Differentiation Between Amyotrophic Lateral Sclerosis and Mimics Using Quantitative Analysis of Fasciculation with Muscle Ultrasound

Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis(ALS).Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020.Healthy adults from a community were recruited as healthy controls.Muscle strength was assessed using the Medical Research Council(MRC)scale.At the first visit to the hospital,patients were assessed for maximal grade of fasciculations,total fasciculation score,and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography.The sensitivity and specificity of maximal grade of fasciculations,total fasciculation score,and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses.Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9%and 9.8%,respectively(χ^(2)=172.436,P<0.01).Of the 16 limb muscles detected,the total fasciculation score[median(interquartile range)]was 29(15,41)in ALS patients and 3(0,8)in neuropathy-radiculopathy patients(Z=9.642,P<0.001).Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4,followed by patients with MRC score 5,and then in those with MRC score 0 and 1.The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6%and 93.4%,respectively(cut-off value 14).In patients with ALS,for muscles with MRC score 4 and 5,the percentage of muscles with fasciculation grades≥3 was 42.3%and 24.1%respectively,while in neuropathy-radiculopathy patients,the percentage for muscles with MRC score 4 and 5 was only 1.7%and 0,respectively.Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.

Correlations Between Serum Uric Acid Level and Disease Activity,Intrathecal Inflammation Reactivity in Patients with Multiple Sclerosis

Objective To explore the correlations between serum uric acid(UA) levels and the clinical and cerebrospinal fluid(CSF) parameters of multiple sclerosis(MS).Methods The medical reports of 47 MS patients admitted to Peking Union Medical College Hospital during 2008 and 2010 were reviewed.And 49 age-and gender-matched cerebral infarction patients were enrolled as control.The mean serum UA level of the MS patients was compared with that of the control group.The correlations between the UA levels and the clinical parameters including gender,disease duration,relapse rate,and disease disabilities as assessed by the Expanded Disability Status Scale score,were explored.Forty-one patients had CSF examinations.The correlations between the UA levels and the CSF parameters reflecting inflammation and tissue damage,including CSF protein,white blood cell count,oligoclonal band,24-hour IgG index,and myelin basic protein,were also investigated.Results The mean serum UA level in the MS patients was lower than that in the control group(247.75 ± 52.59 μmol/L vs.277.94 ± 74.33 μmol/L,P=0.025) and inversely correlated with the relapse rate(P=0.049).MS patients with lower serum UA levels tended to have higher white blood cell counts and myelin basic protein level.But there was no correlation between CSF protein levels(r=0.165,P=0.273),white blood cell counts(r=-0.051,P=0.732),IgG index(r =0.045,P=0.802),or myelin basic protein level(r =-0.248,P=0.145) and the serum UA level,respectively.Conclusion In MS patients,UA levels might partly reflect the extent of disability and inflammation.

CORRELATION BETWEEN FIBRINOGEN LEVEL AND CEREBRAL INFARCTION

Objective To investigate the correlation between plasma fibrinogen level and cerebral infarction (CI) as well as the difference of fibrinogen among subtypes of CI. Methods A case-controlled study was conducted with 131 cases of CI and 148 controls. Plasma fibrinogen levels were detected by the Clauss method. Results High fibrinogen level (3.09±0.94 g/L) was correlated with CI (OR=2.47, 95%CI: 1.51-4.04, P<0.005) at the onset stage of the disease. Persistent high fibrinogen level (3.14±0.81 g/L) at 6-month after stroke onset was detected and correlated with CI(OR=4.34,95% CI:1.80-10.51, P=0.001). Higher fibrinogen level was correlated with total anterior circulation infarction (TACI), partial anterior circulation infarction (PACI), and posterior circulation infarction (POCI) (OR=4.008, P<0.001). Higher fibrinogen level was correlated with extracranial atherosclerosis (OR=3.220, P<0.05), but not with intracranial atherosclerosis.Conclusion Fibrinogen level may be a risk factor of CI and probably correlates with subtypes of CI and distributions of atherosclerosis.

Autoimmune Encephalitis： An Expanding Frontier of Neuroimmunology

INTRODUCTIONDiscovery of the spectrum ofautoimmune encephalitis （ALE） is among the most attractive events of neurology in the past decade. AIE includes a heterogeneous group of encephalitic syndromes, which generally include two major categories： classic paraneoplastic limbic encephalitis （LE） associated with the so-called well-characterized onconeural autoantibodies against intracellular neuronal antigens （e.g., Hu, Ma2, etc.） and new-type AIE associated with autoantibodies to the neuronal surface or synaptic antigens.

Limbic Encephalitis Associated with Anti-y-aminobutyric Acid B Receptor Antibodies： A Case Series from China

Background： Autoimmune encephalitis associated with antibodies against γ-aminobutyric acid B receptor （GABABR） in patients with limbic encephalitis （LE） was first described in 2010. We present a series of klan Chinese patients tbr further clinical refinement. Methods： Serum and cerebrospinal fluid （CSF） samples from patients referred to the program of encephalitis and paraneoplastic syndrome of Peking Union Medical College Hospital were tested with indirect immunofluorescence. Clinical information of patients with anti-GABABR antibody positivity was retrospectively reviewed, and descriptive statistical analysis was performed. Results： All eighteen anti-GABABR antibody-positive cases had limbic syndromes, and electroencephalogram （EEG） or neuroimaging evidence fulfilled the diagnostic criteria of LE. Four patients had additional antibodies against Hu in serum and one had anti-N-methyl-d-aspartate receptor antibody in both sera and CSF. Seventeen （17/18） patients presented with new-onset refractory seizure or status epileptics. Twelve （12/18） patients had memory deficits, 11 （11/18） patients had personality change, 7 （7/18） patients had disturbance of consciousness, and 3 （3/18） patients showed cerebellar dysfunction. One patient with LE had progressive motor and sensory polyneuropathy. Lung cancer was detected in 6 （6/18） patients. Ten （10/18） patients showed abnormality in bilateral or unilateral mediotemporal region on magnetic resonance imaging. Ten （10/18） patients had temporal lobe epileptic activity with or without general slowing on EEG. Seventeen patients received immunotherapy and 15 of them showed neurological improvement. Four patients with lung cancer died within 1-12 months due to neoplastic complications. Conclusions： Our study demonstrates that most Han Chinese patients with anti-GABABR antibody-associated LE have prominent refractory epilepsy and show neurological improvement on immunotherapy. Patients with underlying lung tumor have a relatively poor prognosis. Testing for anti-GABABR antibodies is necessary for patients with possible LE or new-onset epilepsy with unknown etiology.

Association between large artery stenosis,cerebral small vessel disease and risk of ischemic stroke

We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospective population-based Shunyi Study,1,082 stroke-free participants aged 55.9±9.1 years were included.Participants were followed for incident stroke throughout the study period(2013-2019).Total small vessel disease score was used to measure CSVD burden.Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound.We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models.During a mean follow-up of 4.2 years,34 participants(3.1%)experienced at least one ischemic stroke.Severe LAS(≥50% stenosis versus no stenosis:HR=3.27(95%CI:1.31-8.18))and high CSVD burden(total small vessel disease score 2-4 versus 0 point:HR=12.73(4.83-33.53))were associated with increased stroke risk independently.In multivariate models,CSVD burden(7.72%)explained a larger portion of the variation in stroke risk than severity of LAS(3.49%).Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects,while those with high CSVD burden deserve more attention in primary prevention of stroke.

Inflammatory biomarkers and cerebral small vessel disease:a community-based cohort study

Background and purpose Although inflammation has been proposed to be a candidate risk factor for cerebral small vessel disease(CSVD),previous findings remain largely inconclusive and vary according to disease status and study designs.The present study aimed to investigate possible associations between inflammatory biomarkers and MRI markers of CSVD.Methods A group of 15 serum inflammatory biomarkers representing a variety of those putatively involved in the inflammatory cascade was grouped and assessed in a cross-sectional study involving 960 stroke-free subjects.The biomarker panel was grouped as follows:systemic inflammation(high-sensitivity C reactive protein(hsCRP),interleukin 6 and tumour necrosis factorα),endothelial-related inflammation(E-selectin,P-selectin,intercellular adhesion molecule 1,vascular cell adhesion molecule 1(VCAM-1),CD40 ligand,lipoprotein-associated phospholipase A2,chitinase-3-like 1 protein and total homocysteine(tHCY))and media-related inflammation(matrix metalloproteinases 2,3 and 9,and osteopontin).The association(s)between different inflammatory groups and white matter hyperintensity(WMH),lacunes,cerebral microbleeds(CMBs),enlarged perivascular space(PVS)and the number of deep medullary veins(DMVs)were investigated.Results High levels of serum endothelial-related inflammatory biomarkers were associated with both increased WMH volume(R^(2)=0.435,p=0.015)and the presence of lacunes(R^(2)=0.254,p=0.027).Backward stepwise elimination of individual inflammatory biomarkers for endothelial-related biomarkers revealed that VCAM-1 was significant for WMH(β=0.063,p=0.005)and tHCY was significant for lacunes(β=0.069,p<0.001).There was no association between any group of inflammatory biomarkers and CMBs or PVS.Systemic inflammatory biomarkers were associated with fewer DMVs(R^(2)=0.032,p=0.006),and backward stepwise elimination of individual systemic-related inflammatory biomarkers revealed that hsCRP(β=−0.162,p=0.007)was significant.Conclusion WMH and lacunes were associated with endothelial-related inflammatory biomarkers,and fewer DMVs were associated with systemic inflammation,thus suggesting different underlying inflammatory processes and mechanisms.

Study on variation trend of repetitive nerve stimulation waveform in amyotrophic lateral sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower neurons with no effective cure. Electrophysiological studies have found decremental responses during low-frequency repetitive nerve stimulation (RNS) except for diffused neurogenic activities. However, the difference between ALS and generalized myasthenia gravis (GMG) in terms of waveform features is unclear. In the current study, we explored the variation trend of the amplitudes curve between ALS and GMG with low-frequency, positive RNS, and the possible mechanism is discussed preliminarily. Methods: A total of 85 ALS patients and 41 GMG patients were recruited. All patients were from Peking Union Medical College Hospital (PUMCH) between July 1,2012 and February 28,2015. RNS study included ulnar nerve, accessory nerve and facial nerve at 3 Hz and 5 Hz stimulation. The percentage reduction in the amplitude of the fourth or fifth wave from the first wave was calculated and compared with the normal values of our hospital. A 15% decrease in amplitude is defined as a decrease in amplitude. Results: The decremental response at low-frequency RNS showed the abnormal rate of RNS decline was 54.1%(46/85) in the ALS group, and the results of different nerves were 54.1 %(46/85) of the accessory nerve, 8.2%(7/85) of the ulnar nerve and 0%(0/85) of the facial nerve stimulation, respectively. In the GMG group, the abnormal rate of RNS decline was 100%(41/41) at low-frequency RNS of accessory nerves. However, there was a significant difference between the 2 groups in the amplitude after the sixth wave. Conclusions: Both groups of patients are able to show a decreasing amplitude of low-frequency stimulation RNS, but the recovery trend after the sixth wave has significant variation. It implies the different pathogenesis of NMJ dysfunction of these 2 diseases.

Utility and Safety of Intrathecal Methotrexate Treatment in Severe Anti-N-methyI-D-aspartate Receptor Encephalitis： A Pilot Study

Background： Anti-N-methyl-D-aspartate receptor （anti-NMDAR） encephalitis is a treatable autoimmune neurologic syndrome that occurs with or without tumor association. However, some severe cases are refractory to systemic immunotherapy. This pilot study aimed to evaluate the utility and safety of intrathecal methotrexate injection for severe patients with anti-NMDAR encephalitis who did not respond to first-line immunotherapy. Methods： Intrathecal injections with methotrexate and dexamethasone were performed weekly in four legible patients within consecutive 4 weeks. Cerebrospinal fluid （CSF） was collected at baseline and each time of intrathecal injection lbr identification of anti-NMDAR antibody titers. Results： Significant clinical improvement was observed in three patients associated with a stepwise decrease of CSF anti-NMDAR antibody titers （maximum： 1/320 to minimum： 1/10）. After 2 months of follow-up, they were able to follow simple commands and had appropriate interactions with people （modified Rankin scale [mRS] of 0-2）. At 12 months of follow-up, they all had returned to most activities of daily life （.mRS of 0）, and no relapses were reported. One patient showed no clinical improvement and died of neurologic complications. Conclusions： lntrathecal treatment may be a potentially useful supplementary therapy in severely affected patients with anti-NMDAR encephalitis. Further large cohort study and animal experiment may help us elaborate the utility of intrathecal injection of methotrexate and its mechanism of action.

Monitoring Value of Multimodal Magnetic Resonance Imaging in Disease Progression of Amyotrophic Lateral Sclerosis: A Prospective Observational Study

Background: Ongoing efforts have been made to identify new neuroimaging markers to track amyotrophic lateral sclerosis (ALS) progression. This study aimed to explore the monitoring value of multimodal magnetic resonance imaging (MRI) in the disease progression of ALS. Methods: From September 2015 to March 2017, ten patients diagnosed with ALS in Peking Union Medical College Hospital completed head MRI scans at baseline and during follow-up. Multimodal MRI analyses, including gray matter (GM) volume measured by voxel-based morphometry;cerebral blood flow (CBF) evaluated by arterial spin labeling;functional connectivity, including low-frequency fluctuation (fALFF) and regional homogeneity (ReHo), measured by resting-state functional MRI;and integrity of white-matter (WM) fiber tracts evaluated by diffusion tensor imaging, were performed in these patients. Comparisons of imaging metrics were made between baseline and follow-up using paired t-test. Results: In the longitudinal comparisons, the brain structure (GM volume of the right precentral gyri, left postcentral gyri, and right thalami) and perfusion (CBF of the bilateral temporal poles, left precentral gyri, postcentral gyri, and right middle temporal gyri) in both motor and extramotor areas at follow-up were impaired to different extents when compared with those at baseline (all P < 0.05, false discovery rate adjusted). Functional connectivity was increased in the motor areas (fALFF of the right precentral gyri and superior frontal gyri, and ReHo of right precentral gyri) and decreased in the extramotor areas (fALFF of the bilateral middle frontal gyri and ReHo of the right precuneus and cingulate gyri) (all P < 0.001, unadjusted). No significant changes were detected in terms of brain WM measures. Conclusion: Multimodal MRI could be used to monitor short-term brain changes in ALS patients.

The Discrepancy of Neurological Diseases between China and Western Countries in Recent Two Decades

INTRODUCTION Neurological diseases are characterized by high frequency of disability and mortality with pathogenesis largely unknown. Genetic, refractory, and rare diseases account tbr a large proportion of neurological diseases： sympathetically, limited curable treatments are available. Hundreds of millions of people worldwide are affected by neurological disorders. The diagnosis and treatment of neurological disorders have made significant progress in recent years, especially in the past two decades with the rapid development of technology.

Single-fiber Electromyography in the Extensor Digitorum Communis for the Predictive Prognosis of Ocular Myasthenia Gravis： A Retrospective Study of 102 Cases

Background： Single-fiber electromyography （SFEMG） abnormality in the extensor digitorum communis （EDC） was reported in ocular myasthenia gravis （OMG）, which indicated subclinical involvement beyond extraocular muscles in OMG patients. The relationship between the abnormal findings of SFEMG in EDC and the probability for OMG to develop generalized myasthenia gravis （GMG） is unknown, This retrospective study aimed to determine the predictive value of abnormality of SFEMG in EDC of OMG patients. Methods： One-hundred and two OMG patients underwent standard clinical diagnosis process and SFEMG test in EDC muscle when diagnosed and were clinically followed up for 5 years. The SFEMG data were compared between different clinical groups according to thymus status, onset age, and different outcome of OMG developing. Chances of progressing to GMG were compared between two different groups according to SFEMG and repetitive nerve stimulation （RNS） results, acetylcholine receptor antibody （AchRAb） titer, thymus status, and onset age. Results： Abnormal SFEMG results were observed in 84 （82.4%） patients. The mean jitter, percentage of jitter 〉55 Its （%）, and blocking were higher in OMG patients than in healthy volunteers. There were no statistical differences in jitter analysis between thymoma group and non-thymoma group （P = 0.65）, or between the later OMG group and the later GMG group （P = 0.31）, including mean jitter, percentage of jitter 〉55 Its （%）, and blocking. Elderly group （〉45 years old） had a higher mean jitter than younger group （t = 2.235, P = 0.028）. Total 55 OMG developed GMG, including 47 in abnormal SFEMG group while 8 in normal SFEMG group. There was no statistical difference in the conversion rates between the two groups （x^2 = 0.790, P = 0.140）. RNS abnormality, AchRab titer, or onset age had no correlation with OMG prognosis （P = 0.150, 0.070, 0.120, respectively） while thymoma did （x^2 = 0.510, P = 0.020）. Conclusion： SFEMG test in the EDC showed high abnormality in OMG, suggesting subclinical involvement other than extraocular muscles. Nevertheless, the abnormal jitter analysis did not predict the prognosis of OMG according to clinical follow-up.

Pattern Differences of Small Hand Muscle Atrophy in Amyotrophic Lateral Sclerosis and Mimic Disorders

Background： Amyotrophic lateral sclerosis （ALS） and some mimic disorders, such as distal-type cervical spondylotic amyotrophy （LISA）, Hirayama disease （HD）, and spinobulbar muscular atrophy （SBMA） may present with intrinsic hand muscle atrophy. This study aimed to investigate different patterns of small hand muscle involvement in ALS and some mimic disorders. Methods： We compared the abductor digiti minimi/abductor pollicis brevis （ADM/APB） compound muscle action potential （（＇MAP） ratios between 200 ALS patients, 95 patients with distal-type CSA, 88 HD patients, 43 SBMA patients, and 150 normal controls. Results： The ADM/APB （？MAP amplitude ratio was significantly higher in the ALS patients （P 〈 0.001） than that in the normal controls. The ADM/APB CMAP amplitude ratio was significantly reduced in the patients with distal-type CSA （P 〈 0,001 ） and the H I） patients （P 〈 0.001 ） compared with that in the normal controls. The patients with distal-type CSA had significantly lower APB CMAP amplitude than the HD patients （P- 0.004）. The ADM/APB CMAP amplitude ratio was significantly lower in the HD patients （P 〈 0.001 ） than that in the patients with distal-type CSA. The ADM/APB CMAP amplitude ratio of the SBMA patients was similar to that of the normal controls （P = 0.862）. An absent APB CMAP and an abnormally high ADM/APB CMAP amplitude ratio （_〉4.5） were observed exclusively in the ALS patients. Conclusions： The different patterns of small hand muscle atrophy between the ALS patients and the patients with mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders.

Metabolic syndrome, intracranial arterial stenosis and cerebral small vessel disease in community- dwelling populations

Background and purpose This study aimed to investigate the association of metabolic syndrome(MetS)with both intracranial atherosclerotic stenosis(ICAS)and imaging markers of cerebral small vessel disease(CSVD)in a community-based sample.Methods This study included 943 participants(aged 55.6±9.2 years,36.1%male)from the community-based Shunyi cohort study.MetS was defined according to the joint interim criteria and quantified by the MetS severity Z-score.ICAS was evaluated by brain magnetic resonance angiography.The MRI markers of CSVD,including white matter hyperintensities(WMHs),lacunes,cerebral microbleeds(CMBs)and enlarged perivascular spaces(EPVS),were assessed.Multiple regression models were used to investigate the association of MetS severity Z-score with ICAS and these CSVD markers.Results We found that risk of ICAS(OR=1.75,95%CI 1.39 to 2.21,p<0.001)increased consistently with MetS severity.MetS severity was significantly associated with higher risks of WMH volume(β=0.11,95%CI 0.01 to 0.20,p=0.02)and lacunes(OR=1.28,95%CI 1.03 to 1.59,p=0.03)but not the presence of CMBs(OR=0.93,95%CI 0.74 to 1.16,p=0.51)and PVS severity(EPVS in basal ganglia:OR=0.96,95%CI 0.84 to 1.09,p=0.51 and EPVS in white matter:OR=1.09,95%CI 0.96 to 1.23,p=0.21).Conclusions Our findings suggest that WMH and lacunes share risk factors with atherosclerosis of the cerebral artery,whereas the impact of glucose and lipid metabolic disorder to CMB or EPVS might be weak.

Agraphia in Amyotrophic Lateral Sclerosis with Frontotemporal Lobe Degeneration

Frontotemporal lobe degeneration （FTLD） refers to a neurodegenerative dementia syndrome, which could be clinically classified into behavioral and language variant. Amyotrophic lateral sclerosis （ALS） is a progressive neurological disorder involving both upper motor neuron （UMN） and lower motor neuron （LMN）, eventually leading to muscle atrophy and weakness, bulbar palsy, and respiratory failure.

Quantitating Changes in Jitter and Spike Number Using Concentric Needle Electrodes in Amyotrophic Lateral Sclerosis Patients

Background： Single-fiber electromyography （SFEMG） has been suggested as a quantitative method for supporting chronic partial denervation in amyotrophic lateral sclerosis （ALS） by the revised El Escorial criteria. Although concentric needle （CN） electrodes have been used to assess jitter in myasthenia gravis patients and healthy controls, there are few reports using CN electrodes to assess motor unit instability and denervation in neurogenic diseases. The aim of this study was to determine whether quantitative changes in jitter and spike number using CN electrodes could be used for ALS studies. Methods： Twenty-seven healthy controls and 23 ALS patients were studied using both CN and single-fiber needle （SFN） electrodes on the extensor digitorum communis muscle with an SFEMG program. The SFN-jitter and SFN-fiber density data were measured using SFN electrodes. The CN-jitter and spike number were measured using CN electrodes. Results： The mean CN-j itter was significantly increased in ALS patients （47.3 ±17.0 μs） than in healthy controls （27.4 ± 3.3 las） （P 〈 0.001 ）. Besides, the mean spike number was significantly increased in ALS patients （2.5 ± 0.5） than in healthy controls （1.7 ± 0.3） （P 〈 0.001）. The sensitivity and specificity in the diagnosis of ALS were 82.6% and 92.6% for CN-jitter （cut-offvalue： 32 gs）, and 91.3% and 96.3% for the spike number （cut-off value： 2.0）, respectively. There was no significant difference between the SFN-jitter and CN-jitter in ALS patients; meanwhile, there was no significant difference between the SFN-jitter and CN-jitter in healthy controls. Conclusion： CN-jitter and spike number could be used to quantitatively evaluate changes due to denervation-reinnervation in ALS.

Impact of regional differences in stroke symptom awareness and low-income status on seeking emergency medical service in China

Background:Unawareness of stroke symptoms and low income are two barriers that affect the seeking of emergency medical service(EMS).This study aimed to assess the effect of unawareness and low income on seeking EMS and to investigate the regional distribution of the unawareness and low-income status and their associations with failing to call EMS in China.Methods:A total of 187,723 samples from the China National Stroke Screening Survey was interviewed cross-sectionally.Four status of awareness and annual income were identified:unaware and low-income,unaware-only,low-income-only,and aware and regular income.The outcomes were whether they intended to call EMS or not.The regional distribution of each status and their associations with not calling EMS were presented.Results:The status of unaware and low-income,unaware-only,and low-income-only accounted for 6.3%(11,806/187,673),11.9%(22,241/187,673),and 21.5%(40,289/187,673)of the total sample,respectively.Not calling EMS was significantly associated with the status of unaware and low-income(odds ratio[OR]:3.21,95%confidence interval[Cl]:3.07-3.35),unaware-only(OR:2.38,95%Cl:2.31-2.46),and low-income-only(OR:1.67,95%Cl:1.63-1.71),compared with the aware and regular income status.The Midwest regions had higher percentages of people in the unaware and low-income status;the East,South,and Central had higher percentages of unaware-only status;the North and Northeast regions had a higher percentage of low-income-only status,compared with other regions.Conclusion:The existence of the regional difference in unawareness and low income justifies the specific stroke education strategies for the targeted regions and population.

A report on paraneoplastic motor neuron disease

To the Editor: Motor neuron disease (MND) is marked by upper (UMN) or lower (LMN) motor neuron signs and symptoms,[1] which in various combinations form the basis for MND classification. In this regard, amyotrophic lateral sclerosis (ALS) is the most common subtype.[2] Although otherwise deemed an untreatable degenerative disease, there is now increasing evidence of more heterogeneous pathogenesis, signaling a link between MND and paraneoplastic syndromes.[3].

D-cycloserin,a NMDA-agonist may be a treatment option for anti-NMDAR encephalitis

Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis is caused by reversible neuron dysfunction associated an autoantibody-mediated decrease of NMDAR in the entire brain.A N-methyl-D-aspartate(NMDA)-agonist treatment for anti-NMDAR encephalitis might have a role considering its specific mechanism.The authors used D-cycloserine,a partial NMDA-agonist in a refractory case with prolonged intensive care unit duration.A 13-year-old female presented with headache,cognitive deterioration,generalized seizures,coma and hypoventilation with required mechanical ventilation.Anti-NMDAR antibodies were identified in cerebrospinal fluid and serum confirming anti-NMDAR encephalitis.The patient was refractory to first-line and second-line immunotherapy and removal of ovary teratoma.D-cycloserine was then administered and her symptoms improved gradually and significantly.This is the first reported case in which D-cycloserine was applied to this disease.D-cycloserine might be a potential option as specific treatment in anti-NMDAR encephalitis.

Eiehavioral Symptoms in Motor Neuron Disease and Their Negative Impact on Caregiver Burden

Background： The spectrum of abnormal behaviors in amyotrophic lateral sclerosis/motor neuron disease （ALS/MND） has been described, but its practical meaning, namely its impact on caregiver burden, has not been clearly documented in Chinese population. This study aimed to assess the distribution of abnormal behaviors in Chinese population, and to analyze the relationship between behavior changes and caregivcr burden. Methods： Sixty-five patients with ALS/MND have been consecutively enrolled into registry platform of Peking Union Medical College Hospital. An investigation was performed to these patients and their caregivers using the revised ALS function rating scale, Frontal Behavioral Inventory-ALS version, the Frontal Assessment Battery, and the Caregiver Burden Inventory. Results： Twenty-eight （43.1%） patients displayed abnormal behaviors of varying degrees, with one fulfilling the diagnostic criteria of frontotemporal lobe degeneration. Irritability, logopenia, and inflexibility ranked top 3 of abnormal behavior list. Correlation analysis revealed that the degree of behavioral change and frontal cognitive status were significantly associated with caregiver burden, with more extensive impact from disinhibitive behaviors. Analysis of covariance analysis showed that after associated factors were corrected, caregivers of patients with moderate to severe behavior change reported significantly heavier developmental burden, physical burden, and total burden than those with no behavioral change. Conclusions： Nettrobehavioral symptoms could present in around 40% of Chinese patients with ALS/MND, and the distribution of these behaviors was also unique. Besides, abnormal behaviors were highly related to caregivers＇ burden.