Application Of Neuromuscular Ultrasonography In Motor Neuron Disease And Its Differential Diagnosis

Part 1Fasciculations of neuromuscular ultrasound in motor neuron disease and its differential diagnosisBackground:The 2008 Awaji diagnostic criteria emphasized the importance of fasciculations for its early diagnosis.Traditional electrophysiological examinations such as needle electrode electromyography are invasive,and in the early stages of the disease,patients may not meet the diagnostic criteria for involvement of the upper and lower motor neurons in three or more segments of the medulla,neck,chest,and lumbosacral region.Needle electrode electromyography requires at least 70-90 seconds to observe fasciculations,and the scope of observation is limited.The sensitivity of muscle fasciculations is 58-93.5%through ultrasound,and needle electrode electromyography is 17.9%-51.9%.Therefore,observation of fasciculation by ultrasound improves the detection rate compared with needle electrode electromyography,and it can also reduce the patient's pain,so neuromuscular ultrasound can be utilized as a good supplementary tool for traditional electrophysiological examination,providing more clues for clinical diagnosis.Objective and method:In order to explore the application of neuromuscular ultrasound to detect fasciculations in motor neuron disease and its differential diagnosis,prospectively enrolled motor neuron disease and its differential diagnosis,including those diagnosed as possible,probably and definite motor neuron disease according to the Awaji criteria;patients diagnosed with multifocal motor neuropathy according to the 2003 version of the AANEM criteria;Clinically,patients with peripheral neuropathy,myopathy and cervical spondylosis,and patients with lumbar spondylosis or cervical spondylosis or a combination of both which need to be distinguished form MND in the Department of Neurology and Ward of Peking Union Medical College Hospital from December 2017 to August 2019.The general situation and clinical characteristics of patients were collected,and the neuromuscular ultrasound fasciculations observation,segment conduction and electromyography were performed to establish a database.Compare the distribution range of fasciculation,the level of fasciculations and the number of involved muscle groups in different disease groups;analyzed the relationship between the level of fasciculations and the course,onset site,muscle strength,degree of muscle atrophy,and electrophysiological parameters.Results:A total of 57 MND-LMN,83 MND-UMN+LMN,13 MMN,19 patients with cervical spondylosis and lumbar spondylosis,33 PND,7 patients with muscular disease,and 22 healthy control,totaling 234,were included.In the MND-LMN group,a negative correlation was found between the left upper extremity distal extensor muscle strength and the left upper extremity distal extensor fasciculus(r=-0.282,P=0.034).In the MND-UMN+LMN group,each the flexor and extensor group muscle strength was more negative with muscle fasciculations(r=-0.346 to r=-0.505,P<0.001).In addition,this study showed that part of the muscle fasciculations in patients with MND has a negative correlation with the compound muscle action potential,that is,the higher the amplitude,the lower the level of fasciculations.The highest grade of diffuse persistent fasciculation(level 4)in MND-UMN+LMN accounted for 26%.There was a significant statistical difference between the groups(P<0.001).The highest-grade muscle fasciculations did not occur in the cervical spondylosis,lumbar spondylosis,myopathy,and normal groups.The main forms of fasciculations in the MMN,PND,myopathy and cervical spondylosis and lumbar spondylosis groups were also low-grade fasciculation(focal intermittent fasciculation level 1 and multifocal discontinuous fasciculation level 2).Focal intermittent fasciculation occurred in 6.5%of the muscles examined in normal subjects.Among the 22 muscles tested,the specificity of MND with at least 6 muscles was 81.5%,the sensitivity was 87.8%,and the AUC was 0.919(95%CI)0.8-0.9).Patients with MND showed fasciculations in the muscles innervated by the four segments of the medullary,cervical,thoracic,and lumbosacral regions.High-level(ie,diffuse persistent tremor 3 and 4)grade was most common in MND with 13.3%in the proximal upper limb,other groups were common in the low-level fasciculations of the distal limb;cervical spondylosis,lumbar spondylosis,muscle disease,and healthy people did not see any segmental distribution of high-level tremor.Conclusion:Muscle fasciculations,as a manifestation of earlier abnormal excitability of neurons,has special value in motor neuron disease and its differential diagnosis.Patients in MND group are more prone to diffuse persistent fasciculations than patients in the other groups,and are mainly distributed near the proximal limbs.When there are fasciculations in more than 6 groups of muscles,it has significance for the diagnosis of motor neuron disease.Part 2Nerve cross-sectional area in motor neuron disease,multifocal motor neuropathy and peripheral neuropathyBackground:Motor neuron disease(MND)often needs to be distinguished from multifocal motor neuron disease(MMN)and some chronic peripheral neuropathy(PND).At present,the most commonly used auxiliary examination is still neuroelectrophysiological technology,but when electromyography(EMG)still cannot meet the extensive neuronal damage,a certain motor conduction block(CB)or nerve conduction study(NCS)abnormality,the measurement of nerve cross-section area(CSA)by nerve ultrasound can dynamically detect CSA throughout the nerve,providing more clinical evidence for diagnosis.Objective and method:This study aims to apply CSA detection by neuroultrasound to MND,MMN,PND and healthy control,and explore the characteristics of CSA in each group.From December 2017 to September 2019,prospectively enrolled patients with motor neuron disease confirmed by Awaji criteria,multifocal motor neuropathy,peripheral neuropathy and healthy controls in the outpatient department and inpatient department of Peking Union Medical College Hospital.They were followed up for 6 months to confirm the diagnosis.CSA measurements of the double median and ulnar nerves and cervical nerve roots and brachial plexus were performed by ultrasound.Analyze the relationship between nerve cross-sectional area and height,weight,course,muscle strength and electrophysiological parameters.Results:This study included 5 groups,a total of 204 people.The 10-point CSAs of bilateral median and ulnar nerve in the MND group were significantly different from those in the MMN and PND groups(P<0.05).The CSAs of MND-LMN group in U4(P=0.022),U5(P=0.017),U8(P=0.008)were different from healthy controls.The average CSA ratios of the proximal and distal left ulnar nerves in MND-UMN+LMN group and HC were 1.1±0.2 and 1.2±0.2,respectively(P=0.040).The average nerve cross-sectional area at each point in the MND group was related to the disease course,height and weight;the MMN group was mainly related to height;the PND group and the normal control group showed no obvious correlation with the above indicators.The average cross-sectional area of nerves in the MND group was positively correlated with the latency of motor nerve conduction.The average CSA at each point in the PND group was mainly related to the latency and conduction velocity of motor nerve conduction.There are three kinds of relationship of MMN's CB and CSA,namely CB with CSA thickening,CB without CSA thickening and CSA thickening without CB.The reproducibility test Alpha of nerve cross-sectional area by ultrasound and standardized Alpha are both 0.946.Conclusion:The nerve cross-sectional area of sonography is highly reproducible and can be used as a routine detection method for diseases such as MND,PND and MMN.The CSA of bilateral median,ulnar,cervical nerve roots and brachial plexus nerves in the MND group was significantly reduced compared with the MMN and PND groups,and the CSA ratio of the distal and proximal ulnar nerves in MND group was reduced compared with normal people.The increase in CSA in patients with MMN does not necessarily accompany motor conduction block(CB),so in order to avoid missed diagnosis,it is best to combine neuroultrasound and electrophysiological testing during diagnosis.