ABSTRACT:Objective To evaluate the features and related factors of decremental response in amyotrophic lateral sclerosis (ALS)patients to low-frequency repetitive nerve stimulation (RNS)in proximal nerves.Methods We performed RNS studies in proximal axillary and accessory nerves with recording in deltoid and trapezius mus-cle respectively in 87 ALS patients.Decremental compound muscle action potential (CMAP)and related factors were analyzed prospectively,and abnormal group of decremental response in ALS patients was compared with 39 pa-tients with myasthenia gravis.Results ① Abnormal decremental responses were found in 43.7% and 49.4% of ALS patients with deltoid and trapezius muscle recording respectively.They were found more frequent in trapezius muscle than those of deltoid muscle.② There was no relationship of decremental response with gender,age,onset or course of disease,ALSFRS-r scores,or rate of disease progression in ALS patients.③ There was significant rela-tionship between decremental response and fluctuating muscle weakness.Decremental responses decreased more ob-viously in ALS patients with fluctuating muscle weakness than in those with nonfluctuating muscle weakness.④ Dec-remental responses were greater in patients with myasthenia gravis than that in ALS patients.Conclusion Decre-mental response with proximal muscle recording is not an uncommon feature in ALS patients;therefore,it should not be treated as a criterium to rule out ALS.Abnormal decremental response of trapezius muscle is found more fre-quent than that of deltoid muscle.Decremental response range in patients with myasthenia gravis is significantly lar-ger than that in ALS patients.One should be more careful when diagnosing ALS patients with fluctuating muscle weakness and abnormal decremental response.

Objective: To compare the diagnostic sensitivity of muscles in different regions on electromyography (EMG) to optimize and the muscle selection of needle electromyography in amyotrophic lateral sclerosis (ALS). To compare the diagnostic performance of revised El Escorial criteria (rEEC) and Awaji criteria (AwC) in ALS. Methods: Totally 198 ALS patients were recruited from ALS Clinic of The First Affiliated Hospital of Xi'an Jiaotong University and diagnosed with rEEC and AwC diagnostic criteria. Needle EMG was detected in muscles of bulbar, cervical, thoracal, and lumbosacral regions. Results: The muscle sensitivity in ALS regions (with or without clinical involvement) was consistent with that in the regions without clinical involvement. The diagnostic sensitivity of muscles were presented as follows: tongue (54.7% vs. 39.2%), trapezius (44.2% vs. 30.2%), lower orbicularis oris (33.2% vs. 20.7%), sternocleidomastoid (20% vs. 13.2%) in bulbar region, the first dorsal interosseus (93.8% vs. 77.3%), abductor pollicis brevis (92.8% vs. 72.7%), biceps (82% vs. 50%), deltoid (82% vs. 45.4%) in cervical region, thoracic paraspinal muscle 10 (86.5% vs. 85.3%) and rectus abdominis (49.5% vs. 49.3%) in thoracal region, the tibialis anterior (74.6% vs. 46.3%), and gastrocnemius (53.4% vs. 19.7%) in lumbosacral region. The diagnostic rate at AwC standard (75.3%) was significantly higher than that at rEEG standard (24.2%) (McNemar test P<0.001). Conclusion: The muscles of clinical affected region should be detected first, followed by the non-affected region in clinically suspected ALS. The tongue in bulbar region, the first dorsal interosseus in cervical region, thoracic paraspinal muscle 10 in thoracal region, tibialis anterior in lumbosacral region are recommended to detect in EMG protocol. The AwC criteria are suggested in ALS clinical diagnosis.

Objective To evaluate the disease onset regions and spreading patterns in sporadic amyotrophic lateral sclerosis (ALS)patients and related influencing factors.Methods We performed a prospective analysis of 1 58 ALS patients.The disease-onset was confirmed according to the patients’self-reports,neurological examination results and electromyogram study.We followed up 1 5 1 patients with the second or other affected body regions during the disease progression.Data were analyzed according to the different groups of onset regions.Results 1.In 94.3% (149/1 58)of the patients,the early motor manifestations were focally in the bulbar,upper or lower limbs.2.The region of onset was associated with signs of lower motor neuron (LMN)and upper motor neuron (UMN)involvement (P = 0.000 ).The LMN involvement was more distinctive in patients with bulbar onset (65.4%,1 7/26 )group.Patients with cervical onset more frequently showed pure LMN (47.9%,45/94 )or concomitant UMN (52.1%,49/94)signs in the affected limbs.The highest proportion of UMN and LMN signs in the affected lower limb was found in the lumbar onset (83.8%,31/37 )group.3.Spreading patterns:Rostral to caudal spreading pattern was more frequent in bulbar onset patients.For patients with limb onset,there were significant differences between spreading patterns and disease-onset regions (P =0.04).Circular (31.5%,28/89),horizontal (30.3%,31/89)and vertical (21.3%,1 9/89)spreading patterns were more frequent in cervical onset patients whereas circular (47.2%,1 7/36)spreading patterns were more frequent in lumbar onset patients.4.There was a strong association between the rate of progression and age of disease onset (P =0.01 1).Patients aged over 60 had a faster progression.Conclusion ALS is a focal process at motor axis along the spinal cord and cerebral cortex.Different disease-onset can cause different distribution of UMN and LMN signs.Therefore,special attention should be paid to the signs of disease-onset clinically.ALS does start focally and spreads to adjacent regions.Elder patients have a faster disease progression.

Objective To evaluate the gray matter alterations in amyotrophic lateral sclerosis (ALS)by voxel-based morphometry (VBM),and further analyze the correlation between volume changes of gray matter and clinical characteristics.Methods Twenty-seven non-demented patients with ALS and 27 age and gender matched healthy controls were recruited.FSL-VBM was used to detect whole brain gray matter differences between the two groups.Seven prior ROIs were set to be analyzed,including bilateral precentral gyrus,postcentral gyrus,superior,medial,inferior,middle frontal gyrus,and insular cortex.The mean gray matter density of the ROIs was extracted in order to explore the correlation with several clinical measurements such as disease durations and disease severity scores,by using partial correlation analysis with age as covariates.Results Whole brain analysis showed significant gray matter loss in the left precentral gyrus,superior frontal gyrus and postcentral gyrus (numbers of voxel in clusters were 338,112,127,Z =4.83,4.09,6.42,P ＜0.05,FWE corrected).A prior seven ROIs analysis detected gray matter loss in the left precental gyrus,right precentral gyrus,left postcentral gyrus,superior frontal gyrus and left insular cortex (numbers of voxel in clusters were 1104,34,114,91,107,Z =5.87,3.71,4.26,6.29 and 3.51,P ＜0.05,FWE corrected).No statistical significant correlation between regional gray matter loss and clinical measurements were found.Conclusions Motor and extra-motor gray matter loss are present among patients with ALS,which demonstrates ALS as a multi-system disorder.In contrast to whole brain gray matter analysis,ROI analysis is more sensitive to detect extensive cortical changes.The heterogeneity of disease and sensitivity of method may contribute to the lack of correlation between gray matter volume decrease revealed by VBM and clinical characteristics.

Objective:To observe the utility of event-related potential P300 in diagnosing post-stroke cognitive impairment.Methods:Forty-nine stroke survivors at high risk of cognitive impairment formed the observation group, while 54 healthy volunteers were the control group. General clinical data and Montreal Cognitive Assessment Scale (MoCA) scores were compiled for all of the subjects, and the two groups′ P300 latencies, amplitudes and mean reaction times (MRTs) were compared. A total MoCA score <26 (corrected for education level) was taken as the diagnostic criterion for cognitive impairment. The receiver operating characteristics (ROC) curve was employed to analyze the diagnostic efficacy of P300 for post-stroke cognitive impairment and determine the diagnostic cutoff.Results:(1) The average MoCA score, P300 latency and P300 MRT of the observation group were all significantly different from the control group′s averages. There was, however, no significant difference between the two groups′ median P300 amplitudes. (2) According to the ROC curve analysis, the diagnostic limit of P300 latency was 376.50ms. With the area under the curve 0.795, sensitivity was 70.8% and specificity was 78.9%. The diagnosis cut-off value of P300 MRT was 423.35ms, with the area under the curve 0.695, giving a sensitivity of 80.0% and a specificity of 52.6%.Conclusions:Event-related potential P300 has useful efficacy in diagnosing post-stroke cognitive impairment.

Objective:To evaluate changes of large-scale motor and cognition related networks′ function in patients with amyotrophic lateral sclerosis (ALS) and their relationship with corresponding clinical symptoms using independent component analysis combined with dual regression.Methods:Forty-six ALS patients (ALS group) who were treated in the First Affiliated Hospital of Xi′an Jiaotong University from January 2014 to June 2016 were prospectively collected, and 40 gender- and age-matched normal controls (control group) were recruited. All the participants completed the motor and multi-dimensional cognitive function evaluation[including Mini-mental State Examination (MMSE), Montreal Cognitive Assessment (MoCa), Semantic Fluency (SVF), Phonological Fluency (PVF), Digital Span Forward (DS_F), Digital Span backward (DS_B), frontal assessment battery (FAB), Wisconsin Card Sorting Test (WCST) for classification accuracy, classification error, persistent response classification, persistent error response classification, non-persistent error classification and Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA)]. The resting-state MRI data of all subjects were collected, and independent component analysis was carried out with multivariate interpretation linear optimization independent component decomposition. Dual regression analysis was performed to compare network differences between groups based on voxel level in sensorimotor network (SMN), default mode network (DMN) and frontal-parietal control network (FPCN). Multivariate covariance analysis was used to evaluate the differences of different cognitive function indexes between ALS group and normal control group, the comparison of brain network differences between the two groups was performed by nonparametric permutation test, corrected by family-wise error (FWE), P<0.008 as the statistical threshold; partial correlation and multiple linear regression were used to evaluate the relationship between changes in functional connectivity of different brain regions and cognitive functions. Results:The scores of MMSE, MoCa, SVF, PVF, DS_B, and classification accuracy were lower, while the number of error classifications, the non-persistent error classifications, HAMD and HAMA scores were higher in patients with ALS group than those in control group ( P<0.05). After adjusting for gender and age, there was no significant difference in the SMN between ALS group and control group (FWE correction, P>0.008). Compared with control group, patients with ALS showed increased functional connectivity in the left ventromedial prefrontal cortex (vmPFC) of the DMN, and decreased functional connectivity in the right anterior cingulate gyrus (ACC), the right posterior cingulate gyrus, the left inferior parietal lobule and the left inferior temporal gyrus of the FPCN (FWE correction, P<0.008). Increased functional connectivity of the vmPFC in ALS patients was negatively correlated with MoCa score ( r=-0.565, P<0.001), FAB score ( r=-0.373, P=0.015) and the classification accuracy of WCST ( r=-0.478, P=0.002), SVF ( r=-0.458, P=0.002) scores, and was positively correlated with the number of error classifications and HAMA scores ( r=0.416, P=0.007; r=0.388, P=0.011). Decreased functional connectivity were detected in multiple brain regions of FPCN, and the functional connectivity of the ACC was positively correlated with the DS_F ( r=0.341, P=0.027) and MMSE ( r=0.351, P=0.023). The effect of increased vmPFC functional connectivity accounted for 49.6% changes on MoCa score; 35.2% and 34.2% for FAB and HAMA respectively. While the impact of increased functional connectivity in the vmPFC was less than 30% on classification accuracy, classification error of WCST and SVF. The reduced functional connectivity in the ACC accounted for 37.7% impact on the DS_F score. Conclusions:Large-scale brain network changes are dominated by the frontotemporal core brain regions in ALS patients. DMN and FPCN network changes are closely related to the clinical cognitive performance of ALS patients.

Objective Amyotrophic lateral sclerosis(ALS)is a progressive and fatal neurodegenerative disease.Mutations in the Cu/Zn superoxide dismutase 1 gene(SOD1)have been identified as the cause of familial ALS.Sequencing the SOD1 gene may be helpful for patients with a suspected family history of ALS.This article reports for the first time a case of amyotrophic lateral sclerosis with SOD1-p.A5S mutation in Han Chinese and summarizes its clinical characteristics.Method and Results This is the first report on Chinese Han of ALS with SOD1-p.A5S mutation and review of relevant case literature to summarize its clinical characteristics.The study case is a 34-year-old male who was admitted to the Neurology Department of The First Affiliated Hospital of Xi'an Jiaotong University with a complaint of"weakness in both lower limbs for 2 years,worsening with both hands for 6 months".The main clinical manifestations were progressive limb weakness,no swallowing difficulties or cognitive impairment.Further improvement of routine examinations and electromyography after admission were made to rule out other diagnoses,and genetic testing was conducted.Based on the patient's typical clinical manifestations and evidence of involvement of lower motor neurons in the cervical,thoracic,and lumbar spinal cord areas indicated by electromyography,other diagnoses and characteristic gene testing results were reasonably excluded,and ALS was diagnosed.The genetic testing results indicated that the patient had a heterozygous mutation in SOD1 exon 1,c.13G＞T(p.A5S),and his mother had a suspicious medical history but died without genetic verification.After discharge,the follow-up period lasted until August 21,2022,with a total of 38 months and a course of 62 months.Further review of the clinical characteristics of other patients with the same site mutation reported in the literature reveals that the progress of this patient with the mutation was slower than that of other patients with the same site mutation reported in the literature.Conclusion This study shows that gene sequencing is a powerful tool for diagnosing familial ALS.The mutation of c.13G＞T(p.A5S)in exon 1 of SOD1 is a rare pathogenic variation.The progress of patients with this subtype is slow,which further indicates that gene detection has important value in the diagnosis and prognosis of ALS.

【Objective】 To investigate changes in thalamus structure and function and their associations with cognitive impairment in patients with amyotrophic lateral sclerosis (ALS). 【Methods】 3D high-resolution structural imaging and resting-state fMRI were applied in 78 ALS patients and 49 healthy volunteers. The shape of the thalamus was assessed using a vortex analysis and functional connectivity between the thalamus subregion and cortex was evaluated by a seed-based correlation analysis. Partial correlation analysis was used to evaluate the correlation between focal thalamus alterations and clinical assessments. 【Results】 Compared with the control group, vertex analysis showed significant atrophy in the prefrontal and temporal subregions of bilateral thalamus in the ALS group. Patients exhibited increased functional connectivity of motor-sensory ROI with the right motor cortex, of temporal ROI with the bilateral lateral occipital cortex, precuneus and right temporal subregion. In contrast, decreased function connectivity was found mainly between temporal ROI and paracingulate gyrus, left dorsomedial prefrontal lobe and left caudate. Partial correlation analysis showed that the functional connectivity of the precuneus, paracingulate cortex, left caudate nucleus and left prefrontal lobe was correlated with multiple cognitive performances. 【Conclusion】 Selective damage of thalamic structure and function in ALS plays an important role in cognitive and behavioral disorders.

【Objective】 To explore the factors affecting Babinski sign in amyotrophic lateral sclerosis (ALS). 【Methods】 We enrolled 262 patients diagnosed with ALS with adequate data in Department of Neurology, The First Affiliated Hospital of Xi’an Jiaotong University from 2015 to 2020. The relationship between the clinical characteristics of patients with positive and negative Babinski sign was analyzed for both sides, respectively. Furthermore, for patients with left or right lower limb weakness complaint, the relationship between Babinski sign and the lower limb involvement characteristics was analyzed. 【Results】 Positive Babinski sign was positively correlated with higher diagnostic category (left correlation coefficient 0.297, P<0.001; right correlation coefficient 0.292, P<0.001). Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score was lower in patients with positive Babinski sign (left P=0.001, right P=0.001); the proportion of complaints of ipsilateral lower limb weakness was higher (left P=0.008, right P=0.038); the positive rate of ipsilateral upper limb Hoffmann sign was higher (left P=0.004, right P=0.002). In patients with complaints of lower limb weakness, positive Babinski sign was positively correlated with better foot dorsiflexor muscle strength (left correlation coefficient 0.207, P=0.021; right correlation coefficient 0.264, P=0.003), and the proportion of ipsilateral tibialis anterior atrophy was lower in positive Babinski sign group (left P<0.001, right P=0.008); the ratio of ipsilateral common peroneal nerve compound muscle action potential (CMAP)/tibial nerve CMAP was different in positive Babinski sign and negative groups (left P=0.008, right P=0.015), which were positively correlated (left correlation coefficient 0.246, P=0.007; right correlation coefficient 0.223, P=0.015). 【Conclusion】 Patients with positive Babinski sign usually have a higher diagnostic category and more extensive clinical involvement. In ALS patients with complaints of lower limb weakness, Babinski sign is more likely to be elicited when the degree of weakness and atrophy of the anterior calf muscles is relatively low.

【Objective】 To explore the characteristics of white matter degeneration in amyotrophic lateral sclerosis (ALS) patients with different onset and spreading patterns by using diffusion tensor imaging (DTI). 【Methods】 We enrolled 86 ALS patients and 44 healthy controls. The patients were divided into bulbar- and spinal-onset subgroups according to their onset site, as well as horizon, vertical, interpose/skip, and caudal-rostral subgroups based on the spreading direction of the involved regions. The white matter fiber tracts corresponding to the motor network were set as the region of interest. We used tract-based spatial statistics to evaluate differences between the above groups and the normal controls, with family-wise error (FWE) correction and P<0.05 as statistical significance. 【Results】 The white matter degeneration of ALS patients with bulbar onset was mainly limited to the corona radiation part of the corticospinal tract, while those with spinal onset showed extensive degeneration of corticospinal tract and corpus callosum Ⅲ area (FWE correction, P<0.05). In patients with horizontal and vertical dissemination, decreased integrity of the entire corticospinal tract was found, with patients in the latter group showed extra degeneration in the Ⅲ part of the corpus callosum. Restricted degeneration of the corticospinal tract within bilateral corona radiata was detected in patients with caudal-rostral and interposed/skip spreading pattens (FWE correction, P<0.05). 【Conclusion】 Different onset and disease spread patterns of ALS patients correspond to divergent brain degeneration patterns. The diagnosis, treatment, and management of ALS should fully consider the heterogeneity of the disease.