Impact of regional differences in stroke symptom awareness and low-income status on seeking emergency medical service in China / 中华医学杂志(英文版)

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 [CI]: 3.07-3.35), unaware-only (OR: 2.38, 95% CI: 2.31-2.46), and low-income-only (OR: 1.67, 95% CI: 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.

HTRA1-related autosomal dominant cerebral small vessel disease / 中华医学杂志(英文版)

BACKGROUND@#Homozygous or compound heterozygous mutations in high temperature requirement serine peptidase A1 (HTRA1) gene are responsible for cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Recently, increasing evidence has shown that heterozygous HTRA1 mutations are also associated with cerebral small vessel disease (CSVD) with an autosomal dominant pattern of inheritance. This study was aimed to analyze the genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD.@*METHODS@#We presented three new Chinese cases of familial CSVD with heterozygous HTRA1 mutations and reviewed all clinical case reports and articles on HTRA1-related autosomal dominant CSVD included in PUBMED by the end of March 1, 2020. CARASIL probands with genetic diagnosis reported to date were also reviewed. The genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD were summarized and analyzed by comparing with CARASIL.@*RESULTS@#Forty-four HTRA1-related autosomal dominant CSVD probands and 22 CARASIL probands were included. Compared with typical CARASIL, HTRA1-related autosomal dominant probands has a higher proportion of vascular risk factors (P < 0.001), a later onset age (P < 0.001), and a relatively slower clinical progression. Alopecia and spondylosis can be observed, but less than those in the typical CARASIL. Thirty-five heterozygous mutations in HTRA1 were reported, most of which were missense mutations. Amino acids located close to amino acids 250-300 were most frequently affected, followed by these located near 150∼200. While amino acids 250∼300 were also the most frequently affected region in CARASIL patients, fewer mutations precede the 200th amino acids were detected, especially in the Kazal-type serine protease domain.@*CONCLUSIONS@#HTRA1-related autosomal dominant CSVD is present as a mild phenotype of CARASIL. The trend of regional concentration of mutation sites may be related to the concentration of key sites in these regions which are responsible for pathogenesis of HTRA1-related autosomal dominant CSVD.

Study on variation trend of repetitive nerve stimulation waveform in amyotrophic lateral sclerosis / 中华医学杂志(英文版)

BACKGROUND@#Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor 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.

Clinical Characteristics of Autoimmune Disease with Dual Seropositive Antibodies of Leucine-rich Glioma Inactivated 1 and Contactin-associated Protein 2 / 中国医学科学院学报

Objective To explore the clinical characteristics of autoimmune disease with dual seropositive antibodies of leucine-rich glioma inactivated 1(LGI1)and contactin-associated protein 2(Caspr2).Methods The clinical data of seven patients with dual seropositive LGI1 and Caspr2 antibodies who were admitted to the Neurology Department of Peking Union Medical College Hospital from July 2014 to December 2017 were retrospectively analyzed.Results Central,peripheral and autonomic nervous systems were all involved in the seven cases;100%(7/7)presented with insomnia,myokymia,neuropahic pain and hyperhydrosis;71%(5/7)showed memory decline or psychiatric and behavioral symptoms;57%(4/7)had urinary hesitation or constipation;and 43%(3/7)had seizure.Electromyography showed 100%(6/6) of the patients had prolonged afterdischarges following normal M waves and/or abnormal spontaneous firing.Electroencephalography revealed slow waves or basic rhythm slowing in 71%(5/7)of patients.Electrocardiography showed sinus tachycardia,axis deviation,and prolonged QT intervals in 71%(5/7)of patients.One patient died from arrhythmia before immunotherapy.One died from pulmonary infection after immunotherapy.Improvement with immunotherapy was documented in the other five cases.No relapse was noted during the 1-2-year follow-up.Conclusions Autoimmune disease with dual seropositive antibodies of LGI1 and Caspr2 can diffusely affect the central,peripheral,and autonomic nervous systems.The possibility of this disease should be considered in patients with acute and subacute onset of neuropsychiatric symptoms,especially in patients with accompanying insomnia,myokymia,and hyperhydrosis.

Monitoring Value of Multimodal Magnetic Resonance Imaging in Disease Progression of Amyotrophic Lateral Sclerosis: A Prospective Observational Study / 中华医学杂志(英文版)

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.

Utility and Safety of Intrathecal Methotrexate Treatment in Severe Anti-N-methyl-D-aspartate Receptor Encephalitis: A Pilot Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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 for identification of anti-NMDAR antibody titers.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>Intrathecal 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.</p>

Prevalence and Risk Factors of Cerebral Small Vessel Disease in a Chinese Population-Based Sample / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Epidemiological data of cerebral small vessel disease (CSVD) in the general population of China are lacking. We report on the prevalence of lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMBs) in a community-based sample in China and compare the results with those of other studies. METHODS: This was a cross-sectional analysis of the population-based Shunyi Study in China. A total of 1,211 stroke-free participants (mean age, 55.6±9.3 years; 37.4% men) with available 3 Tesla (3T) magnetic resonance images were included in this analysis. Demographic information and risk factor data were assessed. The overall and age-specific prevalence of lacunes, WMH, and CMBs was evaluated. Associations between cardiovascular risk factors and the presence of these lesions were analyzed by multiple logistic regression. RESULTS: Our study showed a prevalence of 14.5% for lacunes, 72.1% for periventricular hyperintensity (PVH), 65.4% for deep white matter hyperintensity (DWMH), and 10.6% for CMBs. When compared with other community-based samples, individuals in the same age group showed a higher burden of lacunes and a relatively lower prevalence of CMBs. Advanced age was independently associated with the prevalence of these CSVD markers, while the presence of hypertension increased the risk of lacunes, PVH/DWMH, and CMBs in deep or infratentorial locations. CONCLUSIONS: A higher burden of lacunes but a relatively lower prevalence of CMBs was observed in this Chinese population. This notable result highlights the challenge of CSVD prevention in China. Chinese have a risk factor profile for CSVD similar to those in other populations.

A Novel AGRN Mutation Leads to Congenital Myasthenic Syndrome Only Affecting Limb-girdle Muscle / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Congenital myasthenic syndromes (CMSs) are a group of clinically and genetically heterogeneous disorders caused by impaired neuromuscular transmission. The defect of AGRN was one of the causes of CMS through influencing the development and maintenance of neuromuscular transmission. However, CMS reports about this gene mutation were rare. Here, we report a novel homozygous missense mutation (c.5302G>C) of AGRN in a Chinese CMS pedigree.</p><p><b>METHODS</b>We performed a detailed clinical assessment of a Chinese family with three affected members. We screened for pathogenic mutations using a disease-related gene panel containing 519 genes associated with genetic myopathy (including 17 CMS genes).</p><p><b>RESULTS</b>In the family, the proband showed limb-girdle pattern of weakness with sparing of ocular, facial, bulbar, and respiratory muscles. Repetitive nerve stimulation showed a clear decrement of the compound muscle action potentials at 3 Hz only. Pathological analysis of the left tibialis anterior muscle showed predominance of type I fiber and the presence of scattered small angular fibers. The proband's two elder sisters shared a similar but more severe phenotype. By gene analysis, the same novel homozygous mutation (c.5302G>C, p. A1768P) of AGRN was identified in all three affected members, whereas the same heterozygous mutation was found in both parents, revealing an autosomal recessive transmission pattern. All patients showed beneficial responses to adrenergic agonists.</p><p><b>CONCLUSIONS</b>This study reports a Chinese pedigree in which all three children carried the same novel AGRN mutation have CMS only affecting limb-girdle muscle. These findings might expand the spectrum of mutation in AGRN and enrich the phenotype of CMS.</p>

Quantitating Changes in Jitter and Spike Number Using Concentric Needle Electrodes in Amyotrophic Lateral Sclerosis Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Single-fiber electromyography (SFEMG) has been suggested as a quantitative method for supporting chronic partial denervation in amyotrophic lateral sclerosis (ALS) by the revised EI 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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>The mean CN-jitter was significantly increased in ALS patients (47.3 ± 17.0 μs) than in healthy controls (27.4 ± 3.3 μs) (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-off value: 32 μs), 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.</p><p><b>CONCLUSION</b>CN-jitter and spike number could be used to quantitatively evaluate changes due to denervation-reinnervation in ALS.</p>

Pattern Differences of Small Hand Muscle Atrophy in Amyotrophic Lateral Sclerosis and Mimic Disorders / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Amyotrophic lateral sclerosis (ALS) and some mimic disorders, such as distal-type cervical spondylotic amyotrophy (CSA), 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.</p><p><b>METHODS</b>We compared the abductor digiti minimi/abductor pollicis brevis (ADM/APB) compound muscle action potential (CMAP) ratios between 200 ALS patients, 95 patients with distal-type CSA, 88 HD patients, 43 SBMA patients, and 150 normal controls.</p><p><b>RESULTS</b>The ADM/APB CMAP 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 HD 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.</p><p><b>CONCLUSIONS</b>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.</p>

Importance of sample size for the estimation of repeater F waves in amyotrophic lateral sclerosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In amyotrophic lateral sclerosis (ALS), repeater F waves are increased. Accurate assessment of repeater F waves requires an adequate sample size.</p><p><b>METHODS</b>We studied the F waves of left ulnar nerves in ALS patients. Based on the presence or absence of pyramidal signs in the left upper limb, the ALS patients were divided into two groups: One group with pyramidal signs designated as P group and the other without pyramidal signs designated as NP group. The Index repeating neurons (RN) and Index repeater F waves (Freps) were compared among the P, NP and control groups following 20 and 100 stimuli respectively. For each group, the Index RN and Index Freps obtained from 20 and 100 stimuli were compared.</p><p><b>RESULTS</b>In the P group, the Index RN (P = 0.004) and Index Freps (P = 0.001) obtained from 100 stimuli were significantly higher than from 20 stimuli. For F waves obtained from 20 stimuli, no significant differences were identified between the P and NP groups for Index RN (P = 0.052) and Index Freps (P = 0.079); The Index RN (P < 0.001) and Index Freps (P < 0.001) of the P group were significantly higher than the control group; The Index RN (P = 0.002) of the NP group was significantly higher than the control group. For F waves obtained from 100 stimuli, the Index RN (P < 0.001) and Index Freps (P < 0.001) of the P group were significantly higher than the NP group; The Index RN (P < 0.001) and Index Freps (P < 0.001) of the P and NP groups were significantly higher than the control group.</p><p><b>CONCLUSIONS</b>Increased repeater F waves reflect increased excitability of motor neuron pool and indicate upper motor neuron dysfunction in ALS. For an accurate evaluation of repeater F waves in ALS patients especially those with moderate to severe muscle atrophy, 100 stimuli would be required.</p>

Single-fiber Electromyography in the Extensor Digitorum Communis for the Predictive Prognosis of Ocular Myasthenia Gravis: A Retrospective Study of 102 Cases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>Abnormal SFEMG results were observed in 84 (82.4%) patients. The mean jitter, percentage of jitter >55 μs (%), 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 μs (%), 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 (χ2 = 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 (χ2 = 0.510, P = 0.020).</p><p><b>CONCLUSION</b>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.</p>

Behavioral Symptoms in Motor Neuron Disease and Their Negative Impact on Caregiver Burden / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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 caregiver burden.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>Neurobehavioral 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.</p>

Diagnosis of Muscular Dystrophy Using Western Blot with Micro-sample of Muscle / 中国医学科学院学报

<p><b>OBJECTIVE</b>To diagnose muscular dystrophy using Western blot (WB) by improving the method of the protein extraction.</p><p><b>METHOD</b>Firstly,we compared the effect of different sample buffer solutions and processing Methods on the extraction of muscle protein in rats,then selected the appropriate extracting method and the process of the muscular protein.</p><p><b>RESULTS</b>We put the selected sample buffer into the micro-sample,then mixed. The concentration of the extracting protein was much more,and the loss during the process was much less. We extracted enough protein in 62 cases. The protein bands were showed clearly by WB,and the abnormal protein bands were shown in some patients. Compared with the Results of immunohistochemical staining detected the severe abnormal expressions of Dys-R,Dys-C,and Dys-N in the specimens,we did not detect the corresponding target band in WB. We detected the target protein band of the specimens were abnormal position,light or normal staining in WB,while Dys were mildly expressed in immunohistochemical staining.</p><p><b>CONCLUSIONS</b>The improved protein extraction method can save the muscle tissue,and the protein bands can be used for diagnosing the muscular dystrophy. For clinically suspected patients with dystrophinopathy,if normal or mild deficiency is shown by immunohistochemistry,WB should be applied to detect the dystrophin protein band.</p>

Treatment of Mild-to-moderate Bronchial Asthma (Heat Wheezing Syndrome) Patients at Acute Onset with Western Medicine Combined Danlong Oral Liquid: a Multi-center, Randomized Double- blinded, Positive-controlled Clinical Trial / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the efficacy and safety of Danlong Oral Liquid (DOL) combined Western medicine (WM) in treating mild-to-moderate bronchial asthma patients (heat wheezing syndrome) at acute onset.</p><p><b>METHODS</b>Totally 480 mild-to-moderate bronchial asthma patients (heat wheezing syndrome) at acute onset were randomly assigned to two groups in the ratio 3:1, the treatment group (360 cases) and the control group (120 cases). All patients received basic WM treatment. Patients in the treatment group took DOL, 10 mL each time, 3 times per day for 7 days in total, while those in the control group took Kechuanning Oral Liquid (KOL) , 10 mL each time, 3 times per day for 7 days in total. Efficacy for asthma symptoms, lung functions and scores of TCM syndrome and/or main symptoms were evaluated.</p><p><b>RESULTS</b>The percentage of clinical control and significant effectiveness of asthma symptoms in the treatment group was significantly higher than that of the control group (77.36% vs 56.07%, P < 0.01). The percentage of clinical control and significant effectiveness of lung functions in the treatment group was significantly higher than that of the control group (74.28% vs 50.00%, P < 0.01). The anterior-posterior difference in scores of TCM syndrome was significantly superior in the treatment group than in the control group (-11.26 ± 4.70 vs -9.21 ± 5.09, P < 0.01). The anterior-posterior difference in scores of main symptoms was significantly better in the treatment group than in the control group (-6.58 ± 3.08 vs -5.16 ± 3.45, P < 0.01). The incidence of adverse reactions was significantly lower in the treatment group than in the control group [1.73% (6/346 cases) vs 10.17% (12/118 cases) , P < 0.05].</p><p><b>CONCLUSION</b>DOL combined WM was superior to KOL in treating mild-to-moderate bronchial asthma patients (heat wheezing syndrome) at acute onset.</p>

F Wave Study in Amyotrophic Lateral Sclerosis: Assessment of Segmental Motoneuronal Dysfunction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Dysfunctional spinal circuit may play a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). The purpose of this study was to use F waves for assessment of segmental motoneuronal excitability following upper motor neuron (UMN) dysfunctions in ALS.</p><p><b>METHODS</b>We studied the F waves of 152 ulnar nerves recorded from abductor digiti minimi in 82 patients with ALS. Two groups of hands were defined based on the presence or absence of pyramidal signs in the same upper limb. The group with pyramidal signs in the upper limbs was designated as the P group, and the group without pyramidal signs in the upper limbs was designated as the NP group.</p><p><b>RESULTS</b>The mean (P < 0.001), median (P < 0.001) and maximum (P = 0.035) F wave amplitudes, mean (P < 0.001), median (P < 0.001) and maximum (P = 0.003) F/M amplitude ratio, index repeating neuron (P < 0.001) and index repeater F waves (P < 0.001) of the P group were significantly increased compared with the NP group. No significant differences were identified for F wave chronodispersion (P = 0.628), mean F wave latency (P = 0.151), minimum F wave latency (P = 0.211), maximum F wave latency (P = 0.199), F wave persistence (P = 0.738), F wave duration (P = 0.152), F wave conduction velocity (P = 0.813) and number of giant F waves (P = 0.072) between the two groups.</p><p><b>CONCLUSIONS</b>In this study, increased F wave amplitude, F/M amplitude ratio and number of repeater F waves reflected enhanced segmental motoneuronal excitability following UMN dysfunctions in ALS.</p>

Asynchronization in Changes of Electrophysiology and Pathology of Spinal Cord Motor Neurons in Rats Following Middle Cerebral Artery Occlusion / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Motor dysfunction is common in stroke patients. Clinical electrophysiological studies suggest that transsynaptic degeneration occurred in the lower motor neurons, while pathological evidence is lacked. This study aimed to combine the electrophysiological and pathological results to prove the existence of transsynaptic degeneration in the motor system after stroke.</p><p><b>METHODS</b>Modified neurologic severity score, electrophysiological, and pathological assessments were evaluated in rats before middle cerebral artery occlusion (MCAO), and at 24 hours, 7 days, and 14 days after MCAO. Paired and independent-sample t-tests were applied to assess the changes of electrophysiological and pathological data.</p><p><b>RESULTS</b>Compound motor action potential amplitude in the paretic side was significantly lower than the nonparetic side at both 24 hours (61.9 ± 10.4 vs. 66.6 ± 8.9, P < 0.05) and 7 days (60.9 ± 8.4 vs. 67.3 ± 9.6, P < 0.05) after MCAO. Motor unit number estimation of the paretic side was significantly less than the nonparetic side (379.0 ± 84.6 vs. 445.0 ± 89.5, P < 0.05) at 7 days after MCAO. Until 14 days after stroke, the pathological loss of motor neurons was detected. Motor neurons in 14-day MCAO group were significantly decreased, compared with control group (5.3 ± 0.7 vs. 7.3 ± 1.8, P < 0.05).</p><p><b>CONCLUSIONS</b>Both electrophysiological and pathological studies showed transsynaptic degeneration after stroke. This study identified the asynchronization in changes of electrophysiology and pathology. The abnormal physiological changes and function impairment can be detected in the early stage and recovered quickly, while the pathological loss of motor neuron can be detected only in a later stage.</p>

Limbic Encephalitis Associated with Anti-γ-aminobutyric Acid B Receptor Antibodies: A Case Series from China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Autoimmune encephalitis associated with antibodies against γ-aminobutyric acid B receptor (GABA B R) in patients with limbic encephalitis (LE) was first described in 2010. We present a series of Han Chinese patients for further clinical refinement.</p><p><b>METHODS</b>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-GABA B R antibody positivity was retrospectively reviewed, and descriptive statistical analysis was performed.</p><p><b>RESULTS</b>All eighteen anti-GABA B R 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.</p><p><b>CONCLUSIONS</b>Our study demonstrates that most Han Chinese patients with anti-GABA B R 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-GABA B R antibodies is necessary for patients with possible LE or new-onset epilepsy with unknown etiology.</p>

Ninety-day administration of dl-3-n-butylphthalide for acute ischemic stroke: a randomized, double-blind trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Dl-3-n-butylphthalide (NBP), first isolated from the seeds of celery, showed efficacy in animal models of stroke. This study was a clinical trial to assess the efficacy and safety of NBP with a continuous dose regimen among patients with acute ischemic stroke.</p><p><b>METHODS</b>A randomized, double-blind, double-dummy trial enrolled 573 patients within 48 hours of onset of ischemic stroke in China. Patients were randomly assigned to receive a 14-day infusion of NBP followed by an NBP capsule, a 14-day infusion of NBP followed by aspirin, or a 14-day infusion of ozagrel followed by aspirin. The efficacy measures were Barthel index score and the modified Rankin scale (mRS) at day 90. Differences among the three groups on mRS were compared using χ(2) test of proportions (with two-sided α = 0.05) and Logistic regression analysis was conducted to take the baseline National Institutes of Health Stroke Scale (NIHSS) score into consideration.</p><p><b>RESULTS</b>Among the 535 subjects included in the efficacy analysis, 90-day treatment with NBP was associated with a significantly favorable outcome than 14-day treatment with ozagrel as measured by mRS (P < 0.001). No significant difference was found among the three groups on Barthel index at day 90. The rate of adverse events was similar among the three groups.</p><p><b>CONCLUSIONS</b>The 90-day treatment with NBP could improve outcomes at the third month after stroke. The NBP treatment (both intravenous and oral) is safe (ChiCTR-TRC-09000483).</p>

Risk analysis for cerebral hyperperfusion syndrome after carotid endarterectomy / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze risk factors for cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy (CEA).</p><p><b>METHODS</b>From September 2010 to September 2012, 183 consecutive patients with carotid artery stenosis who had indications for CEA entered the study. There were 149 male and 34 female patients, aged from 38 to 83 years with an average of (66 ± 9) years. Intracranial blood flow changes were monitored through transcranial Doppler routinely. Pre- and post-operative middle cerebral artery velocity (VMCA) were recorded. CHS was diagnosed by the combination of hyperperfusion syndrome and 100% increase of VMCA after operation compared with pre-operative baseline values. The patients who had CHS during hospitalization were recorded. Pre-operative and operative related factors were analyzed by univariate analysis, followed by Logistic regression model, to identify the risk factors of CHS.</p><p><b>RESULTS</b>Overall, CHS occurred in 15 patients (8.2%) after CEA. The average onset time was (2.6 ± 0.2) days after surgery. By decreasing blood pressure and using dehydration medicine, all the patients with CHS recovered before discharge. None of them developed to intracranial hemorrhage. On univariate analysis, significant risk factors for CHS were history of stoke, symptomatic carotid artery stenosis and shunting during operation. On Logistic regression model, independent risk factor was symptomatic carotid artery stenosis (OR = 6.733, 95%CI: 1.455-31.155, P = 0.015), while shunting during operation (OR = 0.252, 95%CI: 0.067-0.945, P = 0.041) was a protective factor.</p><p><b>CONCLUSIONS</b>Symptomatic carotid artery stenosis is an independent risk factor for CHS after CEA and shunting during operation is a protective factor. Using shunt may be an effective method of preventing CHS after CEA.</p>