Imaging Biomarkers of Peripheral Nerves: Focus on Magnetic Resonance Neurography and Ultrasonography.

Peripheral neuropathy is a prevalent and debilitating condition affecting millions of individuals globally. Magnetic resonance neurography (MRN) and ultrasonography (US) are noninvasive methods offering comprehensive visualization of peripheral nerves, using anatomical and functional imaging biomarkers to ensure accurate evaluation. For optimized MRN, superior and high-resolution two-dimensional and three-dimensional imaging protocols are essential. The anatomical MRN and US imaging markers include quantitative measures of nerve and fascicular size and signal, and qualitative markers of course and morphology. Among them, quantitative markers of T2-signal intensity ratio are sensitive to nerve edema-like signal changes, and the T1-mapping technique reveals nerve and muscle tissue fatty and fibrous compositional alterations.The functional markers are derived from physiologic properties of nerves, such as diffusion characteristics or blood flow. They include apparent diffusion coefficient from diffusion-weighted imaging and fractional anisotropy and tractography from diffusion tensor imaging to delve into peripheral nerve microstructure and integrity. Peripheral nerve perfusion using dynamic contrast-enhanced magnetic resonance imaging estimates perfusion parameters, offering insights into nerve health and neuropathies involving edema, inflammation, demyelination, and microvascular alterations in conditions like type 2 diabetes, linking nerve conduction pathophysiology to vascular permeability alterations.Imaging biomarkers thus play a pivotal role in the diagnosis, prognosis, and monitoring of nerve pathologies, thereby ensuring comprehensive assessment and elevating patient care. These biomarkers provide valuable insights into nerve structure, function, and pathophysiology, contributing to the accurate diagnosis and management planning for peripheral neuropathy.

MRI Features of Pelvic Nerve Involvement in Endometriosis.

Endometriosis is a common condition that mostly affects people assigned as female at birth. The most common clinical symptom of endometriosis is pain. Although the mechanism for this pain is poorly understood, in some cases, the nerves are directly involved in endometriosis. Endometriosis is a multifocal disease, and the pelvis is the most common location involved. Nerves in the pelvis can become entrapped and involved in endometriosis. Pelvic nerves are visible at pelvic MRI, especially when imaging planes and sequences are tailored for neural evaluation. In particular, high-spatial-resolution anatomic imaging including three-dimensional isotropic imaging and contrast-enhanced three-dimensional short inversion time inversion-recovery (STIR) fast spin-echo sequences are useful for nerve imaging. The most commonly involved nerves are the sciatic, obturator, femoral, pudendal, and inferior hypogastric nerves and the inferior hypogastric and lumbosacral plexuses. Although it is thought to be rare, the true incidence of nerve involvement in endometriosis is not known. Symptoms of neural involvement include pain, weakness, numbness, incontinence, and paraplegia and may be constant or cyclic (catamenial). Early diagnosis of neural involvement in endometriosis is important to prevent irreversible nerve damage and chronic sensorimotor neuropathy. Evidence of irreversible damage can also be seen at MRI, and radiologists should evaluate pelvic nerves that are commonly involved in endometriosis in their search pattern and report template to ensure that this information is incorporated into treatment planning.

High-resolution nerve ultrasound and corneal confocal microscopy in taxane-induced polyneuropathy.

BACKGROUND AND PURPOSE: The role of high-resolution nerve ultrasound (HRUS) and corneal confocal microscopy (CCM) in the early detection of taxane-induced polyneuropathy (TIPN) is unclear. The present prospective longitudinal controlled observational pilot study estimates the role of HRUS and CCM in the early diagnosis of TIPN in breast cancer patients. METHODS: Fifteen breast cancer patients receiving paclitaxel and 15 healthy age matched controls were included. Visits before and 3 weeks, 8 weeks and 6 months after treatment included clinical examination, the total neuropathy score, nerve conduction studies (NCS), monocular CCM including corneal nerve fibre length, density and branching and HRUS of bilateral median, ulnar, radial, tibial, peroneal and sural nerves. Patients were compared between different visits and to healthy controls. RESULTS: Total neuropathy score increased from 2.2 at baseline to 5.8 (p < 0.001) at week 8. NCS showed a decreased sensory amplitude in the sural, radial, ulnar and median nerve after 6 months (p < 0.001). HRUS revealed a significant increase of cross-sectional area in the sural nerve (p = 0.004), the median nerve (p = 0.003) at the carpal tunnel and the ulnar nerve in the forearm (p = 0.006) after 6 months. CCM showed no changes at different visits. CONCLUSIONS: Corneal confocal microscopy and HRUS do not detect early signs of TIPN during the paclitaxel treatment period. HRUS and NCS might detect congruent signs of an axonal, predominantly sensory polyneuropathy after 6 months. The clinical examination remains the most sensitive tool in the early detection of TIPN in breast cancer patients.

The role of neuromuscular ultrasound in diagnostics of peripheral neuropathies induced by cytostatic agents or immunotherapies.

A relevant number of cancer patients who receive potentially neurotoxic cytostatic agents develop a chemotherapy-induced peripheral neuropathy over time. Moreover, the increasing use of immunotherapies and targeted agents leads to a raising awareness of treatment-associated peripheral neurotoxicity, e.g., axonal and demyelinating neuropathies such as Guillain-Barré-like syndromes. To date, the differentiation of these phenomena from concurrent neurological co-morbidities or (para-)neoplastic nerve affection as well as their longitudinal monitoring remain challenging. Neuromuscular ultrasound (NMUS) is an established diagnostic tool for peripheral neuropathies. Performed by specialized neurologists, it completes clinical and neurophysiological diagnostics especially in differentiation of axonal and demyelinating neuropathies. No generally approved biomarkers of treatment-induced peripheral neurotoxicity have been established so far. NMUS might significantly extend the repertoire of diagnostic and neuromonitoring methods in this growing patient group in short term. In this article, we present enlargements of the dorsal roots both in cytostatic and in immunotherapy-induced neurotoxicity for the first time. We discuss related literature regarding new integrative applications of NMUS for cancer patients by reference to two representative case studies. Moreover, we demonstrate the integration of NMUS in a diagnostic algorithm for suspected peripheral neurotoxicity independently of a certain cancer treatment regimen emphasizing the emerging potential of NMUS for clinical routine in this interdisciplinary field and prospective clinical trials.

Exploration of Neurofilament Light Chain and Nerve Ultrasound in Leprotic Neuropathy.

OBJECTIVES: To explore neurofilament light chain (NfL) levels in leprotic neuropathy compared to controls, and to determine if the changes correlate with ultrasonographic nerve findings. METHODS: Individuals with leprosy with signs or symptoms suggestive of peripheral nerve involvement were recruited. They were evaluated by clinical examination, functional scores, laboratory assessments (including NfL), nerve conduction studies (NCS), and ultrasound. Ultrasound was conducted in bilateral median, ulnar, tibial, fibular, sural, and vagus nerves as well as cervical roots 5 and 6. Results were compared to age, sex, and body mass index matched healthy controls. RESULTS: A total of 320 nerves from 20 patients and 480 nerves from 30 controls were evaluated. NfL was significantly elevated in those with leprosy with a mean and standard deviation of 7.50 + 2.83 compared with 3.42 + 1.18 in controls (P < .001). Ultrasound showed focal enlargement of the nerves, particularly at entrapment sites. Additionally, there were noticeable changes in neural Doppler signal, echogenicity, and epineural thickness among the measured nerve sites. NfL levels in those with leprosy correlated closely with nerve cross-sectional area at all sites (P < .05). Functional and clinical assessment scores correlated with NfL and sonographic cross-sectional area as well (P ≤ .05). CONCLUSIONS: NfL is elevated in leprotic neuropathy. Ultrasound showed specific morphological changes in individuals with leprosy, and nerve enlargement correlated with NfL levels. Thus, both modalities may be useful for the diagnosis, prognosis, and disease monitoring in those with leprotic neuropathy, and further investigations are warranted.

Corneal confocal microscopy in small and mixed fiber neuropathy-Comparison with skin biopsy and cold detection in a large prospective cohort.

BACKGROUND AND AIMS: The diagnosis of small fiber neuropathy (SFN) is supported by reduced intraepidermal nerve fiber density (IENFD). The noninvasive method corneal confocal microscopy (CCM) has the potential to be a practical alternative. We aimed to estimate the diagnostic accuracy of CCM compared with IENFD and cold detection thresholds (CDT) in SFN and mixed fiber neuropathy (MFN). METHODS: CCM was performed in an unselected prospective cohort of patients with a clinical suspicion of polyneuropathy. Predefined criteria were used to classify SFN and MFN. Neuropathy scores, including the Utah early neuropathy scale (UENS), were used to describe severity. Patients with established other diagnoses were used for diagnostic specificity calculations. RESULTS: Data were taken from 680 patients, of which 244 had SFN or MFN. There was no significant difference in sensitivities [95%CI] of CCM (0.44 [0.38-0.51]), IEFND (0.43 [0.36-0.49]), and CDT (0.34 [0.29-0.41]). CCM specificity (0.75 [0.69-0.81]) was lower (p = .044) than for IENFD (0.99 [0.96-1.00]) but not than for CDT (0.81 [0.75-0.86]). The AUCs of the ROC curves of 0.63, 0.63 and 0.74 respectively, was lower for corneal nerve fiber density (p = .0012) and corneal nerve fiber length (p = .0015) compared with IENFD. While UENS correlated significantly with IENFD (p = .0016; R2 = .041) and CDT (p = .0002; R2 = .056), it did not correlate with CCM measures. INTERPRETATION: The diagnostic utility of CCM in SNF and MFN is limited by the low specificity compared with skin biopsy. Further, CCM is less suitable than skin biopsy and CDT as a marker for neuropathy severity.

Neuropathy Score Reporting and Data System (NS-RADS): A Practical Review of MRI-Based Peripheral Neuropathy Assessment.

The Neuropathy Score Reporting and Data System (NS-RADS) is a newly developed MR imaging-based classification that standardizes reporting and multidisciplinary communication for MR imaging diagnosis and follow-up of peripheral neuropathies. NS-RADS classification has shown to be accurate and reliable across different centers, readers' experience levels, and degrees of peripheral neuropathies, which include nerve injury, entrapment, neoplasm, diffuse neuropathy, post-interventional status, and temporal changes in muscle denervation. This article brings a practical review of NS-RADS classification, representative MR cases, and a step-by-step tutorial on how to approach this staging system. Readers can gain knowledge and apply it in their practice, aiming to standardize the communications between specialties and improve patient management.

Peripheral nerve involvement in hereditary spastic paraplegia characterized by quantitative magnetic resonance neurography.

BACKGROUND AND OBJECTIVES: Hereditary spastic paraplegias (HSPs) are heterogenous genetic disorders. While peripheral nerve involvement is frequent in spastic paraplegia 7 (SPG7), the evidence of peripheral nerve involvement in SPG4 is more controversial. We aimed to characterize lower extremity peripheral nerve involvement in SPG4 and SPG7 by quantitative magnetic resonance neurography (MRN). METHODS: Twenty-six HSP patients carrying either the SPG4 or SPG7 mutation and 26 age-/sex-matched healthy controls prospectively underwent high-resolution MRN with large coverage of the sciatic and tibial nerve. Dual-echo turbo-spin-echo sequences with spectral fat-saturation were utilized for T2-relaxometry and morphometric quantification, while two gradient-echo sequences with and without an off-resonance saturation rapid frequency pulse were applied for magnetization transfer contrast (MTC) imaging. HSP patients additionally underwent detailed neurologic and electroneurographic assessments. RESULTS: All microstructural (proton spin density [ρ], T2-relaxation time, magnetization transfer ratio) and morphometric (cross-sectional area) quantitative MRN markers were decreased in SPG4 and SPG7 indicating chronic axonopathy. ρ was superior in differentiating subgroups and identifying subclinical nerve damage in SPG4 and SPG7 without neurophysiologic signs of polyneuropathy. MRN markers correlated well with clinical scores and electroneurographic results. CONCLUSIONS: MRN characterizes peripheral nerve involvement in SPG4 and SPG7 as a neuropathy with predominant axonal loss. Evidence of peripheral nerve involvement in SPG4 and SPG7, even without electroneurographically manifest polyneuropathy, and the good correlation of MRN markers with clinical measures of disease progression, challenge the traditional view of the existence of HSPs with isolated pyramidal signs and suggest MRN markers as potential progression biomarkers in HSP.

New observations on minifascicular neuropathy with sex-dependent gonadal dysgenesis: a case series with nerve ultrasound assessment.

BACKGROUND: Gonadal dysgenesis with minifascicular neuropathy (GDMN) is a rare autosomal recessive condition associated with biallelic DHH pathogenic variants. In 46, XY individuals, this disorder is characterized by an association of minifascicular neuropathy (MFN) and gonadal dysgenesis, while in 46, XX subjects only the neuropathic phenotype is present. Very few patients with GDMN have been reported so far. We describe four patients with MFN due to a novel DHH likely pathogenic homozygous variant and the results of nerve ultrasound assessment. METHODS: This retrospective observational study included 4 individuals from 2 unrelated Brazilian families evaluated for severe peripheral neuropathy. Genetic diagnosis was performed with a peripheral neuropathy next-generation sequencing (NGS) panel based on whole exome sequencing focused analysis that included a control SRY probe to confirm genetic sex. Clinical characterization, nerve conduction velocity studies, and high-resolution ultrasound nerve evaluation were performed in all subjects. RESULTS: Molecular analysis disclosed in all subjects the homozygous DHH variant p.(Leu335Pro). Patients had a striking phenotype, with marked trophic changes of extremities, sensory ataxia, and distal anesthesia due to a sensory-motor demyelinating polyneuropathy. One 46, XY phenotypically female individual had gonadal dysgenesis. High-resolution nerve ultrasound showed typical minifascicular formation and increased nerve area in at least one of the nerves assessed in all patients. CONCLUSION: Gonadal dysgenesis with minifascicular neuropathy is a severe autosomal recessive neuropathy characterized by trophic alterations in limbs, sensory ataxia, and distal anesthesia. Nerve ultrasound studies are very suggestive of this condition and may help to avoid invasive nerve biopsies.

Parsonage-Turner syndrome following monkeypox infection and vaccination.

Beginning in May 2022, monkeypox infection and vaccination rates dramatically increased due to a worldwide outbreak. This case highlights magnetic resonance (MR) neurography findings in an individual who developed Parsonage-Turner syndrome (PTS) 5 days after monkeypox symptom onset and 12 days after receiving the JYNNEOS vaccination. MR neurography of the patient's left suprascapular nerve demonstrated intrinsic hourglass-like constrictions, a characteristic finding of peripheral nerves involved in PTS. Other viral infections and vaccinations are well-documented triggers of PTS, an underrecognized peripheral neuropathy that is thought to be immune-mediated and results in severe upper extremity pain and weakness. The close temporal relationship between monkeypox infection and vaccination, and PTS onset, in this case, suggests a causal relationship and marks the first known report of peripheral neuropathy associated with monkeypox.

Imaging of the Peripheral Nerves of the Lower Extremity.

Continued advancements in magnetic resonance (MR) neurography and ultrasound have made both indispensable tools for the workup of peripheral neuropathy. Ultrasound provides high spatial resolution of superficial nerves, and techniques such as "sonopalpation" and dynamic maneuvers can improve accuracy. Superior soft tissue contrast, ability to evaluate both superficial and deep nerves with similar high resolution, and reliable characterization of denervation are strengths of MR neurography. Nevertheless, familiarity with normal anatomy, anatomic variants, and common sites of nerve entrapment is essential for radiologists to use both MR neurography and ultrasound effectively.

Ultrasound-based Neuropathy Diagnosis in COVID-19 Patients in Post-intensive Care Rehabilitation Settings: A Retrospective Observational Study.

OBJECTIVES: Using ultrasound (US) scanning to examine the correlation between increase of common fibular nerve's (CFN) cross sectional area (CSA) and functional impairment of foot dorsiflexor muscles as an early sign of peripheral neuropathy. DESIGN: Retrospective observational study. SETTING: In-patient rehabilitation unit between November 2020 and July 2021. PARTICIPANTS: Twenty-six inpatients who underwent prolonged hospitalization in intensive care units (ICUs) and were diagnosed with critical illness myopathy and polyneuropathy after SARS-COV-2 infection (N=26). Physical examination and US scanning of the CFN and EMG/ENG were carried out on each patient. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): CFN's CSA at the peroneal head. RESULTS: We verified a significant increase in the CSA of the CFN measured at the peroneal head in more than 90% of the nerves tested. A cut off value of CFN's CSA of 0.20 cm was used to identify pathologic nerves. No correlations with other variables (body mass index, ICU days) were found. CONCLUSION: US scanning of the CFN appears to be an early and specific test in the evaluation of CPN's abnormalities in post COVID-19 patients. US scanning is a reproducible, cost effective, safe, and easily administered bedside tool to diagnose a loss of motor function when abnormalities in peripheral nerves are present.

Aging Muscles, Myositis, Pain, and Peripheral Neuropathies: PET Manifestations in the Elderly.

Advancing age significantly affects the structural and functional characteristics of organs and tissues, including the peripheral nervous system (PNS) and musculoskeletal system. PET molecular imaging systems offer the ability to assess the metabolic and quantitative effects due to nerve and muscle injuries, which has the potential to impact clinical management of aged subjects. Here, we aim to describe some features of molecular imaging PET systems using different tracers and methods of imaging in musculoskeletal disorders and peripheral neuropathies commonly seen in elderly patients.

Neuroimaging reveals a potential brain-based pre-existing mechanism that confers vulnerability to development of chronic painful chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition impacting 30% of cancer survivors. This study is the first to explore whether a brain-based vulnerability to chronic sensory CIPN exists. METHODS: This prospective, multicentre cohort study recruited from three sites across Scotland. Brain functional MRI (fMRI) scans (3 Tesla) were carried out on chemotherapy naïve patients at a single fMRI centre in Edinburgh, Scotland. Nociceptive stimuli (with a 256 mN monofilament) were administered during the fMRI. Development of chronic sensory/painful CIPN (CIPN+) was determined based upon European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 changes conducted 9 months after chemotherapy, and imaging data analysed using standard software. RESULTS: Of 30 patients recruited (two lung, nine gynaecological, and 19 colorectal malignancies), data from 20 patients at 9 months after chemotherapy was available for analysis. Twelve were classified as CIPN+ (mean age, 63.2[9.6] yr, 9.6; six female), eight as CIPN- (mean age 62.9 [SD 5.5] yr, four female). In response to punctate stimulation, group contrast analysis showed that CIPN+ compared with CIPN- had robust activity in sensory, motor, attentional, and affective brain regions. An a priori chosen region-of-interest analysis focusing on the periaqueductal grey, an area hypothesised as relevant for developing CIPN+, showed significantly increased responses in CIPN- compared with CIPN+ patients. No difference in subcortical volumes between CIPN+ and CIPN- patients was detected. CONCLUSIONS: Before administration of any chemotherapy or appearance of CIPN symptoms, we observed altered patterns of brain activity in response to nociceptive stimulation in patients who later developed chronic sensory CIPN. This suggests the possibility of a pre-existing vulnerability to developing CIPN centred on brainstem regions of the descending pain modulatory system.

High-frequency Ultrasonography of the Digital and Palmar Nerve Branches of the Hand in Peripheral Nerve Diseases.

Peripheral nerve ultrasound is a well-established imaging technique to evaluate certain peripheral nerve pathologies. However, there is a poor correlation between ultrasound abnormalities of peripheral nerves and electrodiagnostic or clinical evidence of axonal loss. This is a significant limitation of peripheral nerve ultrasound, as many peripheral nerve diseases encountered in clinical settings are related to axonal loss. Furthermore, clinical and electrodiagnostic evidence of axonal loss directly correlates with disability in all peripheral nerve diseases. However, due to the floor effects often encountered in electrodiagnostic studies, these correlations, as well as definitive diagnoses, are often challenging. Thus, imaging techniques that correlate with axonal loss are essential for expanding the utility of peripheral nerve ultrasound as a potential biomarker for peripheral nerve diseases. With new technological advancements and the ever-increasing imaging capabilities of high-frequency ultrasound, the palmar and digital nerve branches of the hand can be imaged with exceptionally high resolution even using point-of-care ultrasound devices. Their superficial and distal-most anatomic locations are ideal for evaluating polyneuropathies, as these branches degenerate earliest during axonal loss. However, no studies have systematically evaluated these nerve branches to determine if they can be reproducibly measured with ultrasound. The current protocol was adapted for the systematic assessment of cross-sectional areas of the median and ulnar nerves in the palmar surface and digits of the hand. This protocol provides reference data for a subset of nerves that demonstrate high intraclass correlation coefficients between three separate ultrasonographers. Finally, as a proof of concept and to demonstrate the clinical applications of this protocol, representative data from individuals with genetically confirmed inherited polyneuropathies are compared with established normative data to examine cross-sectional area differences.

The Value of In Vivo Reflectance Confocal Microscopy as an Assessment Tool in Chemotherapy-Induced Peripheral Neuropathy: A Pilot Study.

BACKGROUND: There is a lack of standardized objective and reliable assessment tools for chemotherapy-induced peripheral neuropathy (CIPN). In vivo reflectance confocal microscopy (RCM) imaging offers a non-invasive method to identify peripheral neuropathy markers, namely Meissner's corpuscles (MC). This study investigated the feasibility and value of RCM in CIPN. PATIENTS AND METHODS: Reflectance confocal microscopy was performed on the fingertip to evaluate MC density in 45 healthy controls and 9 patients with cancer (prior, during, and post-chemotherapy). Quantification was completed by 2 reviewers (one blinded), with maximum MC count/3 × 3 mm image reported. Quantitative Sensory Testing (QST; thermal and mechanical detection thresholds), Grooved pegboard test, and patient-reported outcomes measures (PROMS) were conducted for comparison. RESULTS: In controls (25 females, 20 males; 24-81 years), females exhibited greater mean MC density compared with males (49.9 ± 7.1 vs 30.9 ± 4.2 MC/3 × 3 mm; P = .03). Differences existed across age by decade (P < .0001). Meissner's corpuscle density was correlated with mechanical detection (ρ = -0.51), warm detection (ρ = -0.47), cold pain (ρ = 0.49) thresholds (P < .01); and completion time on the Grooved pegboard test in both hands (P ≤ .02). At baseline, patients had reduced MC density vs age and gender-matched controls (P = .03). Longitudinal assessment of MC density revealed significant relationships with QST and PROMS. Inter-rater reliability of MC count showed an intraclass correlation of 0.96 (P < .0001). CONCLUSIONS: The findings support the clinical utility of RCM in CIPN as it provides meaningful markers of sensory nerve dysfunction. Novel, prospective assessment demonstrated the ability to detect subclinical deficits in patients at risk of CIPN and potential to monitor neuropathy progression.

Ultrasonographic Evaluation of Peripheral Nerves: Technical Considerations.

Advances in ultrasonographic (US) technology featuring high-resolution transducers have revolutionized US over recent years as a modality increasingly used in the evaluation of musculoskeletal structures and peripheral nerves. A wide variety of nerve pathologies can be detected, such as neoplastic and tumorlike lesions, entrapment syndromes, posttraumatic injuries, and inflammatory conditions. US can serve as an imaging tool for guiding percutaneous treatments, such as injection therapies or hydrodissection, and assist with perioperative nerve marking and visualization of peripheral nerves in the operating room. This article describes the normal US appearance of peripheral nerves, US imaging techniques, common peripheral nerve pathologies, and interventional applications.

Entrapment Neuropathies of the Shoulder.

Entrapment neuropathies of the shoulder most commonly involve the suprascapular or axillary nerves, and they primarily affect the younger, athletic patient population. The extremes of shoulder mobility required for competitive overhead athletes, particularly in the position of abduction and external rotation, place this cohort at particular risk. Anatomically, the suprascapular nerve is most prone to entrapment at the level of the suprascapular or spinoglenoid notch; the axillary nerve is most prone to entrapment as it traverses the confines of the quadrilateral space.Radiographs should be ordered as a primary imaging study to evaluate for obvious pathology occurring along the course of the nerves or for pathology predisposing the patient to nerve injury. Magnetic resonance imaging plays a role in not only identifying any mass-compressing lesion along the course of the nerve, but also in identifying muscle signal changes typical for denervation and/or fatty atrophy in the distribution of the involved nerve.

Imaging of Entrapment Neuropathies in the Ankle.

Entrapment neuropathies of the ankle and foot pose a major diagnostic challenge and thus remain underdiagnosed. Recent advancements in imaging modalities, including magnetic resonance neurography (MRN), have resulted in considerable improvement in the anatomical localization and identification of pathologies leading to nerve entrapment. MRN supplements clinical examination and electrophysiologic studies in the diagnosis of neuropathies, aids in assessing disease severity, and helps formulate management strategies. A comprehensive understanding of the anatomy and imaging features of the ankle is essential to diagnose and manage entrapment neuropathies accurately. Advancements in imaging and their appropriate utilization will ultimately lead to better diagnoses and improved patient outcomes.

Corneal confocal microscopy to detect early immune-mediated small nerve fibre loss in AL amyloidosis.

OBJECTIVE: Light chain (AL) amyloidosis is a life-threatening disorder characterised by extracellular deposition of amyloid leading to dysfunction of multiple organs. Peripheral nerve involvement, particularly small fibre neuropathy, may be associated with poorer survival. Corneal confocal microscopy (CCM) is a rapid and non-invasive imaging technique to quantify corneal small nerve fibres and immune cells in vivo. We aimed to evaluate CCM as a tool for early diagnosis of peripheral nerve involvement in AL amyloidosis. METHODS: CCM and nerve conduction studies (NCS) were undertaken in 21 newly diagnosed, treatment-naïve AL amyloidosis patients and 21 age- and sex-matched healthy controls. Corneal nerve fibre density (CNFD), corneal nerve branch density and fibre length, and cell infiltrates were quantified in the sub-basal layer of the cornea. RESULTS: There was a significant reduction in CNFD and nerve fibre length, even without large fibre affection and an increase in cell density, particularly around corneal nerve fibres in patients with AL amyloidosis compared to controls. Additionally, cell infiltration correlated with reduced nerve fibre density in patients with AL amyloidosis, but reduced CNFD did not correlate with laboratory parameters of organ dysfunction. INTERPRETATION: Our study is the first to show that CCM allows rapid non-invasive identification of early small nerve fibre damage associated with immune cell infiltration in patients with AL amyloidosis. CCM detects peripheral nerve involvement more sensitively than NCS.