Nerve Sonography in Charcot–Marie–Tooth Disease: A Systematic Review and Meta-analysis of 6061 Measured Nerves

Abdelnaby, Ramy; Elgenidy, Anas; Sonbol, Yousef Tarek; Dardeer, Khaled Tarek; Ebrahim, Mohamed Ayman; Maallem, Imene; Youssef, M.; Moawad, Mostafa Hossam El Din; Hassan, Youssef Gamal; Rabie, Salma Adel; Mohammed, Mohammed Khaled; Abdelrhem, Hasnaa Ali Hassan; Mohamed, Khaled Ashraf; Walter, Uwe

doi:10.1016/j.ultrasmedbio.2022.04.220

Cited by 7 publications

(6 citation statements)

References 30 publications

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“…Likely causes of nerve CSA increase are collagen deposition and Schwann cell hyperplasia, which do not necessarily correlate with disease severity as they do not reflect the degree of axonal loss. Nerve CSA was larger than in axonal CMT2K or even in CMT1A, where nerve CSA is known to be enlarged [ 14 ]. The previously reported pair of sisters with a 17 kb deletion of PMP22 , which also led to the exclusion of exon 4, had similar severe early-onset disease, although the older sister appeared somewhat less severely affected than individual B as she was able to walk with orthoses at age 15 [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…Sensitive biomarkers for CMT are in demand in particular due to its slow progression rate [ 13 ]. Ultrasonographic nerve cross-sectional area (CSA) increases because of nerve hypertrophy in CMT1A [ 14 ]. Nerve CSA may reflect clinical severity of CMT1A [ 15 ], but its usefulness as a longitudinal biomarker has been questioned [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Rare PMP22 variants in mild to severe neuropathy uncorrelated to plasma GDF15 or neurofilament light

Palu,

Järvilehto,

Pennonen

et al. 2023

Neurogenetics

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Charcot-Marie-Tooth disease (CMT) is a heterogeneous set of hereditary neuropathies whose genetic causes are not fully understood. Here, we characterize three previously unknown variants in PMP22 and assess their effect on the recently described potential CMT biomarkers’ growth differentiation factor 15 (GDF15) and neurofilament light (NFL): first, a heterozygous PMP22 c.178G > A (p.Glu60Lys) in one mother-son pair with adult-onset mild axonal neuropathy. The variant led to abnormal splicing, confirmed in fibroblasts by reverse transcription PCR. Second, a de novo PMP22 c.35A > C (p.His12Pro), and third, a heterozygous 3.2 kb deletion predicting loss of exon 4. The latter two had severe CMT and ultrasonography showing strong nerve enlargement similar to a previous case of exon 4 loss due to a larger deletion. We further studied patients with PMP22 duplication (CMT1A) finding slightly elevated plasma NFL, as measured by the single molecule array immunoassay (SIMOA). In addition, plasma GDF15, as measured by ELISA, correlated with symptom severity for CMT1A. However, in the severely affected individuals with PMP22 exon 4 deletion or p.His12Pro, these biomarkers were within the range of variability of CMT1A and controls, although they had more pronounced nerve hypertrophy. This study adds p.His12Pro and confirms PMP22 exon 4 deletion as causes of severe CMT, whereas the previously unknown splice variant p.Glu60Lys leads to mild axonal neuropathy. Our results suggest that GDF15 and NFL do not distinguish CMT1A from advanced hypertrophic neuropathy caused by rare PMP22 variants.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rare PMP22 variants in mild to severe neuropathy uncorrelated to plasma GDF15 or neurofilament light

Palu,

Järvilehto,

Pennonen

et al. 2023

Neurogenetics

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“…Over the last decade, HRUS enabled the reliable examination of small nerves like the VN ( 10 ). A reduced VN-CSA was repeatedly measured in neurodegenerative disorders like PD or amyotrophic lateral sclerosis ( 1 , 2 , 12 ), while enlarged VN-CSA was described in inflammatory ( 13 , 16 , 17 ), but also in hereditary neuropathies ( 18 ). The enlarged left VN-CSA in patients with MDD and especially in the subgroup of patients with RDD might be due to a subtle inflammatory edema of the left VN.…”

Section: Discussionmentioning

confidence: 99%

“…The enlarged left VN-CSA in patients with MDD and especially in the subgroup of patients with RDD might be due to a subtle inflammatory edema of the left VN. Other explanations like hereditary or inflammatory polyneuropathies ( 18 ) are unlikely because of the unaffected MNs, and participants with clinical signs of a polyneuropathy in the profound neurological examination were excluded from this study. Compression of nerves can also cause enlarged CSAs, however, during the HRUS examination the VN was visualized over its cervical course and no compression or entrapment was noted.…”

Section: Discussionmentioning

confidence: 99%

Enlarged cross-sectional area of the left vagus nerve in patients with major depressive disorder

Schreiber,

Wozniak,

Scheller

et al. 2023

Front. Psychiatry

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PurposeAutonomic dysfunction and a chronic low-grade inflammation are supposed to play a role in the etiology of major depressive disorder (MDD). The vagus nerves (VN) form a major part of the parasympathetic nervous system and of the gut-brain axis. They are supposed to exert anti-inflammatory and epithelial barrier protective effects in the gut. A reduced vagal activity was described in patients with MDD. We aimed to examine the VN in patients with MDD with high-resolution ultrasound (HRUS) and hypothesized that the cross-sectional area (CSA) and the echogenicity of the VNs were altered in comparison to healthy controls.Materials and methodsThe echogenicity (gray scale mean) and the CSA of the cervical VNs at the level of the thyroid gland and both median nerves were examined with HRUS in 50 patients with MDD and 50 matched healthy controls.ResultsThe left VN-CSA was significantly larger in the MDD group compared to the control group (1.7 ± 0.4 mm2 versus 1.5 ± 0.4 mm2; p = 0.045). The CSA of the right VN and both median nerves (MN) were similar between groups. In MDD subgroup analyses, recurrent depressive disorders were the main contributing factor for the left VN-CSA enlargement. Echogenicity was not altered in the VN and MN between groups.ConclusionThe enlargement of the left VN-CSA in patients with MDD, and especially in these patients with recurrent depressive disorders, might turn out as a promising imaging biomarker. Longitudinal studies are warranted to examine whether the VNs-CSA change in the course of MDD.

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“…This study provides the CSA or diameter of the measured nerves according to anatomic landmarks in children, which can be used to identify nerve enlargement. Further collective studies could attempt to demarcate disease specific cut-offs in comparison with the normal reference values, such as previous studies in adults with Charcot-Marie-Tooth disease and Parkinson disease 31,32 In this study, no potential outliers were identified by conducting a leave-one-out sensitivity analysis. A subgroup analysis showed that the CSA of the peripheral nerves increases with age.…”

Section: Discussionmentioning

confidence: 99%

Sonographic reference values of nerve size in children: A systematic review and meta‐analysis

et al. 2022

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Introduction/Aims Nerve ultrasound is useful in the diagnosis and follow‐up of peripheral nerve disorders in children. The aim of this study was to explore and analyze the current literature on nerve cross‐sectional area (CSA) in healthy children, with the goal of presenting reference values and discussing their implications. Methods We performed a systematic review and meta‐analysis of studies that reported ultrasound measurements of the upper or lower limb nerves in healthy children through a search of Web of Science, PubMed, Embase, and Scopus. Results Sixteen studies with measurements of 10 nerves covering a total of 5149 nerves measured in 823 healthy children (445 boys and 378 girls) were included. Mean nerve CSA increased with age in the median nerve at the middle and lower third of the upper arm, mid‐forearm, and distal wrist crease, the ulnar nerve at the middle third of the upper arm and elbow, the radial nerve at the spiral groove, and the tibial nerve at the popliteal fossa. Growth charts for nerve CSA for different age groups were developed. Discussion This meta‐analysis provides robust reference values for nerve CSA at different sites in children, and this can inform clinical practice and assist in identifying nerve enlargement. Moreover, it identifies the strength and quality of the current published data. We recommend future studies divide their samples into smaller age subgroups and standardize the anatomic site of measurement.

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Nerve Sonography in Charcot–Marie–Tooth Disease: A Systematic Review and Meta-analysis of 6061 Measured Nerves

Cited by 7 publications

References 30 publications

Rare PMP22 variants in mild to severe neuropathy uncorrelated to plasma GDF15 or neurofilament light

Rare PMP22 variants in mild to severe neuropathy uncorrelated to plasma GDF15 or neurofilament light

Enlarged cross-sectional area of the left vagus nerve in patients with major depressive disorder

Sonographic reference values of nerve size in children: A systematic review and meta‐analysis

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