Objective To explore the diagnostic values of electrophysiological studies in localizing ulnar neuropathy at the elbow.Methods Totally 21 patients suspected with ulnar neuropathy at the elbow clinically underwent routine electrodiagnostic tests for the confirmative diagnosis,and contrasted with 30 healthy subjects.Routine electrodiagnostic tests included ulnar motor nerve conduction,ulnar sensory nerve conduction from digit 5 to wrist,ulnar innervated muscle electromyography,and a special test: short-segment nerve conduction study.In order to localize ulnar neuropathy at the elbow,special attention was focused on ulnar motor nerve conduction across the elbow using short-segment nerve conduction study.Results ① Nineteen patients were found ulnar motor nerve conduction slowing across the elbow.② Short-segment ulnar nerve conduction studies showed that most of the lesions were located above or below the medial epicondyle 2-3 cm.③ Abnormal flexor carpi ulnaris muscle electromyography was not found involved in ulnar neuropathy at the elbow.Conclusion Short-segment nerve conduction studies have a high diagnostic value in identifying the site of lesion in ulnar neuropathy at the elbow,and abnormal ulnar digit 5 to wrist sensory nerve conduction and abnormal electromyography finding may aid in diagnosis.

Objective To establish the normative ranges for nerve conduction values of distal compound muscle action potential(CMAP) latency and amplitude and to provide evidence for diagnosing peripheral neuropathy.Methods A total of 245 normal volunteers were recruited,and nerve conduction study was carried out on median nerve,ulnar nerve,tibial nerve and peroneal nerve.The distal latency and amplitude were analyzed.The data collected were tabulated and analyzed based on age,sex and weight in the EXCEL and SPSS systems.Results Gender,weight and sidedness had no effects on CMAP distal latency and amplitude.However,age had a significant effect on CMAP amplitude and median nerve distal latency.This age effect was more obvious for people around 40 years old.Distal latency was prolonged and amplitude was decreased with age increasing.Conclusion It is reasonable and clinically practicable to establish the normative ranges of distal CMAP according to two age groups: above and below 40 years old.

Objective To investigate the influencing factors and reference value of sympathetic skin response (SSR) in healthy adults. Methods SSR was studied in 40 normal subjects,with the waveform and onset latency analyzed. Five of them were treated with different intensities of electrical stimulus to observe the subsequent onset latency. Results ① SSR was present in all the hands and it was also true in all the feet except for one case. The waveforms were biphasic or triphasic in the hands and biphasic or triphasic or monophasic in the feet. ② No significant difference was seen between the left and right sides in amplitude and onset latency. ③ Age,height,weight and gender had no significant influences on onset latency of SSR. ④ The normal value on onset latency in the hands was within 1 664 ms and 2 234 ms in the feet,respectively. ⑤ The electrical stimulus intensity had no obvious effect on onset latency. Conclusion Onset latency is an important parameter in evaluating abnormality while amplitude is only a reference index.

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 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 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 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 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.