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Hereditary transthyretin amyloidosis (ATTRv, amyloidosis transthyretin variant) encompasses a broad spectrum of clinical manifestations, with polyneuropathy and cardiomyopathy being the most common organ manifestations. In addition, other organ systems such as kidneys, gastrointestinal tract, eyes and brain may be affected. If left untreated, the disease progresses rapidly, leading to significantly reduced quality of life and increased mortality. Early diagnosis is of particular importance, as drug treatment options have been available for a few years., (© 2023. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Hereditary neuropathies are of variable genotype and phenotype. With upcoming therapies, there is urgent need for early disease recognition and outcome measures. High-resolution nerve and muscle ultrasound is a dynamic, non-invasive, well-established tool in the field of inflammatory and traumatic neuropathies. In this study, we defined nerve and muscle ultrasound parameters as recognition and progression markers in 150 patients with genetically confirmed hereditary neuropathies, including Charcot-Marie-Tooth (CMT) disease (CMT1A, n = 55; other CMT1/4, n = 28; axonal CMT, n = 15; CMTX, n = 15), hereditary neuropathy with liability to pressure palsies (HNPP, n = 16), hereditary transthyretin-amyloidosis (ATTRv, n = 14), and Fabry's disease (n = 7). The CMT1A, followed by the CMT1/4 group, had the most homogeneous enlargement of the nerve cross-sectional areas (CSA) in the ultrasound pattern sum (UPSS) and homogeneity score. Entrapment scores were highest in HNPP, ATTRv amyloidosis, and Fabry's disease patients. In demyelinating neuropathies, the CSA correlated inversely with nerve conduction studies. The muscle echo intensity was significantly highest in the clinically most affected muscles, which was independent from the underlying disease cause and correlated with muscle strength and disease duration. Further correlations were seen with combined clinical (CMTES-2) and electrophysiological (CMTNS-2) scores of disease severity. We conclude that nerve ultrasound is a helpful tool to distinguish different types of hereditary neuropathies by pattern recognition, whereas muscle ultrasound is an objective parameter for disease severity. The implementation of neuromuscular ultrasound might enrich diagnostic procedures both in clinical routines and research., (© 2021. The Author(s).)

Differentiation of Guillain-Barré syndrome (GBS) and acute-onset chronic inflammatory demyelinating polyradiculoneuritis (CIDP) might be intricate in early stages. We compared electrodiagnostics (EDx) and nerve ultrasound (NUS) as tools for early distinction and follow-up. NUS and EDx have been performed at first visitation and after 6 months. The nerve conduction study score (NCSS), the ultrasound pattern sum score (UPSS), and clinical scores were used for comparison. Compared with the 33 GBS patients, the 34 CIDP patients (50% with symptoms < 4 weeks) revealed significant nerve enlargement in ultrasound (p < 0.001) except for the roots and vagus, which exhibited increased values in both groups. EDx has no significant differences between both groups except for the A-wave frequency and the sural sparing pattern, which is more frequent in GBS (Fisher's exact p < 0.05). In the latter, particularly, pure sensory nerves were not enlarged in contrast to CIDP, in which those were mostly enlarged (p < 0.001). This ultrasonic sensory sparing pattern (uSSP) in combination with enlarged roots/vagus is the hallmark finding in GBS with sensitivity, specificity, and positive predictive value > 85%, whereas in CIDP, enlarged sensory und multifocally enlarged sensorimotor nerves are key differentiation features to GBS. Increased echointensity of the nerves further arises only in CIDP. After 6 months, in CIDP, the significant nerve enlargement persisted, whereas in GBS, all segments almost normalized. Clinical, ultrasonic, and NCS scores correlated significantly over the time. Enlarged roots/vagus in combination with uSSP might facilitate differentiation of GBS and CIDP in the early stage, and ultrasonic 6-month normalization underlines the diagnosis of GBS in cases of uncertainty. Trial Registration: DRKS-ID 00005253.

As reliable biomarkers of disease activity are lacking, monitoring of therapeutic response in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) remains a challenge. We sought to determine whether nerve ultrasound and electrophysiology scoring could close this gap. In CIDP patients (fulfilling EFNS/PNS criteria), we performed high-resolution nerve ultrasound to determine ultrasound pattern sum scores (UPSS) and predominant echotexture nerve conduction study scores (NCSS) as well as Medical Research Council sum scores (MRCSS) and inflammatory neuropathy cause and treatment disability scores (INCAT) at baseline and after 12 months of standard treatment. We retrospectively correlated ultrasound morphology with nerve histology when available. 72/80 CIDP patients featured multifocal nerve enlargement, and 35/80 were therapy-naïve. At baseline, clinical scores correlated with NCSS (r 2  = 0.397 and r 2  = 0.443, p < 0.01), but not or hardly with UPSS (Medical Research Council sum scores MRCSS r 2  = 0.013, p = 0.332; inflammatory neuropathy cause and treatment disability scores INCAT r 2  = 0.053, p = 0.048). Longitudinal changes in clinical scores, however, correlated significantly with changes in both UPSS and NCSS (r 2  = 0.272-0.414, p < 0.0001). Combining nerve/fascicle size with echointensity and histology at baseline, we noted 3 distinct classes: 1) hypoechoic enlargement, reflecting active inflammation and onion bulbs; 2) nerve enlargement with additional hyperechogenic fascicles/perifascicular tissue in > 50% of measured segments, possibly reflecting axonal degeneration; and 3) almost no enlargement, reflecting "burned-out" or "cured" disease without active inflammation. Clinical improvement after 12 months was best in patients with pattern 1 (up to 75% vs up to 43% in pattern 2/3, Fisher's exact test p < 0.05). Nerve ultrasound has additional value not only for diagnosis, but also for classification of disease state and may predict treatment response.