test was used to compare the means. A P value of less than 0.05 was considered to indicate a statistically significant difference.
Peripheral nerves were easily identified using high-resolution sonography by their predictable anatomic location and characteristic appearance [Figure 1].
Diabetic peripheral neuropathy
Five diabetic peripheral neuropathy patients, including 3 male and 2 female patients with a mean age of 56.6 years, were studied. For comparison, age and sex-matched controls were selected for each patient and examined with high-resolution sonography. On high-resolution sonography, there was a diffuse thickening of the peripheral nerve in these patients, and the mean CSA of median nerve and ulnar nerve was found to be significantly higher in patients with DPN when compared to normal matched controls [Figure 2]. On color Doppler assessment, no increase in vascularity was noted.
The mean CSA of the median nerve of patients with DPN was 10.5 mm 2 in the carpal tunnel and 8.69 mm 2 in the forearm 10 cm proximal to the wrist, whereas the CSA was 7.1 mm 2 and 5.89 mm 2, respectively at the same levels in controls. The P values for the CSA of the median nerve of patients with DPN and controls were <0.0001 at the level of carpal tunnel and 0.0004 at the forearm, implying that the difference in CSA was significant. Similarly, the difference in CSA of ulnar nerve between the DPN patients and age and sex-matched controls were also significant, the P values being 0.042 and 0.0052 for the CSA in Guyon's canal and behind the medial epicondyle, respectively [Table 1].
[Table 1] shows the comparison between the CSA of median nerve and ulnar nerve of the patients (with DPN, carpal tunnel syndrome, and leprosy) and age and sex-matched controls.
Carpal tunnel syndrome
Six cases of carpal tunnel syndrome diagnosed by nerve conduction study (NCS) were included in the study. For comparison, age, sex, and side-matched controls were taken for each patient. All the patients with carpal tunnel syndrome were females with a mean age of 45.75 years.
The mean CSA of the median nerve at the carpal tunnel of patients suffering from carpal tunnel syndrome was 13.9 mm 2 whereas that of matched controls was 7.89 mm 2, and this difference in CSA was statistically significant (P < 0.0001) [Figure 3] and [Table 1]. The mean CSA of median nerve at the forearm, of patients with carpal tunnel syndrome, was also more than that of age-matched controls; however, this was not statistically significant (P = 0.19). There was a significant difference in the wrist-forearm ratio (which is the ratio of the CSA of the median nerve at the carpal tunnel with that in the forearm) between the patients with carpal tunnel syndrome and matched controls. All the 6 patients with median nerve involvement manifesting as carpal tunnel syndrome showed a central intraneural vascularity, while none of the median nerves in controls showed intraneural vascularity [Figure 3]c.
Eight cases of leprosy (16 ulnar and 16 median nerve involvement), including 5 male and 3 female patients, with a mean age of 28.25 years were studied. For each case of leprosy, an age and sex-matched control was selected for comparison.
Only 2 of the 16 median nerves examined in the patients were clinically palpable in the carpal tunnel and in the forearm, while on sonography, there was a significant thickening (CSA > mean CSA of age and sex-matched controls + 2 standard deviation) of 8 median nerves in the carpal tunnel and 4 median nerves in the forearm [Table 1]. No ulnar nerve was palpable in the Guyon's canal in patients with leprosy, while on sonography, there was a significant thickening of 10 ulnar nerves in the Guyon's canal. On sonography, there was a significant thickening of the 9 ulnar nerves behind the medial epicondyle, which were all palpable clinically. This shows that clinical examination is unreliable for median nerve and ulnar nerve thickening in the Guyon's canal, whereas it is accurate in diagnosing significant ulnar nerve thickening behind the medial epicondyle.
There was significant thickening of the median and ulnar nerves in leprosy patients compared to age and sex-matched controls [Figure 4]. Patients with leprosy showed a focal and multifocal involvement, as opposed to diffuse involvement in DPN. In leprosy, there was an abnormal echopattern, hypoechogenecity and thickened fascicles [Figure 5]a and [Figure 5]b. Median and ulnar nerves in some patients with leprosy showed an increased vascularity [Figure 5]c and [Figure 5]d. Sonography was also sensitive in detecting complications of leprosy such as an intraneural abscess, which was detected in 2 patients, and neural and perineural inflammation, which was detected in 3 patients. Intraneural abscess was seen as a relatively well defined, heterogeneously hypoechoic area within the nerve with moving internal echoes and peripheral vascularity, whereas perineural inflammation was seen as an ill-defined heterogeneity adjacent to the nerve trunk with vascularity within [Figure 6].
The CSA of the median nerve in the carpal tunnel and the ulnar nerves in the Guyon's canal and behind the medial epicondyle were more in leprosy patients as compared to DPN patients. This increase in CSA was statistically significant behind the medial epicondyle (P = 0.047). The ulnar nerve behind the medial epicondyle showed an abnormal echopattern in 60% of DPN cases and 56.25% of leprosy cases. An abnormal echopattern was not observed in the median nerve and the ulnar nerve in Guyon's canal in DPN patients, while it was present in leprosy patients; 12.5% of the median nerves in the carpal tunnel, 18.75% of the median nerves in the forearm, and 25% of the ulnar nerves in the Guyon's canal showed an abnormal echopattern [Table 2].
There were 6 cases of neurogenic tumors, of which 5 were schwannomas and 1 was a neurofibroma. Four of the patients were male and 2 female, with a mean age of 42.25 years.
All the tumors had a hypoechoic appearance, and continuity with parent nerve could be appreciated [Figure 7]. On color Doppler, all the cases showed an internal vascularity [Figure 7]c and [Figure 8]b. One of the schwannomas was located eccentrically whereas the rest were located centrally in the peripheral nerves and showed a heterogeneous appearance with cystic areas within [Figure 8]. Both the schwannomas and the neurofibroma had a similar sonographic appearance, making it impossible to differentiate them by sonography; however, an eccentric location and marked heterogeneity favored the diagnosis of a schwannoma.
A total of 6 patients who had sustained trauma to the nerves were studied. They included 5 male patients and 1 female patient, all <30 years of age, with a mean age of 19 years. All the patients in the study had suffered from trauma of the upper limb nerves; 3 median nerves, 2 ulnar nerves, and 1 radial nerve. The epineurium could be easily visualized and nerve injury could be classified as exonotmesis, partial transection, and complete transection. All the 6 nerves involved in trauma showed thickening [Figure 9]. Other sonographic features seen were the development of a scar tissue, discontinuity in the epineurium, and a neuroma. Complete discontinuity of the epineurium was found in 1 case suggesting complete transection, and partial discontinuity suggesting partial transection was found in 2 cases [Figure 10]. The epineurium of rest of the 3 nerves were continuous. The neuroma appeared as a hypoechoic structure with no vascularity [Figure 11].
Peripheral nerves can be easily identified by their predictable anatomic location and characteristic appearance. On longitudinal scanning, the nerves were visualized as multiple hypoechoic bands, corresponding to the neuronal fascicle, and separated by hyperechoic lines, corresponding to the perineurium. A bright rim, the epineurium, bordered each nerve. Axial scanning revealed a honeycomb appearance with a network of hypoechoic rings separated by hyperechoic lines. In the regions where peripheral nerves were accompanied by vascular structures, the use of color Doppler could help in the distinction of nerves from vessels. This was helpful in differentiating the ulnar nerve from ulnar artery in the Guyon's canal.
High-resolution sonography showed a significant increase in the CSA of median and ulnar nerves in the DPN patients compared to age and sex-matched controls. No increase in the intraneural or perineural vascularity was noted. Similar findings have been reported by many of the recent studies.,, In DPN, there is diffuse involvement of the peripheral nerve, and in leprosy, there are no focal lesions. Peripheral nerve swelling in the setting of DPN presumably stems from an increased water content as a by-product of the aldose reductase conversion process of glucose into sorbitol.
Carpal tunnel syndrome is a common condition, affecting an estimated 500 in 100,000 persons per year or 1–2% of the total adult population. Six median nerves with carpal tunnel syndrome were studied, and there was a significant increase in the CSA of the median nerve in the carpal tunnel (P < 0.0001) and of the wrist forearm ratio (P = 0.0003) in these patients compared to age and sex-matched controls. Many explanations have been suggested for the increase in size of the nerve proximal to the site of entrapment such as endoneurial oedema, disturbance of axonal transport, and inflammation. Central intraneural vascularity was also observed in all the affected nerves, whereas none of the median nerves in age and sex-matched controls showed intraneural vascularity. Many previous studies have also reported similar findings.,,,,,
Leprosy is the most common treatable peripheral nerve disorder worldwide. Sonography showed a significant thickening of both the ulnar and median nerves in patients with leprosy when compared to age and sex-matched controls. This nerve thickening was more extensive and involved more nerves than was clinically diagnosed. The study also showed that clinical examination is unreliable in detecting significant thickening of the median and ulnar nerves, except for the finding of ulnar nerve thickening behind the medial epicondyle. Ulnar and median nerves in patients with leprosy also showed abnormal echopatterns, intraneural vascularity, intraneural abscesses, and intraneural and perineural inflammation. These findings were consistent with other sonography based studies conducted among leprosy patients.,
Both patients with DPN and leprosy showed diffuse thickening of the peripheral nerves. However, the nerve thickening was significantly more behind the medial epicondyle in the patients having leprosy compared to patients with DPN. Abnormal echopatterns, focal lesions with thickening, and increased vascularity were not seen in DPN patients while they were present in leprosy patients.
Among neurogenic tumors, both schwannomas and neurofibromas appear hypoechoic with vascularity within its substance. Most of the neurogenic tumors were located in the central part of the nerve except the single case of schwannoma, which was eccentric in location. These characteristic appearances of neurogenic tumors have also been described in few other studies., Sonography was not able to differentiate a schwannoma from a neurofibroma because of their similar imaging appearance; however, an eccentric location of the tumor favoured a schwannoma.
Traumatic peripheral nerve injuries occur from a variety of causes and their prevalence among patients who have had a traumatic injury is approximately 2.8%. Such injuries are increasingly recognized because of improved trauma services. In our study, remote traumatic injuries involving 6 peripheral nerves were studied. All the cases involved the upper limb nerves and majority of the patients were males. The nerve which was suspected to be injured could be identified in all cases, and sonographic features correlated with clinical symptomatology. Other studies have also reported a high sensitivity and specificity for the detection of peripheral nerve injury by sonography., The most common sonographic features observed in nerve trauma was nerve thickening, which was noted in all the cases. The epineurium was seen as an echogenic line surrounding the nerve, and could be identified in all the cases. It was normal in 3 cases, showed partial discontinuity in 2 cases, and showed complete discontinuity in 1 case, suggestive of complete transection of the nerve. Intraneural and perineural scar tissue were present in 4 cases but absent in 2 cases. Two of the injured nerves showed a neuroma, which results from random proliferation of axons, The Schwann cells and fibroblasts, were admixed together to form a non-neoplastic mass. Out of this, one was an end neuroma seen in a patient with complete transection of the radial nerve, and the other was a side neuroma seen in another patient with partial transection of the median nerve. The neuroma appeared as an irregular hypoechoic structure within the nerve at the site of trauma with no internal vascularity. The imaging appearance of a traumatic neuroma in our study was the same as described in previous studies.
Our study showed that a high-resolution sonography is an adequate and cost-effective noninvasive method for evaluating peripheral nerve disorders. Careful examination with an accurate scanning technique and a good knowledge of the anatomic relationships of the nerves to the surrounding structures provides an accurate information to the clinician for selecting the appropriate treatment. It may be used either as a first-line imaging modality in patients with suspected peripheral nerve lesions before further treatment is administered. It is also extremely useful for follow-up imaging. Ultrasonography permits the direct assessment of pathologic changes in nerve structures and/or in the adjacent tissue. These nerve lesions were traditionally diagnosed on the basis of clinical history, physical examination, and electrophysiological studies, including electromyography and nerve conduction studies. Although electrophysiological studies are helpful in determining the location and severity of the underlying nerve injury, they cannot determine the structural causes of denervation. Magnetic resonance imaging can be used to evaluate the peripheral nerve and localize the lesion; however, it has the limitations of availability and cost.
The main limitation in our study was that the number of patients with each of the pathological conditions were too few for a statistically significant result to be obtained. This was mainly due to the short duration of the study. Further, all the cases of nerve trauma studied were follow-up cases; larger studies are needed to evaluate the utility of high-resolution sonography in diagnosing acute nerve injury. An important limitation is that musculoskeletal ultrasound is an operator-dependent modality, which needs focused training.
I am greatly indebted to Dr. Vinod Puri, Director Professor and Head, Department of Neurology, GB Pant Hospital and Dr. MM Mehndiratta, former Director Professor, Department of Neurology, GB Pant Hospital for their support and suggestions in carrying out this study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11]
[Table 1], [Table 2]