Analysis of epidemiological and clinical characteristics of 1247 cases of infectious diseases of the central nervous system / 解放军医学杂志

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

Prognostic value of time to generalization in 71 Chinese patients with sporadic amyotrophic lateral sclerosis / 中华医学杂志(英文版)

BACKGROUND@#It is important to determine prognostic factors for the outcome of amyotrophic lateral sclerosis (ALS) at an early stage. The time taken for symptoms to spread from spinal or bulbar regions to both (time to generalization; TTG) is considered a strong predictor of survival; however, this has rarely been studied in Asian populations. The aim of this retrospective study was to evaluate potential factors affecting prognosis in Chinese patients with sporadic ALS, with a focus on the association between TTG and overall survival.@*METHODS@#Seventy-one patients with sporadic ALS who were hospitalized at Chinese PLA General Hospital from 2009 to 2016 were followed up until December 2017. Survival analysis was performed using univariate Kaplan-Meier log-rank and multivariate Cox proportional hazards models. The clinical data of the patients were recorded and analyzed. Variables studied were age at symptom onset, sex, site of symptom onset, diagnostic latency, TTG, diagnostic category, ALS Functional Rating Scale-revised score, percent predicted forced vital capacity (FVC%), and disease progression rate (DPR) at diagnosis.@*RESULTS@#The mean age at onset was 54 (SD = 10.2) years, and the median survival time from symptom onset was 41 months (95% confidence interval: 34-47). By univariate analysis, factors independently affecting survival were age at symptom onset (Log rank = 15.652, P < 0.0001), TTG (Log rank = 14.728, P < 0.0001), diagnostic latency (Log rank = 11.997, P = 0.001), and DPR (Log rank = 6.50, P = 0.011). In the Cox multivariate model, TTG had the strongest impact on survival time (hazard ratio = 0.926, P = 0.01).@*CONCLUSIONS@#TTG can be used as an effective indicator of prognosis in patients with sporadic ALS.

Prognostic value of time to generalization in 71 Chinese patients with sporadic amyotrophic lateral sclerosis / 中华医学杂志(英文版)

Background:@#It is important to determine prognostic factors for the outcome of amyotrophic lateral sclerosis (ALS) at an early stage. The time taken for symptoms to spread from spinal or bulbar regions to both (time to generalization; TTG) is considered a strong predictor of survival; however, this has rarely been studied in Asian populations. The aim of this retrospective study was to evaluate potential factors affecting prognosis in Chinese patients with sporadic ALS, with a focus on the association between TTG and overall survival.@*Methods:@#Seventy-one patients with sporadic ALS who were hospitalized at Chinese PLA General Hospital from 2009 to 2016 were followed up until December 2017. Survival analysis was performed using univariate Kaplan-Meier log-rank and multivariate Cox proportional hazards models. The clinical data of the patients were recorded and analyzed. Variables studied were age at symptom onset, sex, site of symptom onset, diagnostic latency, TTG, diagnostic category, ALS Functional Rating Scale-revised score, percent predicted forced vital capacity (FVC%), and disease progression rate (DPR) at diagnosis.@*Results:@#The mean age at onset was 54 (SD = 10.2) years, and the median survival time from symptom onset was 41 months (95% confidence interval: 34–47). By univariate analysis, factors independently affecting survival were age at symptom onset (Log rank = 15.652, P < 0.0001), TTG (Log rank = 14.728, P < 0.0001), diagnostic latency (Log rank = 11.997, P = 0.001), and DPR (Log rank = 6.50, P = 0.011). In the Cox multivariate model, TTG had the strongest impact on survival time (hazard ratio = 0.926, P = 0.01).@*Conclusions:@#TTG can be used as an effective indicator of prognosis in patients with sporadic ALS.

Repetitive Nerve Stimulation in Amyotrophic Lateral Sclerosis / 中华医学杂志(英文版)

<p><b>Background</b>Nowadays, it is widely known that decremental responses in low-frequency repetitive nerve stimulation (LF-RNS) are frequently observed in patients with amyotrophic lateral sclerosis (ALS). The pathological mechanism of this phenomenon remains unknown. This study aimed to illuminate the features of RNS in Chinese patients with ALS.</p><p><b>Methods</b>Clinical and electrophysiological data of 146 probable and definite ALS patients who underwent RNS were retrospectively enrolled and analyzed. LF-RNS (3 Hz) was performed in trapezius, deltoid, abductor digiti minimi (ADM), quadriceps femoris, and tibialis anterior. High-frequency RNS (HF-RNS, 10 Hz) was performed only in ADM. The two-sample t-test and Chi-squared test were used for statistical analysis.</p><p><b>Results</b>Decremental responses to LF-RNS (≥10%) in at least one muscle were detected in 83 (56.8%) of the cases and were most commonly seen in trapezius and deltoid. The incidence of decremental response was higher in patients with upper limb onset. Incremental responses to HF-RNS (≥60%) in ADM were observed in 6 (5.6%) of the cases. In 106 muscles with decremental response, 62 (57.4%) muscles had a continuous decremental pattern, more than a U-shape pattern (37 cases, 34.3%). Nineteen cases showed definite decrements in LF-RNS tests in trapezius, while no abnormalities were found in the electromyography and neurological examination of the sternocleidomastoid muscle, supplied by the accessory nerve as well.</p><p><b>Conclusions</b>Decremental responses in the RNS are commonly observed in ALS patients. The findings regarding the trapezius indicated that some ALS onsets could be initiated by a "dying back" process, with destruction of neuromuscular junctions (NMJs) before motor neurons. Incremental responses in the ADM implied damage of the NMJs involved both the post and presynaptic membranes.</p>

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>

Clinical Characteristics, Electrophysiology, and Skin Biopsy of 38 Peripheral Neuropathy Cases with Small Fiber Involvement of Various Etiologies / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In small fiber neuropathy (SFN), thinly myelinated Aδ and unmyelinated C fibers are primarily affected, resulting in sensory and/or autonomic symptoms. Various etiologies have been shown to be associated with SFN. This study was aimed to analyze a variety of features in peripheral neuropathy (PN) with small fiber involvement, and to compare disease severity among patients with idiopathic PN, PN associated with impaired glucose tolerance (IGT), and metabolic syndrome (MS) PN.</p><p><b>METHODS</b>Thirty-eight PN patients with small fiber involvement were enrolled from December 20, 2013 to May 31, 2016. Patients were divided into idiopathic PN, IGT-related PN, and MS-related PN groups. Detailed medical history and small fiber neuropathy were investigated, and symptom inventory questionnaire was conducted, as well as the visual analog scale. Nerve conduction studies and skin biopsies were also performed. The differences among the groups were analyzed using analysis of variance and Kruskal-Wallis test.</p><p><b>RESULTS</b>Eight patients were diagnosed with pure SFN. Intraepidermal nerve fiber density (IENFD) weakly correlated with motor conduction velocity (MCV) (r = 0.372, P = 0.025), and proximal (r = 0.383, P = 0.021) and distal (r = 0.358, P = 0.032) compound muscle action potential (CMAP) of the tibial nerve. IENFD also weakly correlated with MCV of the peroneal nerve (r = 0.399, P = 0.016). IENFD was shown to be significantly different among all groups (χ2 = 9.901, P = 0.007). IENFD was significantly decreased (χ2 = 23.000, P = 0.003) in the MS-related PN group compared to the idiopathic PN group. The MCV of the tibial nerve was significantly different among all groups (χ2 = 8.172, P < 0.017). The proximal (F = 4.336, P = 0.021) and distal (F = 3.262, P = 0.049) CMAP of the tibial nerve was also significantly different among all groups.</p><p><b>CONCLUSIONS</b>IENFD of patients included in the present study weakly correlated with various electrophysiological parameters. Small and large fibers are more involved in patients with MS-related PN than in patients with idiopathic PN.</p>

Effects of Head-down Tilt on Nerve Conduction in Rhesus Monkeys / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Few studies have focused on peripheral nerve conduction during exposure to microgravity. The -6° head-down tilt (HDT) comprises an experimental model used to simulate the space flight environment. This study investigated nerve conduction characteristics of rhesus monkeys before and after prolonged exposure to HDT.</p><p><b>METHODS</b>Six rhesus monkeys (3-4 years old) were tilted backward 6° from the horizontal. Nerve conduction studies (NCSs) were performed on the median, ulnar, tibial, and fibular motor nerves. Analysis of variance with a randomized block design was conducted to compare the differences in the NCS before and 7, 21, and 42 days after the -6° HDT.</p><p><b>RESULTS</b>The proximal amplitude of the CMAP of the median nerve was significantly decreased at 21 and 42 days of HDT compared with the amplitude before HDT (4.38 ± 2.83 vs. 8.40 ± 2.66 mV, F = 4.85, P = 0.013 and 3.30 ± 2.70 vs. 8.40 ± 2.66 mV, F = 5.93, P = 0.004, respectively). The distal amplitude of the CMAP of the median nerve was significantly decreased at 7, 21, and 42 days of HDT compared with the amplitude before HDT (7.28 ± 1.27 vs. 10.25 ± 3.40 mV, F = 4.03, P = 0.039; 5.05 ± 2.01 vs. 10.25 ± 3.40 mV, F = 6.25, P = 0.04; and 3.95 ± 2.79 vs. 10.25 ± 3.40 mV, F = 7.35, P = 0.01; respectively). The proximal amplitude of the CMAP of the tibial nerve was significantly decreased at 42 days of HDT compared with the amplitude before HDT (6.14 ± 1.94 vs. 11.87 ± 3.19 mV, F = 5.02, P = 0.039).</p><p><b>CONCLUSIONS</b>This study demonstrates that the compound muscle action potential amplitudes of nerves are decreased under simulated microgravity in rhesus monkeys. Moreover, rhesus monkeys exposed to HDT might be served as an experimental model for the study of NCS under microgravity.</p>

Mutation Analysis of Gap Junction Protein Beta 1 and Genotype-Phenotype Correlation in X-linked Charcot-Marie-Tooth Disease in Chinese Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Among patients with Charcot-Marie-Tooth disease (CMT), the X-linked variant (CMTX) caused by gap junction protein beta 1 (GJB1) gene mutation is the second most frequent type, accounting for approximately 90% of all CMTX. More than 400 mutations have been identified in the GJB1 gene that encodes connexin 32 (CX32). CX32 is thought to form gap junctions that promote the diffusion pathway between cells. GJB1 mutations interfere with the formation of the functional channel and impair the maintenance of peripheral myelin, and novel mutations are continually discovered.</p><p><b>METHODS</b>We included 79 unrelated patients clinically diagnosed with CMT at the Department of Neurology of the Chinese People's Liberation Army General Hospital from December 20, 2012, to December 31, 2015. Clinical examination, nerve conduction studies, and molecular and bioinformatics analyses were performed to identify patients with CMTX1.</p><p><b>RESULTS</b>Nine GJB1 mutations (c.283G>A, c.77C>T, c.643C>T, c.515C>T, c.191G>A, c.610C>T, c.490C>T, c.491G>A, and c.44G>A) were discovered in nine patients. Median motor nerve conduction velocities of all nine patients were < 38 m/s, resembling CMT Type 1. Three novel mutations, c.643C>T, c.191G>A, and c.610C>T, were revealed and bioinformatics analyses indicated high pathogenicity.</p><p><b>CONCLUSIONS</b>The three novel missense mutations within the GJB1 gene broaden the mutational diversity of CMT1X. Molecular analysis of family members and bioinformatics analyses of the afflicted patients confirmed the pathogenicity of these mutations.</p>

Familial and sporadic distal myopathy with rimmed vacuoles: comparison of the clinical, pathological, laboratory test and follow-up data / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the clinical, pathological, laboratory test and follow-up data between familial and sporadic patients with distal myopathy with rimmed vacuoles (DMRV) and discuss the characteristics of this disorder in Chinese population.</p><p><b>METHODS</b>The clinical and pathological features, laboratory data and follow-up results of 33 sporadic and 4 familial cases of pathologically confirmed DMRV were summarized and compared retrospectively.</p><p><b>RESULTS</b>The patients age, onset age, or disease duration showed no significant difference between sporadic and familial cases; the onset pattern and affected muscle groups were also similar, but the sporadic cases showed more frequent dysmorphic features than the familial cases. The patients showed mild to moderate elevation of the muscle enzymes by one to three folds, and the familial patients had more significant elevation than the sporadic ones. No correlation was found between the disease duration and the level of muscle enzymes. The pathological findings were similar between the cases, and Gomori staining showed rimmed vacuoles and inclusion bodies without inflammatory cell infiltration. Follow-up results of 29 cases showed no significant difference between the two groups. The disease was slowly progressive and severely affected the quality of life of the patients, but did not produce obvious effect on the life expectancy.</p><p><b>CONCLUSION</b>The clinical, pathological and laboratory data of Chinese DMRV patients are basically similar to those of Japanese cases. Sporadic cases tend to show more dysmorphic features than the familial ones, and occasional sporadic cases have early disease onset in early childhood.</p>

Different clinical features of single and multiple cerebral venous thromboses / 中华神经医学杂志

Objective To discuss the different clinical features and prognosis of single cerebral venous thrombosis (CVT) and multiple CVT. Methods The site and the number of vein and thrombosed sinuses of 136 patients with CVT were summarized. The patients were divided into 2 groups according to the numbers of thrombosed sinuses. The clinical features and outcome of the patients with single CVT were analyzed in comparison with those with multiple CVT by univariate analysis. Results In 44 patients (32.4%), only 1 cerebral sinus was involved. In 92 patients (67.6%), 2 or more cerebral veins and sinuses were involved (2 sinuses in 45, 3 sinuses in 35, 4 sinuses in 9, 5 sinuses in 3). The lateral sinus and the sigmoid sinus were the most frequent thrombosed sinuses which were found in 86.8% of patients; the followings were superior sagittal sinus (58.1%), straight sinus (18.4%) , deep venous system (7.4%), and cortical veins (2.9%). Mean ages were significantly older but the short-term prognosis was better in the group of patients with single CVT in comparison with those in the group of patients with multiple CVT. The patients with multiple CVT also presented more serious intracranial hypertension, more frequent parenchymal lesions and systematic thrombotic events than those with single CVT (P＜0.05). Conclusion In most CVT patients, 2 or more veins and sinuses are involved and thromboses most commonly implicate the lateral sinus and the superior sagittal sinus. Patients with multiple CVT usually present higher intracranial pressure, more serious clinical course, worse outcome and higher incidence of systematic venous thrombotic events in comparison with patients with single CVT. And the multiple sinus thrombosis is more likely to cause venous infarctions and intracranial hemorrhage than the single one.

Acute panautonomic neuropathy: a report of 4 cases / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the clinical manifestations, diagnosis, treatment and prognosis of acute panautonomic neuropathy (APN).</p><p><b>METHODS</b>We reviewed the history, clinical findings, electrophysiological characteristics, laboratory features of CSF and treatment of 4 patients with APN.</p><p><b>RESULTS</b>All these patients showed acute onset with apparent involvement of the autonomic nervous system. The clinical features of autonomic involvement included fixed dilated pupils, abdominal pain, diarrhea, and anhidrosis. Electromyography showed evidence of peripheral neuropathy. Early treatment with corticosteroid and intravenous immunoglobulins resulted in improved prognosis of the patients.</p><p><b>CONCLUSION</b>APN is a rare autonomic nervous system disorder, and understanding of the clinical features may help in early diagnosis and treatment of the patients.</p>

Value of tumor markers in the cerebrospinal fluid in the diagnosis of meningeal carcinomatosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the diagnostic value of tumor markers in the cerebrospinal fluid (CSF) for meningeal carcinomatosis (MC).</p><p><b>METHODS</b>Twenty-one MC patients (including 13 adenocarcinoma and 8 non-adenocarcinoma patients), 72 patients with tuberculous meningitis (TBM) and 23 with primary intracerebral tumors (PIT) were enrolled in this study. Blood and CSF tumor markers including CEA, CA125, CA15-3, CA19-9, CA72-4, CYFRA21-1, AFP and NSE were measured by Roche E170 electrochemiluminescence analyzer and sandwich assay.</p><p><b>RESULTS</b>CSF tumor markers CEA, CA125, CA199 and CYFRA21-1 and the serum tumor markers CEA, CA125, CA153, CA199 and AFP were significantly higher in MC group than in the other two groups. CSF CEA and CA15-3 were significantly higher in adenocarcinoma MC than in non-adenocarcinoma MC patients, but no significant differences were found in the serum tumor markers between the two groups (P>0.05). CSF tumor markers including CEA, CA125, CA15-3, CA72-4 and CYFRA21-1 were positively correlated to the serum tumor markers (P<0.05). CA199 was positively correlated to the disease course (P<0.05), and age was not correlated to any of the indexes (P>0.05).</p><p><b>CONCLUSION</b>Detection of the tumor markers in the CSF, especially CEA, CA125, CA19-9 and CYFRA21-1, may help in the early diagnosis of MC. CEA and CA15-3 can serve as indicators for differential diagnosis of adenocarcinoma and non-adenocarcinoma.</p>

Analysis of nerve conduction abnormalities in POEMS syndrome / 中华神经医学杂志

Objective To elucidate the electrophysiological features of POEMS syndrome. Methods We retrospectively analyzed the electrophysiological findings of 22 patients of POEMS, and compared their results with those of 22 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Results Compared with the CIDP group, the motor nerve conduction velocity was decreased in the POEMS group, but the difference was not significantstatistically (P>0.05); whereas, distal motor latency (DML) was significantly decreased (P<0.05), and terminal latency index (TLI) was significantly increased (P<0.05). The incidence rate of the nerve conduction block in the POEMS group was lower than that in the CIDP group (P<0.05). Compound muscle action potential (CMAP) of the tibial nerve was decreased significantly in the POEMS group as compared with the CIDP group (P<0.05), whereas CMAP of the median nerve was not significantly different (P>0.05). Abnormal electrophysiology was frequently observed in muscles of lower limbs in the POEMS group, and in comparison of upper limbs, the difference was not significant statistically (P<0.05).Conclusion In POEMS syndrome, slowing of nerve conduction velocity is more predominant in the intermediate segments of the peripheral nerve, and conduction block is rare. Abnormal nerve conduction may be correlated with limbs.