Reassessment of Split-Leg Signs in Amyotrophic Lateral Sclerosis: Differential Involvement of the Extensor Digitorum Brevis and Abductor Hallucis Muscles

Background: The muscle patterns involved in the “split-leg” syndrome of amyotrophic lateral sclerosis (ALS) remains controversial. We sought to evaluate and reassess the pattern of the extensor digitorum brevis (EDB) and the abductor hallucis (AH) muscles' involvement in split-leg syndrome in ALS.Methods: We recruited 60 consecutive patients with ALS and 25 healthy controls (HCs). Compound muscle action potentials (CMAPs) and F-waves were recorded over the EDB and AH muscles in all subjects. For comparison, we classified patients into two categories based on the presence or absence of lower limbs symptoms.Results: The EDB/AH CMAP amplitude ratio was significantly reduced in patients with affected legs (0.33 ± 0.21, P = 0.007), whereas patients with unaffected legs had a ratio similar to that of the HCs. The EDB/AH ratios for the F-wave latencies, mean F-wave amplitude, mean F/M amplitude ratio, and the persistence of the total repeater F-wave shapes (index Freps) of the EDB-AH, were significantly increased in the affected leg group, whereas the EDB/AH ratio for F-wave persistence was significantly reduced. These findings indicated a greater loss of lower motor neurons (LMNs) innervating the EDB and dysfunction of spinal motoneurons innervating the EDB. In the unaffected leg group, the EDB, but not the AH, F-wave latencies, mean and maximal F/M amplitude ratios, and index Freps were significantly altered. Receiver operating characteristic curve analysis suggested that the EDB F-wave latencies, mean F/M amplitude ratios, and index Freqs (area under the curve [AUC] > 0.8) more strongly differentiated patients with ALS from the HCs compared to the EDB/AH CMAP amplitude ratio (AUC = 0.61). Notably, the EDB maximal F-wave latency and index Freqs reliably differentiated patients with unaffected legs (HCs), with AUCs of 0.83 (95% CI 0.76–0.91) and 0.81 (95% CI 0.72–0.89), sensitivities of 76 and 78%, and specificities of 76 and 78%, respectively.Conclusions: These results suggest preferential EDB compared to AH involvement in the split-leg syndrome of ALS. The EDB maximal F-wave latency and index Freqs robustly differentiated patients with ALS from HCs, which might facilitate an earlier identification of ALS

Restless Legs Syndrome in Chinese Patients With Sporadic Amyotrophic Lateral Sclerosis

Objective: To evaluate the frequency and clinical features of restless legs syndrome (RLS) in a group of Chinese patients with amyotrophic lateral sclerosis (ALS).Methods: 109 Patients included in this study fulfilled the revised El Escorial diagnostic criteria for clinically definite, probable and lab-supported probable ALS, and a group of 109 control subjects was matched for age and sex to the ALS group. Disease severity was assessed by the revised ALS functional rating scale (ALSFRS-R). The diagnosis of RLS was made according to the criteria of the International RLS Study Group. Other characteristics including sleep quality, excessive daytime sleepiness (EDS), REM sleep behavior disorder (RBD), depression and anxiety were also evaluated in ALS patients.Results: RLS was significantly more frequent in ALS patients than in control subjects (14.6 vs. 0.9%; P < 0.05). Compared to those without RLS, ALS patients with RLS reported a higher frequency of anxiety and EDS. ALS patients with RLS showed more severe legs dysfunction. EDS and legs function scores of the ALSFRS-R were independent factors significantly associated with RLS in ALS patients.Conclusions: Our findings suggest that Chinese ALS patients exhibit a high frequency of RLS symptoms and that these patients may benefit from recognition of the condition and optimized management of its symptoms. Moreover, ALS patients might cause circadian rhythms disturbance and our study further supports that ALS is a heterogeneous disorder involving multiple systems; further studies are needed to confirm these preliminary findings

A comprehensive genome variation map of melon identifies multiple domestication events and loci influencing agronomic traits

Melon is an economically important fruit crop that has been cultivated for thousands of years; however, the genetic basis and history of its domestication still remain largely unknown. Here we report a comprehensive map of the genomic variation in melon derived from the resequencing of 1,175 accessions, which represent the global diversity of the species. Our results suggest that three independent domestication events occurred in melon, two in India and one in Africa. We detected two independent sets of domestication sweeps, resulting in diverse characteristics of the two subspecies melo and agrestis during melon breeding. Genome-wide association studies for 16 agronomic traits identified 208 loci significantly associated with fruit mass, quality and morphological characters. This study sheds light on the domestication history of melon and provides a valuable resource for genomics-assisted breeding of this important crop.This work was supported by funding from the Agricultural Science and Technology Innovation Program (to Yongyang Xu, S.H., Z.Z. and H.W.), the China Agriculture Research System (CARS-25 to Yongyang Xu and H.W.), the Leading Talents of Guangdong Province Program (00201515 to S.H.), the Shenzhen Municipal (The Peacock Plan KQTD2016113010482651 to S.H.), the Dapeng district government, National Natural Science Foundation of China (31772304 to Z.Z.), the Science and Technology Program of Guangdong (2018B020202007 to S.H.), the National Natural Science Foundation of China (31530066 to S.H.), the National Key R&D Program of China (2016YFD0101007 to S.H.), USDA National Institute of Food and Agriculture Specialty Crop Research Initiative (2015-51181-24285 to Z.F.), the European Research Council (ERC-SEXYPARTH to A.B.), the Spanish Ministry of Economy and Competitiveness (AGL2015–64625-C2-1-R to J.G.-M.), Severo Ochoa Programme for Centres of Excellence in R&D 2016–2010 (SEV-2015–0533 to J.G.-M.), the CERCA Programme/Generalitat de Catalunya to J.G.-M. and the German Science Foundation (SPP1991 Taxon-OMICS to H.S.)

A comprehensive genome variation map of melon identifies multiple domestication events and loci influencing agronomic traits

Melon is an economically important fruit crop that has been cultivated for thousands of years; however, the genetic basis and history of its domestication still remain largely unknown. Here we report a comprehensive map of the genomic variation in melon derived from the resequencing of 1,175 accessions, which represent the global diversity of the species. Our results suggest that three independent domestication events occurred in melon, two in India and one in Africa. We detected two independent sets of domestication sweeps, resulting in diverse characteristics of the two subspecies melo and agrestis during melon breeding. Genome-wide association studies for 16 agronomic traits identified 208 loci significantly associated with fruit mass, quality and morphological characters. This study sheds light on the domestication history of melon and provides a valuable resource for genomics-assisted breeding of this important crop.info:eu-repo/semantics/acceptedVersio

Correlation of Creatine Kinase Levels with Clinical Features and Survival in Amyotrophic Lateral Sclerosis

ObjectiveTo evaluate serum creatine kinase (CK) levels of amyotrophic lateral sclerosis (ALS) patients and to explore the relationship between CK levels and the clinical characteristics and survival prognosis of ALS patients.MethodsWe analyzed the CK levels of 185 ALS patients who underwent long-term follow-up. The relationship between CK levels and clinical features including sex, age, disease duration, site of onset, body mass index (BMI), serum creatinine (Cr), and spontaneous electromyographic activity was analyzed by univariate analysis and multiple linear regression. Kaplan–Meier and Cox proportional hazards models were used to explore whether CK levels were independently correlated with survival prognosis of ALS.ResultsBaseline serum CK was raised in 43% of participants. The median CK level was 160 U/L (range: 20–2,574 U/L), and 99% of patients had a baseline serum CK level less than 1,000 U/L. CK levels were significantly higher in male patients than in female patients [204 (169) versus 117 (111) U/L, p < 0.001] and in patients with limb onset ALS than with bulbar onset ALS (p < 0.001). CK levels were also correlated with serum Cr (p = 0.011) and the spontaneous potential score of electromyography (EMG) (p = 0.037) but not correlated with age (p = 0.883), disease duration (p = 0.116), or BMI (p = 0.481). Log CK was independently correlated with survival of ALS patients (HR = 0.457, 95% confidence interval 0.221–0.947, p = 0.035) after adjusting for age, sex, site of onset, serum Cr, and BMI.ConclusionSerum CK levels of ALS patients were correlated with sex, site of onsite, serum Cr, and spontaneous activity in EMG. Serum CK could be an independent prognostic factor for survival of ALS patients