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 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.

【Objective】 To investigate cortical thickness changes in the face-head region of the primary motor cortex (PMC) and its effect on survival in amyotrophy lateral sclerosis (ALS) patients. 【Methods】 A retrospective analysis was performed on 105 ALS patients who underwent head MRI scan at the same time. The A4hf (face-head) region of PMC was used as the region of interest (ROI). According to clinical symptoms, patients were divided into two groups: bulbar involvement and non-bulbar involvement. The differences of clinical features and cortical thickness in ROI were analyzed. According to the symptoms of bulbar palsy, physical examination of nervous system and EMG of tongue muscle, the patients with bulbar palsy were divided into lower motor neuron (LMN), upper motor neuron (UMN) and LMN+UMN groups. The differences of bulbar subgroup score and ROI of cortical thickness were analyzed. Age at onset, body mass index, delayed time of diagnosis, bulbar subgroup score, and ROI cortical thickness were included in survival analysis. 【Results】 ① The ROI cortical thickness was significantly lower in bulbar involvement group than non-bulbar involvement group (-0.198±0.87 vs. 0.235±0.95, P=0.017). ② There were no significant differences in the bulbar subgroup scores or cortical thickness of ROI between LMN, UMN and LMN+UMN groups (P>0.05). ③ Survival analysis showed age of onset (HR=3.296, 95% CI:1.63-6.664, P=0.001), delayed time of diagnosis (HR=0.361, 95% CI:0.184-0.705, P=0.003), bulbar subgroup score (HR 0.389, 95% CI:0.174-0.868, P=0.021), and ZRE_ROI cortical thickness (HR=2.309, 95% CI:1.046-5.096, P=0.038) were independent influencing factors of ALS survival. 【Conclusion】 Cortical thickness in A4hf (face-head) region can more objectively reflect UMN signs of region bulbar. In addition to age of onset and delayed time of diagnosis, bulbar subgroup score and cortical thickness of face-head region are also independent influencing factors, and cortical thinning in face-head region is a protective factor for survival of ALS patients.

【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】 The involvement of upper motor neuron (UMN) degeneration is crucial to the diagnosis of amyotrophic lateral sclerosis (ALS). This study aimed to determine objective and sensitive UMN degeneration markers for an accurate and early diagnosis. 【Methods】 A total of 108 ALS patients and 90 age- and gender-matched control subjects were recruited from ALS Clinic of The First Affiliated Hospital of Xi’an Jiaotong University. The motor homunculus cortex thickness data in MRI were collected from all the participants. The clinical characteristics and UMN clinical examination of bulbar, cervical, thoracic and lumbosacral regions were collected from the ALS patients. 【Results】 Cortical thickness was significantly thinner in the ALS group than in the control group in bilateral head-face-bulbar and upper-limb areas (P<0.05). The cortical thickness of the global UMN positive group was significantly thinner than that of control groups in bilateral head-face-bulbar and upper-limb areas (P<0.05). The cortical thickness of the UMN positive group in the corresponding region was significantly thinner than that of control groups in bilateral head-face-bulbar and upper-limb areas (P<0.05). 【Conclusion】 The thinning of the motor homunculus cortex can be used as an objective marker of UMN involvement in ALS patients in clinical practice.

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.

Amyotrophic lateral sclerosis （ALS） is a neurodegenerative disease with the degeneration of the upper motor neuron （UMN） in the motor cortex， the lower motor neuron （LMN） in the brain stem and spinal cord， which leads to progressive muscle weakness and atrophy. Patients eventually die of respiratory failure， and the survival period of most patients is less than 5 years. At present， the diagnosis of ALS is mainly based on the history， clinical manifestations and electrophysiology. The auxiliary examination is only used to exclude other diseases with similar clinical manifestations. The study of genetics and biomarkers provides an objective reference for the early diagnosis， progress and prognosis evaluation of ALS. This paper mainly introduces the latest progress in research on ALS-related markers in biological field. The discovery of special genetic markers can help to diagnose the disease and evaluate the therapeutic effect of individuals； the identification of molecular biology markers has certain value for the diagnosis and differential diagnosis of diseases， while metabolic markers have certain reference value for the progress of diseases. At the same time， this paper summarizes future research on some prospective biomarkers to be further studied and the direction of their clinical application.

Objective To explore the characteristics and influencing factors of cognitive dysfunction in patients with essential tremor (ET).Methods We recruited ET patients diagnosed by the Department of Neurology of the First Affiliated Hospital of Xi`an Jiaotong University and healthy volunteers who matched the ET patients in age, gender and education level for the study.We recorded all the patients` demographic information, tremor degree, and family history based on the family tree.All the participants were tested by MMSE, MoCA, ADL, HAMD and HAMA.Results There were 88 ET patients and 63 normal subjects included in the study.According to MMSE, 31.82％ of the patients had cognitive dysfunctions, with orientation, short-term memory, calculation ability, language skills, retelling, reading comprehension, three-level command and drawing being significantly lower than those of the healthy volunteers (P<0.01);orientation was the most serious damage in cognitive function domain (K=0.624, S=0.726);three-level command was the least serious damage (K=0.274, S=0.319).According to MoCA, 86.36％ of the ET patients had cognitive dysfunction higher than normal people (P<0.05);visual space and execution, clock drawing task, naming, attention, 100-7, language skills, abstract thinking and orientation were significantly lower than normal people (P<0.01);the most serious damage in cognitive function domain was visual space and execution (K=0.651, S=0.786); the least serious damage cognitive function domain was “100-7” (K=0.406, S=0.484). Education level and age affected cognitive dysfunction (P<0.05). ADL scores showed negative correlation with cognitive function (correlation =－0.375 and －0.383, respectively; P<0.001). After the effects of anxiety and depression were excluded, onset age and tremor grading were correlated with cognitive dysfunction (P<0.05). When the above factors were put into binary Logistic regression model, education level was found to be contributed to the model (P<0.05).Conclusion Patients with ET widely suffer from cognitive impairment. Age, education level, daily life disability, age of onset, and tremor degree classification can affect cognitive dysfunction.

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.