Nerve cross-sectional area from childhood to old age: A high-resolution nerve ultrasound study.

BACKGROUND AND PURPOSE: Nerve cross-sectional area (CSA) is not constant over the human lifespan. The relationship between an increasing CSA and age has been described as a linear positive correlation, but few studies have found a linear decrease in nerve size with older age. The aim of the present study was to analyze the development of nerve CSA in a healthy population from early childhood to old age using high-resolution ultrasound. METHODS: The median, ulnar, radial and sural nerves were examined bilaterally at 18 nerve sites in 110 healthy children, adolescents and adults aged between 2 and 98 years. The CSA of every nerve site was evaluated separately and in different age groups. The correlation of CSA with age, height and weight was analyzed in a linear, logarithmic and quadratic model and correlation coefficients were compared in a goodness-of-fit analysis. Models were then adjusted for weight and height. RESULTS: Linear CSA-age correlations showed the lowest correlation coefficients for all nerve sites. An inverted parabolic curve suggesting a quadratic correlation of CSA and age was the best-fitting model. Weight and height had a higher predictive value than age in adjusted models. CONCLUSIONS: There is an increase in nerve size during childhood and adolescence and a trend towards a decrease in old age, suggesting an inverted parabolic curve partly explained by age-related changes in weight and height. Enlarged nerves in elderly individuals should not be attributed to age alone.

Nerve cross-sectional area in advanced uremic neuropathy: A nerve ultrasound pilot study.

BACKGROUND AND PURPOSE: Uremic neuropathy (UN) is a disabling neuropathy in end-stage kidney disease (ESKD) affecting the majority of patients receiving long-term hemodialysis (HD). One previous nerve ultrasound study reported an increased cross-sectional area (CSA) of the median nerve in moderate UN, while another study found enlarged sural nerves in small-fiber polyneuropathy associated with ESKD. The present cohort study aims to analyze bilateral CSA of multiple nerves in UN. METHODS: Ten nondiabetic ESKD patients with UN on HD for at least 2 years and 10 healthy age-matched controls underwent bilateral ultrasound examinations with CSA measurements in 13 arm and leg nerve sites. Nerve conduction studies (NCS) and the total neuropathy score (TNS) were recorded. Pearson's coefficient and the Mann-Whitney U-test were used to analyze correlations and compare groups. RESULTS: ESKD patients presented advanced neuropathic symptoms (mean TNS 15.9). NCS showed significantly reduced motor and sensory amplitudes in the UN group compared to the control group, and a slightly reduced nerve CSA was observed in 5 of 13 nerve sites (p < .05); the other nerve sites were not enlarged. Sural nerve CSA (p < .05) and sensory amplitude (p < .01) were negatively correlated with the TNS. CONCLUSIONS: Nerve enlargement was not observed in the present study in advanced UN. A reduced nerve CSA observed in the sural nerve suggests an axonal loss associated with long-term HD in ESKD. During clinical workup of an acute disease of the peripheral nervous system in ESKD patients, nerve enlargement might be attributable to other causes than chronic UN.

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.

Nerve ultrasound reference values in children and adolescents: Echogenicity and influence of anthropometric factors including hand volume.

Background: Nerve cross-sectional area (CSA) reference values in high-resolution ultrasound for children and adolescents are influenced by demographic and anthropometric factors such as age, height and weight. Objectives: The influence of hand volume as an additional morphometric factor was evaluated and nerve echogenicity was analyzed in a prospective cross-sectional study. Methods: CSA were measured in 30 healthy children and adolescents from 2 to 17 years in the median, ulnar, radial, tibial, peroneal and sural nerves. Height, weight, age, handedness and gender were recorded, the volume of the hands was measured using the water displacement method. The intra-nerve CSA variability (INV), left/right ratios and absolute differences were calculated. Age groups were compared by the Kruskal-Wallis test. The influence of demographic factors was analyzed using Spearman correlation and multiple linear regression. Echogenicity and fraction of black were determined for each nerve segment. Results: Nerve CSA values were consistently lower than those reported for adults and correlated in all measured nerve sites with age, height, weight and hand volume. Weight showed the highest correlation coefficient (R = .95) with the best fitting model predicting CSA. Correlation coefficients were higher in a linear than in a logarithmic model. Ratios were stable, the absolute differences increased with age and were significantly different between age groups. Most nerves showed a mixed or hypoechogenic pattern in echogenicity analysis, hyperechogenicity is less frequently observed. Conclusions: Nerve CSA in children and adolescents is lower than in adults and increases proportionally during growth with a constant INV and left/right ratio in different age groups. Weight and age are predominant anthropometric factors predicting nerve size. Hand volume is correlated with nerve size, but does not predict CSA independently. Echogenicity can provide additional information on nerve structure.

Vagus nerve cross-sectional area decreases in Parkinson's disease.

INTRODUCTION: Morphological alterations of the vagus nerve (VN) in Parkinson's disease (PD) are discussed controversially. Several studies reported no difference in VN cross-sectional area (CSA) in PD patients in nerve ultrasound, others found a reduced CSA interpreted as atrophy of the VN and involvement of the dorsal nucleus of VN. METHODS: In a prospective comparative cross-sectional study, CSA of the VN bilaterally and the right ulnar nerve, clinical PD scales, non-motor symptoms and autonomic tests were compared between 49 PD patients and 24 healthy controls. Nerve ultrasound was performed by two independent investigators, patients and controls were compared at Bonferroni corrected p < 0.025 using results of both investigators and averaged results. Blinding included CSA measurements and PD scores, but not PD diagnosis. RESULTS: Bilateral averaged VN CSA was significantly lower in PD patients than in controls (Right VN PD mean 2.70 mm2 SD 0.69, controls 3.30 mm2 SD 0.49, p < 0.001. Left VN PD mean 2.45 mm2 SD 0.57, controls 2.77 mm2 SD 0.46, p = 0.012). No difference was found in the ulnar nerve. There was a weak negative correlation between the right VN CSA and the Unified Parkinson Disease Rating Scale (-0.08 mm2 per 10 points). The area under the receiver operating characteristic curve for the right VN was 0.78 (p < 0.001). CONCLUSION: The present results support the hypothesis of atrophy of the VN in PD. Reduction of VN CSA is a weak marker of disease progression. Nerve ultrasound of the VN might represent a supplementary method in diagnosis of PD.

Prevalence and determinants of pain in chronic inflammatory demyelinating polyneuropathy: Results from the German INHIBIT registry.

BACKGROUND AND PURPOSE: Pain, fatigue and depression in chronic inflammatory demyelinating polyneuropathy (CIDP) are often underestimated, as the focus lies on sensorimotor dysfunction and gait instability. The aim of this study was to investigate their prevalence, characteristics and contribution to disability in a prospective cohort of 84 patients with CIDP. METHODS: Pain, fatigue, depression and quality of life were measured using the Pain Detect Questionnaire, Krupp's Fatigue Severity Scale, Beck Depression Inventory II and the German Short-Form 36 Health Survey. Sensorimotor deficits and disability were assessed using the Inflammatory Neuropathy Cause and Treatment overall disability score, the Rasch-built Overall Disability Scale, the Medical Research Council sum score and the Inflammatory Neuropathy Cause and Treatment sensory sum score. The interrelation between the five factors was assessed using analysis of variance and linear regression analysis. RESULTS: Pain was reported in 62%, mostly of moderate and severe intensity, whereas pain characteristics indicated neuropathic pain (NP) in 29%. Sensory dysfunction was stronger in NP patients compared to pain-free patients (p = 0.001). Pain of any type, especially NP, was associated with more pronounced fatigue symptoms (p = 0.010). Depressive symptoms were more frequent in patients with pain compared to the pain-free patients (61% vs. 33%, p = 0.02) and were more severe and frequent in NP than in non-NP patients (p = 0.005). Patients with pain had a worse physical quality of life than pain-free patients (p = 0.001). CONCLUSION: Pain, depression and fatigue are relevant disability factors in CIDP affecting quality of life. Sensory dysfunction is associated with NP. Therefore, evaluation of CIDP-related disability should include pain and sensory function for adequate monitoring of therapeutic interventions.

Assessment of Operator Reliability in Ultrasound of the Median and Ulnar Nerve Using Bland-Altman Analysis.

Currently, there is no standardized method to evaluate operator reliability in nerve ultrasound. A short prospective protocol using Bland-Altman analysis was developed to assess the level of agreement between operators with different expertise levels. A control rater without experience in nerve ultrasound, three novices after two months of training, an experienced rater with two years of experience, and a reference rater performed blinded ultrasound examinations of the left median and ulnar nerve in 42 nerve sites in healthy volunteers. The precision of Bland-Altman agreement analysis was tested using the Preiss-Fisher procedure. Intraclass correlation coefficients (ICC), coefficients of variation, and Bland-Altman limits of agreement were calculated. The sample size calculation and Preiss-Fisher procedure showed a sufficient precision of Bland-Altman agreement analysis. Limits of agreement of all trained novices ranged from 2.0 to 2.9 mm2 and were within the test's maximum tolerated difference. Ninety-five percent confidence intervals of limits of agreement revealed a higher precision in the experienced rater's measurements. Operator reliability in nerve ultrasound of the median and ulnar nerve arm nerves can be evaluated with a short prospective controlled protocol using Bland-Altman statistics, allowing a clear distinction between an untrained rater, trained novices after two months of training, and an experienced rater.

Treatment response to cyclophosphamide, rituximab, and bortezomib in chronic immune-mediated sensorimotor neuropathies: a retrospective cohort study.

BACKGROUND: Up to 20% of patients with chronic immune-mediated sensorimotor neuropathies (CIN) do not respond adequately to first-line therapies. However, studies on further treatment are scarce. METHODS: We analyzed retrospectively 200 CIN patients regarding disease characteristics and response to therapy with cyclophosphamide (CYP), rituximab (RTX), and bortezomib (BTZ). Treatment response was defined as improvement or stabilization of inflammatory neuropathy cause and treatment overall disability score (INCAT-ODSS). RESULTS: A total of 48 of 181 patients (26.5%) received therapy with CYP, RTX, or BTZ. The most frequently and first used therapy was CYP (69%). More than 40% of patients needed a second or third treatment. Overall, 71 treatments were applied in 48 patients. The combination of up to all three treatments enhanced the response-rate to 90%. Treatment within 24 months after initial diagnosis resulted in significantly higher response rate than late treatment (79% versus 50 %, p = 0.04, χ 2-test, n = 46) and in lower disability in long-term follow up (INCAT-ODSS 3.8 versus 5.8, p = 0.02, t-test, n = 48). Patients with Lewis-Sumner syndrome (n = 9) and autoantibody mediated neuropathies (n = 13) had excellent response rates after treatment with RTX (90-100%). In contrast, typical chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) showed a response rate of 64% in CYP, 64% in RTX, and 75% in BTZ. CONCLUSION: Treatment with CYP, RTX, or BTZ was effective in this cohort of CIN refractory to first-line treatment. Our data increase evidence for an early use of these therapies. High efficacy of RTX in Lewis-Sumner syndrome in contrast to typical CIDP suggests a distinct pathophysiology.

Nerve Ultrasound Distinguishes Non-Inflammatory Axonal Polyneuropathy From Inflammatory Polyneuropathy With Secondary Axonal Damage.

INTRODUCTION: Chronic inflammatory demyelinating polyneuropathy (CIDP) may have a similar clinical and electrophysiological presentation to non-inflammatory axonal polyneuropathies (NIAPs) when secondary axonal damage occurs. We aimed to investigate if nerve ultrasound can help to differentiate CIDP with additional secondary axonal damage from NIAP. METHODS: In a retrospective analysis, the cross-sectional area (CSA) of the peripheral nerves measured by ultrasound at six suitable nerve sites was compared in 95 patients with CIDP and 82 patients with NIAP. We developed the adjusted Bochum ultrasound score (aBUS) ranging from 0 to 6 resulting from the number of sites with enlarged CSA (median, ulnar, radial, and sural nerve). RESULTS: The mean CSA of patients with CIDP was enlarged at all six nerve sites compared with the mean CSA of patients with NIAP. A total of 21 patients with CIDP did not meet 2010 electrophysiological diagnostic criteria (European Academy of Neurology/Peripheral Nerve Society Guideline, EFNS/PNS criteria) for CIDP at examination timepoint but only in further follow-up, while 25 patients with NIAP fulfilled electrophysiological EFNS/PNS criteria for CIDP as "possible" or "probable" CIDP. To increase diagnostic power, we included aBUS measured by ultrasound in patients classified as "possible" or "probable" resulting in an improved specificity of 94% and a sensitivity of 59%, compared to a specificity of the EFNS/PNS criteria alone of 60% and sensitivity of 78%. CONCLUSION: Using nerve ultrasound and the aBUS as a complementary method to distinguish CIDP from NIAP in case of secondary axonal damage can facilitate the diagnosis of CIDP.