The role of imaging in focal neuropathies.

Electrodiagnostic testing (EDX) has been the diagnostic tool of choice in peripheral nerve disease for many years, but in recent years, peripheral nerve imaging has been used ever more frequently in daily clinical practice. Nerve ultrasound and magnetic resonance (MR) neurography are able to visualize nerve structures reliably. These techniques can aid in localizing nerve pathology and can reveal significant anatomical abnormalities underlying nerve pathology that may have been otherwise undetected by EDX. As such, nerve ultrasound and MR neurography can significantly improve diagnostic accuracy and can have a significant effect on treatment strategy. In this chapter, the basic principles and recent developments of these techniques will be discussed, as well as their potential application in several types of peripheral nerve disease, such as carpal tunnel syndrome (CTS), ulnar neuropathy at the elbow (UNE), radial neuropathy, brachial and lumbosacral plexopathy, neuralgic amyotrophy (NA), fibular, tibial, sciatic, femoral neuropathy, meralgia paresthetica, peripheral nerve trauma, tumors, and inflammatory neuropathies.

Prognostic value of nerve ultrasonography: A prospective multicenter study on the natural history of chronic inflammatory neuropathies.

BACKGROUND AND OBJECTIVE: Nerve ultrasound is a promising new tool in chronic inflammatory neuropathies. The aim of this study was to determine its prognostic value in a prospective multicenter cohort study including incident and prevalent patients with CIDP and MMN. METHODS: We enrolled 126 patients with CIDP, and 72 with MMN; 71 were treatment-naive. Patients with chronic idiopathic axonal polyneuropathy (CIAP; n = 35) were considered as disease controls. Standardized neurological examination, questionnaires, and nerve ultrasonography were obtained at time of inclusion and 1-year follow-up. Nerve size development over time and correlation between nerve size and clinical outcome measures were determined using linear mixed effects models. RESULTS: Nerve size development over time was heterogeneous. Only in MMN was there a correlation between C5 nerve root size and deterioration of grip strength (-1.3 kPa/mm2 (95% confidence interval [CI] -2.3 to -0.2). No other significant correlations between nerve size and clinical outcome measures were found. In MMN, presence of nerve enlargement at inclusion predicted deterioration of grip strength, and MMN patients with enlargement confined to the brachial plexus seemed to have more favorable outcomes. No other predictive effects of sonographic nerve size were found. CONCLUSIONS: The present study indicates that the natural course of nerve size development in CIDP and MMN is heterogeneous, and that the prognostic value of sonographic nerve enlargement is limited. It had some predictive effect in patients with MMN. Further research in specific subgroups of chronic inflammatory neuropathy is necessary to determine the usefulness of nerve ultrasonography after the diagnostic phase.

Ultrasound scanning in the diagnosis of peripheral neuropathies.

Nerve ultrasound scanning has become a valuable diagnostic tool in the routine workup of peripheral nerve disorders, effectively complementing conventional electrodiagnostic studies. The most relevant sonographic features are nerve size and structural integrity. Several peripheral neuropathies show characteristic and distinct patterns of nerve enlargement, allowing their early and accurate identification, and reducing test-burden and diagnostic delay for patients. In mononeuropathies such as carpal tunnel syndrome and ulnar neuropathy at the elbow, nerve enlargement develops only at specific sites of entrapment, while in polyneuropathy the nerve enlargement may be multifocal, regional or even diffuse. Nerve ultrasound scanning can reliably identify chronic inflammatory neuropathies, even when extensive electrodiagnostic studies fail, and it should therefore be embedded in routine diagnostic workup of peripheral neuropathies. In this paper we describe a potential diagnostic strategy to achieve this.

Nerve ultrasound for diagnosing chronic inflammatory neuropathy: A multicenter validation study.

OBJECTIVE: To validate the diagnostic accuracy of a previously described short sonographic protocol to identify chronic inflammatory neuropathy (CIN), including chronic inflammatory demyelinating polyneuropathy (CIDP), Lewis Sumner syndrome, and multifocal motor neuropathy (MMN), and to determine the added value of nerve ultrasound to detect treatment-responsive patients compared to nerve conduction studies (NCS) in a prospective multicenter study. METHODS: We included 100 consecutive patients clinically suspected of CIN in 3 centers. The study protocol consisted of neurologic examination, laboratory tests, NCS, and nerve ultrasound. We validated a short sonographic protocol (median nerve at forearm, upper arm, and C5 nerve root) and determined its diagnostic accuracy using the European Federation of Neurological Societies/Peripheral Nerve Society criteria of CIDP/MMN (reference standard). In addition, to determine the added value of nerve ultrasound in detecting treatment-responsive patients, we used previously published diagnostic criteria based on clinical, NCS, and sonographic findings and treatment response (alternative reference standard). RESULTS: Sensitivity and specificity of the sonographic protocol for CIN according to the reference standard were 87.4% and 67.3%, respectively. Sensitivity and specificity of this protocol according to the alternative reference standard were 84.6% and 72.8%, respectively, and of NCS 76.1% and 93.4%. With addition of nerve ultrasound, 44 diagnoses of CIN were established compared to 33 diagnoses with NCS alone. CONCLUSIONS: A short sonographic protocol shows high diagnostic accuracy for detecting CIN. Nerve ultrasound is able to detect up to 25% more patients who respond to treatment. CLASSIFICATION OF EVIDENCE: This multicenter study provides Class IV evidence that nerve ultrasound improves diagnosis of CIN.

Nerve ultrasound improves detection of treatment-responsive chronic inflammatory neuropathies.

OBJECTIVE: To examine the diagnostic accuracy of nerve ultrasound in a prospective cohort of consecutive patients with a clinical suspicion of chronic inflammatory neuropathies, including chronic inflammatory demyelinating polyneuropathy, Lewis-Sumner syndrome, and multifocal motor neuropathy, and to determine the added value in the detection of treatment-responsive patients. METHODS: Between February 2015 and July 2018, we included 100 consecutive incident patients with a clinical suspicion of chronic inflammatory neuropathy. All patients underwent nerve ultrasound, extensive standardized nerve conduction studies (NCS), and other relevant diagnostic investigations. We evaluated treatment response using predefined criteria. A diagnosis of chronic inflammatory neuropathy was established when NCS were abnormal (fulfilling criteria of demyelination of the European Federation of Neurological Societies/Peripheral Nerve Society) or when the degree of nerve enlargement detected by sonography was compatible with chronic inflammatory neuropathy and there was response to treatment. RESULTS: A diagnosis of chronic inflammatory neuropathy was established in 38 patients. Sensitivity and specificity of nerve ultrasound and NCS were 97.4% and 69.4% and 78.9% and 93.5%, respectively. The added value of nerve ultrasound in detection of treatment-responsive chronic inflammatory neuropathy was 21.1% compared to NCS alone. CONCLUSIONS: Nerve ultrasound and NCS are complementary techniques with superior sensitivity in the former and specificity in the latter. Addition of nerve ultrasound significantly improves the detection of chronic inflammatory neuropathies. Therefore, it deserves a prominent place in the diagnostic workup of chronic inflammatory neuropathies. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that nerve ultrasound is an accurate diagnostic tool to detect chronic inflammatory neuropathies.

Nerve ultrasound: A reproducible diagnostic tool in peripheral neuropathy.

OBJECTIVE: To determine interobserver variability of nerve ultrasound in peripheral neuropathy in a prospective, systematic, multicenter study. METHODS: We enrolled 20 patients with an acquired chronic demyelinating or axonal polyneuropathy and 10 healthy controls in 3 different centers. All participants underwent an extensive nerve ultrasound protocol, including cross-sectional area measurements of median, ulnar, fibular, tibial, and sural nerves, and brachial plexus. Real-time image acquisition was performed blind by a local and a visiting investigator (reference). Five patients were investigated using different types of sonographic devices. Intraclass correlation coefficients were calculated, and a random-effects model was fitted to identify factors with significant effect on interobserver variability. RESULTS: Systematic differences between measurements made by different investigators were small (mean difference 0.11 mm2 [95% confidence interval 0.00-0.23 mm2]). Intraclass correlation coefficients were generally higher in arm nerves (0.48-0.96) than leg nerves (0.46-0.61). The hospital site and sonographic device did not contribute significantly to interobserver variability in the random-effects model. CONCLUSIONS: Interobserver variability of nerve ultrasound in peripheral neuropathy is generally limited, especially in arm nerves. Different devices and a multicenter setting have no effect on interobserver variability. Therefore, nerve ultrasound is a reproducible tool for diagnostics in routine clinical practice and (multicenter) research.

Nerve ultrasound shows subclinical peripheral nerve involvement in neurofibromatosis type 2.

INTRODUCTION: Neurofibromatosis type 2 (NF2) is mainly associated with central nervous system (CNS) tumors. Peripheral nerve involvement is described in symptomatic patients, but evidence of subclinical peripheral nerve involvement is scarce. METHODS: We conducted a cross-sectional pilot study in 2 asymptomatic and 3 minimally symptomatic patients with NF2 to detect subclinical peripheral nerve involvement. Patients underwent clinical examination, nerve conduction studies (NCS), and high-resolution ultrasonography (HRUS). RESULTS: A total of 30 schwannomas were found, divided over 20 nerve segments (33.9% of all investigated nerve segments). All patients had at least 1 schwannoma. Schwannomas were identified with HRUS in 37% of clinically unaffected nerve segments and 50% of nerve segments with normal NCS findings. DISCUSSION: HRUS shows frequent subclinical peripheral nerve involvement in NF2. Clinicians should consider peripheral nerve involvement as a cause of weakness and sensory loss in the extremities in patients with this disease. Muscle Nerve 57: 312-316, 2018.

High-resolution ultrasound in patients with Wartenberg's migrant sensory neuritis, a case-control study.

OBJECTIVE: Wartenberg's migrant sensory neuritis (WMSN) is a rare, patchy, pure sensory neuropathy of unknown etiology. High-resolution ultrasonography (HRUS) is an emerging diagnostic technique for neuropathies, but it has not been applied in WMSN. In this study we aimed to determine HRUS abnormalities in WMSN. METHODS: We performed a case-control study of 8 newly diagnosed patients with WMSN and 22 treatment-naive disease controls (16 patients with pure sensory axonal neuropathy and 6 with pure sensory chronic inflammatory demyelinating polyneuropathy (CIDP) or Lewis-Sumner syndrome (LSS)). All patients underwent routine diagnostic evaluations and a predefined HRUS protocol. RESULTS: We found multifocal nerve enlargement in all 8 WMSN patients. The median nerve in the upper arm and the sural nerve were significantly larger in WMSN than in axonal controls (p = 0.01 and p = 0.04). In CIDP/LSS, sonographic enlargement was more extensive. Furthermore we found brachial plexus involvement in 3 of 8 (38%) WMSN patients. CONCLUSION: HRUS showed enlargement of multiple nerves in all WMSN patients even if clinical testing and NCS were normal. SIGNIFICANCE: The feature of multifocal nerve enlargement may be of additional value in establishing the diagnosis of WMSN and may support the suggestion of an auto-immune etiology.

Nerve ultrasound in polyneuropathies.

Ultrasound can be used to visualize pathology in the peripheral nerves of patients with polyneuropathy. Nerve enlargement is the most frequent pathology, but other abnormalities, including abnormal nerve echogenicity and vascularity, are also encountered. This monograph presents an overview of the role of nerve ultrasound in the evaluation and management of both inherited and acquired polyneuropathies. A description of the sonographic techniques and common abnormalities is provided, followed by a presentation of typical findings in different neuropathies. Scoring systems for characterizing the presence and pattern of nerve abnormalities as they relate to different polyneuropathies are presented. Muscle Nerve 57: 716-728, 2018.

Nerve ultrasound in neurofibromatosis type 1: A follow-up study.

OBJECTIVE: To investigate development of sonographic abnormalities and applications of high-resolution ultrasonography (HRUS) in neurofibromatosis type 1 (NF1). METHODS: Sixteen asymptomatic or minimally symptomatic NF1 patients underwent HRUS at inclusion and 1 year follow-up. Upper and lower extremity nerves were investigated. Peripheral nerve involvement was graded. RESULTS: Plexiform neurofibromas (PNFs) were found in 7 patients (43.8%) at inclusion and 10 (62.5%) at follow-up. All initially identified PNFs were also found at follow-up; additional PNFs were found by extended longitudinal assessment at follow-up. All 3 patients with minor and 7 patients with severe peripheral nerve involvement had similar involvement at follow-up. Mean nerve size change was -0.2 mm2 (±1.6) and 0.3 mm2 (±6.2) in patients with minor and severe involvement. Mean PNF size change was -0.1 mm2 (±9.9). CONCLUSIONS: HRUS allows qualitative assessment of peripheral nerves, which makes it advantageous as initial imaging technique in suspected neuropathy. Patients with minimal nerve involvement remained so, and might therefore require less follow-up for malignant peripheral nerve sheath tumor (MPNSTs) development. Measured change in PNF size was highly variable. Repeating an extensive standardized HRUS protocol during follow-up thus seems less useful to screen for MPNSTs. SIGNIFICANCE: HRUS has potential applications as diagnostic and screening tool in NF1.

Extensive sonographic ulnar nerve enlargement above the medial epicondyle is a characteristic sign in Hansen's neuropathy.

OBJECTIVE: Earlier studies have shown sonographic enlargement of the ulnar nerve in patients with Hansen's neuropathy. The present study was performed to determine whether sonography or electrophysiological studies can detect the specific site of ulnar nerve pathology in leprosy. METHODS: Eighteen patients (thirty arms) with Hansen's disease and an ulnar neuropathy of whom 66% had borderline tuberculoid (BT), 27% lepromatous leprosy (LL) and 7% mid-borderline (BB) leprosy were included in the study. Cross-sectional area (CSA) of ulnar nerve was measured every two centimeters from wrist to medial epicondyle and from there to axilla. All patients underwent standard motor and sensory nerve conduction studies of the ulnar nerve. Thirty age and sex matched controls underwent similar ulnar nerve CSA measurements and conduction studies. RESULTS: Ulnar nerve was clinically palpable in 19 of the 30 arms of patients. Motor and sensory nerve conduction studies of the ulnar nerve showed a reduced compound motor action potential and sensory nerve action potential amplitude in all patients. Motor Conduction Velocity (MCV) in patients were slower in comparison to controls, especially at the elbow and upper arm, but unable to exactly locate the site of the lesion. In comparison to controls the ulnar nerveCSA was larger in the whole arm in patients and quite specific the maximum enlargement was seen between nulnar sulcus and axilla, peaking at four centimeters above the sulcus. CONCLUSIONS: A unique sonographic pattern of nerve enlargement is noted in patients with ulnar neuropathy due to Hansen's disease, while this was not the case for the technique used until now, the electrodiagnostic testing. The enlargement starts at ulnar sulcus and is maximum four centimeters above the medial epicondyle and starts reducing further along the tract. This characteristic finding can help especially in diagnosing pure neuritic type of Hansen's disease, in which skin lesions are absent, and alsoto differentiate leprosy from other neuropathies in which nerve enlargement can occur.

Nerve ultrasound: A useful screening tool for peripheral nerve sheath tumors in NF1?

OBJECTIVE: To determine ultrasonographic peripheral nerve involvement in patients with asymptomatic neurofibromatosis type 1 (NF1). METHODS: Thirteen asymptomatic and 4 minimally symptomatic patients with NF1 were included in this cross-sectional pilot study to detect asymptomatic abnormalities of the brachial plexus and upper and lower extremity nerves. Patients underwent clinical examination, nerve conduction studies (NCS), and high-resolution ultrasonography (HRUS). RESULTS: HRUS showed abnormalities in 16 patients (94.1%). Neurofibromas were identified in 10 patients (58.8%): localized neurofibromas were found in 3 patients (17.6%), plexiform neurofibromas in 3 (17.6%), and both in 4 (23.5%). In 6 patients (35.3%), only nerve enlargement without an abnormal fascicular pattern was observed. Severe involvement of the peripheral nervous system with multiple plexiform neurofibromas was observed in 7 patients (41.2%), while 4 patients (23.5%) had no or only minor involvement. Both NCS and HRUS were performed on 73 individual nerve segments. In 5.5%, abnormalities were found with both tests; in 50.7%, only with HRUS; and in 1.4%, only with NCS. CONCLUSIONS: HRUS frequently showed subclinical involvement of the peripheral nerves in NF1, also when NCS were normal. HRUS findings ranged from normal to widespread peripheral nerve involvement. Because the presence of plexiform neurofibromas and the benign tumor load are risk factors for the development of a malignant peripheral nerve sheath tumor, HRUS may be a useful tool to identify a subgroup of patients who could benefit from regular follow-up.