Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that mainly affects the upper and lower motor neurons. Recent sodium ( 23 Na) MRI studies have shown that abnormal sodium concentration is related to neuronal suffering in neurodegenerative conditions.Purpose: To use 23 Na MRI to investigate abnormal sodium concentrations and map their distribution in the brains of study participants with ALS as compared with healthy control subjects. Materials and Methods:Twenty-seven participants with ALS (mean age, 54 years 6 10 [standard deviation], eight women) and 30 healthy control subjects (mean age, 50 years 6 10; 16 women) were prospectively recruited between September 2015 and October 2017 and were examined by using conventional proton MRI and sodium MRI at 3 T. Voxel-based statistical mapping was used to compare quantitative whole-brain total sodium concentration (TSC) maps in participants with ALS with those in control subjects and to localize regions of abnormal elevated TSC. Potential overlap of abnormal elevated TSC with regions of atrophy as detected with 1 H MRI also was investigated. Results:Voxel-based statistical mapping analyses revealed higher sodium concentration in motor regions (bilateral precentral gyri, corticospinal tracts, and the corpus callosum) of participants with ALS (two-sample t test, P , .005; age and sex as covariates). In these regions, mean TSC was higher in participants with ALS (mean, 45.6 mmol/L wet tissue 6 3.2) than in control subjects (mean, 41.8 mmol/L wet tissue 6 2.7; P , .001; Cohen d = 1.28). Brain regions showing higher TSC represented a volume of 15.4 cm 3 that did not overlap with gray matter atrophy occupying a volume of 16.9 cm 3 . Elevated TSC correlated moderately with corticospinal conduction failure assessed with transcranial magnetic stimulation in the right upper limb (Spearman r = 20.57; 95% confidence interval: 20.78, 20.16; P = .005; n = 23). Conclusion:Quantitative 23 Na MRI is sensitive to alterations of brain sodium homeostasis within disease-relevant regions in patients with amyotrophic lateral sclerosis (ALS). This supports further investigation of abnormal sodium concentration as a potential marker of neurodegenerative processes in patients with ALS that could be used as a secondary endpoint in clinical trials.

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BackgroundAmyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disorder. Diffusion magnetic resonance imagining (MRI) studies have consistently showed widespread alterations in both motor and non-motor brain regions. However, connectomics and graph theory based approaches have shown inconsistent results. Hub-centered lesion patterns and their impact on local and large-scale brain networks remain to be established. The objective of this work is to characterize topological properties of structural brain connectivity in ALS using an array of local, global and hub-based network metrics.Materials and MethodsMagnetic resonance imagining data were acquired from 25 patients with ALS and 26 age-matched healthy controls. Structural network graphs were constructed from diffusion tensor MRI. Network-based statistics (NBS) and graph theory metrics were used to compare structural networks without a priori regions of interest.ResultsPatients with ALS exhibited global network alterations with decreased global efficiency (Eglob) (p = 0.03) and a trend of reduced whole brain mean degree (p = 0.05) compared to controls. Six nodes showed significantly decreased mean degree in ALS: left postcentral gyrus, left interparietal and transverse parietal sulcus, left calcarine sulcus, left occipital temporal medial and lingual sulcus, right precentral gyrus and right frontal inferior sulcus (p < 0.01). Hub distribution was comparable between the two groups. There was no selective hub vulnerability or topological reorganization centered on these regions as the hub disruption index (κ) was not significant for the relevant metrics (degree, local efficiency and betweenness centrality). Using NBS, we identified an impaired motor subnetwork of 11 nodes and 10 edges centered on the precentral and the paracentral nodes (p < 0.01). Significant clinical correlations were identified between degree in the frontal area and the disease progression rate of ALS patients (p < 0.01).ConclusionOur study provides evidence that alterations of structural connectivity in ALS are primarily driven by node degree and white matter tract degeneration within an extended network around the precentral and the paracentral areas without hub-centered reorganization.

Background Hereditary transthyretin amyloidosis (ATTRv) is a disabling and life-threatening disease that primarily affects the nervous system and heart. Its kidney involvement has not been systematically studied, particularly in non-V30M mutations, and is not well known to nephrologists. Material and Methods We conducted a retrospective study describing kidney phenotype of all prevalent patients with ATTR mutations, with neurological or cardiac involvement or presymptomatic carriers, followed-up in two university hospitals from the South of France, between June 2011 and June 2021. Results 103 patients were included, among whom 79 were symptomatic and 24 presymptomatic carriers. Patients carried 21 different ATTR mutations, and 54% carried the V30M mutation. After a mean follow up of 7.9 ± 25.7 years, 30.4% of the symptomatic patients had developed chronic kidney disease (CKD), and 20.3% had a urinary protein/creatinine ratio ≥ 0.5 g/g. None of the presymptomatic carriers had CKD or proteinuria. In a multivariate analysis, late onset of symptom (after 60 years), the V122I mutation, and proteinuria were significantly associated with CKD. Median CKD-free survival in symptomatic patients was estimated 81.0 [77.1; 84.9] years. It did not differ between V30M and non-V30M patients, but was lower in patients with the V122I mutation. The average age of CKD onset was 69.3 ± 13.0 years. In one 38-year-old V30M female, who presented a kidney-predominant phenotype, treatment with patisiran resulted in remission of the nephrotic syndrome. Conclusion CKD affects almost one third of patients with symptomatic ATTRv. The role of ATTRv per se in the development of CKD in this population remains to be determined, but some patients may benefit from specific therapies.

Motor unit number index (MUNIX) variation depends on the experience of the operator. A 20% change in MUNIX sum score is significant. MUNIX could be used as a biomarker in the follow-up of neuromuscular disorders. a b s t r a c t Objective: Motor unit number index (MUNIX) is proposed to monitor neuromuscular disorders. Our objective is to determine the intra-individual variability over time of the MUNIX. Methods: In 11 different hospital centres, MUNIX was assessed twice, at least 3 months apart (range 90-360 days), in tibialis anterior (TA), abductor pollicis brevis (APB), abductor digiti minimi (ADM) and deltoid muscles in 118 healthy subjects. MUNIX sum score 2, 3 and 4 were respectively the sum of the MUNIX of the TA and ADM, of the TA, APB and ADM and of the TA, APB, ADM and deltoid muscles. Results: The repeatability of the MUNIX was better for sum scores than for single muscle recordings. The variability of the MUNIX was independent of sex, age, interval between measurements and was lower for experienced than non-experienced operators. The 95th percentile of the coefficient of variability of the MUNIX sum score 2, 3 and 4 were respectively 22%, 18% and 15% for experienced operators. Conclusions: The MUNIX technique must be performed by experienced operators on several muscles to reduce its variability and improve its reliability. Significance: A variation of the MUNIX sum score !20% can be interpreted as a significant change of muscle innervation.

Background and purpose Nerve tissue alterations have rarely been quantified in Charcot–Marie–Tooth type 1A (CMT1A) patients. The aim of the present study was to quantitatively assess the magnetic resonance imaging (MRI) anomalies of the sciatic and tibial nerves in CMT1A disease using quantitative neurography MRI. It was also intended to seek for correlations with clinical variables. Methods Quantitative neurography MRI was used in order to assess differences in nerve volume, proton density and magnetization transfer ratio in the lower limbs of CMT1A patients and healthy controls. Disease severity was evaluated using the Charcot–Marie–Tooth Neuropathy Score version 2, Charcot–Marie–Tooth examination scores and Overall Neuropathy Limitations Scale scores. Electrophysiological measurements were performed in order to assess the compound motor action potential and the Motor Unit Number Index. Clinical impairment was evaluated using muscle strength measurements and Charcot–Marie–Tooth examination scores. Results A total of 32 CMT1A patients were enrolled and compared to 13 healthy subjects. The 3D nerve volume, magnetization transfer ratio and proton density were significantly different in CMT1A patients for the whole sciatic and tibial nerve volume. The sciatic nerve volume was significantly correlated with the whole set of clinical scores whereas no correlation was found between the tibial nerve volume and the clinical scores. Conclusion Nerve injury could be quantified in vivo using quantitative neurography MRI and the corresponding biomarkers were correlated with clinical disability in CMT1A patients. The sensitivity of the selected metrics will have to be assessed through repeated measurements over time during longitudinal studies to evaluate structural nerve changes under treatment.

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