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Objective:To evaluate the significance of copy number variation (CNV) and metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) in the diagnosis of meningeal carcinomatosis (MC).Methods:Ten patients with MC diagnosed in the Department of Neurology of Peking Union Medical College Hospital from March 2022 to June 2022 were consecutively enrolled in this study. The patients were diagnosed according to the criteria of the Chinese expert consensus on the diagnosis of MC by the Chinese Society of Infectious Diseases and Cerebrospinal Fluid Cytology, and the diagnosis of MC was confirmed by CSF cytology. The control group included 10 patients who were diagnosed as autoimmune encephalitis or viral encephalitis. CSF mNGS and CNV analysis were performed simultaneously in all the patients.Results:Of the 10 patients with MC, 6 had lung adenocarcinoma, 4 had breast cancer. CSF mNGS and CNV analysis detected large CNV in 8 of 10 patients with MC, including 4 patients with breast cancer and 4 patients with lung cancer. The results of pathogenic microorganism analysis of CSF mNGS in all the patients were negative. Meanwhile, large CNV was not detected in the control group.Conclusions:CSF CNV can serve as a diagnostic marker for MC. The combination of mNGS and CNV analysis has demonstrated a high positive rate in the diagnosis of MC. The dual-omics analysis of pathogenic microorganisms and CNV has been proposed as a potential strategy to further expand the clinical utility of CSF mNGS in the realm of auxiliary diagnosis.
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Objective:To explore the epidemiology, clinical features and prognosis of pseudorabies virus (PRV) infection in human.Methods:A case of human PRV encephalitis combined with acute retinal necrosis (ARN) in the First Affiliated Hospital of Zhengzhou University in May 2020 was reported. The epidemiology, clinical features, neuroimaging, cerebrospinal fluid (CSF), next-generation sequencing (NGS), treatment and prognosis of human PRV infection were summarized and analyzed with the previous published data.Results:The present case was a 38-year-old man who developed high fever, headache, cognitive decline, recurrent epileptic seizures after butchering a pig. Brain magnetic resonance imaging showed lesions in the insular lobes, temporal lobes, cingulate gyrus, frontal lobes, basal ganglia and hippocampus, with more significant signals on the left side. Afterwards, bilateral ARN occurred and resulted in his blindness. PRV DNA was detected from the aqueous humor. By literature review, a total of 20 cases (including this case) were analyzed. Most patients (95%, 19/20) had the history of direct contact with swine. The median incubation period was 7 days. The infection normally caused encephalitis (95%, 19/20), some cases with endophthalmitis (60%, 12/20). Based on the neuroimaging of the 19 patients, the lesions in neuroimaging were mainly in limbic system, especially in insular (17/19) and temporal lobes (17/19). The basal ganglia was often involved (9/19).The PRV-DNA was detected by NGS in CSF or intraocular fluid. Antiviral drugs and adjuvant treatment, including immunoglobulin and/or corticoid therapy, were effective to only few cases. Most patients (90%, 18/20) had the sequelae of severe impairment of daily living (modified Rankin Scale scores≥3).Conclusions:The cardinal clinical characteristics of human PRV infection are progressive panencephalitis and endophthalmitis, with an unfavorable outcome. The history of exposure to sick swine and typical neuroimaging suggest PRV infection. NGS of CSF and/or intraocular fluid is the dependable diagnostic method.
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Paraneoplastic neurological syndromes (PNS) are heterogeneous disorders caused by autoimmune responses of cancer, which can affect any part of the nervous system. Anti-amphiphysin antibody is one of the high-risk PNS antibodies, which is usually associated with small cell lung cancer and breast cancer. However, extrapulmonary neuroendocrine carcinoma is rare in patients with anti-amphiphysin antibody. A case of anti-amphiphysin-associated paraneoplastic brainstem encephalitis with esophageal neuroendocrine carcinoma is reported. The tumor was detected by fluorine 18 fluorodeoxyglucose positron emission tomography and pathologically confirmed by gastroscopic biopsy. The patient′s neurological symptoms were partially improved after treatment of intravenous immunoglobulin and glucocorticoids. However, the disease prognosis is closely related to the accompanying tumor.
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Viral encephalitis is one of the major neurological emergency and critical diseases. The clinical classification of encephalitis is an important basis for clinical etiological diagnosis. Virus nucleic acid detection of cerebrospinal fluid is the main diagnostic experiment of viral encephalitis, including polymerase chain reaction and metagenome next-generation sequencing. Specific antiviral drugs are effective for some types of viral encephalitis, and new therapeutic regimes need to be explored.
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Several anti-neural antibodies are associated with neuropsychiatric systemic lupus erythematosus (NPSLE) including anti-neuronal antibodies and anti-glial cell antibodies. The anti-neuronal antibodies has two types: anti-neuronal surface protein antibodies represented by anti-N-methyl-D-aspartate receptor (NMDAR) antibodies, and anti-neuronal intracellular protein antibodies. In this paper, we review and classify the anti-neural antibodies related to NPSLE.
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Objective To evaluate the clinical and paraclinical features of Chinese patients with anti- LGI1 encephalitis. Methods Patients with memory deficits, psychiatric symptoms, seizures or altered level of consciousness, suspicious of encephalitis, at presentation to Peking Union Medical College Hospital were recruited between July 2013 and January 2018, and tested for anti-LGI1 antibodies in their serum and/or cerebrospinal fluid(CSF) samples. Patients with anti-LGI1 antibodies were enrolled. The demographic characteristics, clinical manifestations, laboratory examination results, neuroimaging features, immunotherapy, follow-up practices and outcomes for included patients were registered and analyzed. Results The study enrolled 120 patients, of whom 66.7% were male. The median age was 61 years (interquartile range [IQR]: 49-66 years). Seizures(65.0%) were the most common initial symptoms. Most patients developed seizures (95.0%), including faciobrachial dystonic seizures (54.2%), memory deficits (92.5%), and psychiatric symptoms (69.1%). Brain MRI and 18F-FDG PET / CT showed that the lesions were mainly located in unilateral or bilateral medial temporal lobes, and (or) basal ganglia. Of the patients, 95.0% received intravenous immunoglobulin (IVIg) or corticosteroids, 47.5% received mycophenolate mofetil as long-term immunotherapy, and no one received second-line immunotherapy. The median follow-up was 34.2 months(IQR: 22.0-45.6 months). 91.2% had a good outcome (modified Rankin Scale score≤2 points). Residual mild memory deficits were present in 47.8% of the patients. Nine deaths were documented. Relapses occurred in 24.8% of the patients in the first year. In total, 24 (20%)cases were young patients(onset age ≤45 years).There were fewer males among the younger patients(37.5% vs. 74.0%, P < 0.01). Besides, there were fewer younger patients with psychiatric symptoms(50.0% vs. 74.0%, P=0.02), hyponatremia(33.3% vs. 68.8%, P < 0.01), and abnormalities on brain 18F-FDG PET/CT(20.8% vs. 47.9%, P=0.02). The relapse-free survival rate was significantly higher in the young patients. Conclusions Elderly males were predominant in patients with anti-LGI1 encephalitis. Most patients developed symptoms of limbic encephalitis and/or FDBS during the disease course. Several patients were young adults and lacked typical symptoms. Neuroimaging features were consistent with the involvement of limbic system or basal ganglia. Patients with anti-LGI1 encephalitis respond well to immunotherapy, irrespective of the age.
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Objective:To analyze and summarize the clinical characteristics of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients with cerebellar ataxia.Methods:The clinical manifestations, laboratory examinations, treatment and prognosis of anti-NMDAR encephalitis patients with cerebellar ataxia diagnosed and treated in Peking Union Medical College Hospital from 2011 to 2019 were retrospectively analyzed.Results:About 4.3% (15 cases) of a total of 347 anti-NMDAR encephalitis patients were complicated with cerebellar ataxia, of which one patient had ovarian teratoma. There were seven male cases and eight female cases, with a median age of 28 years. The average duration from the onset of encephalitis to the onset of cerebellar symptoms was 30.8 days.The average modified Rankin Scale (mRS) score was 3.73. In the acute phase, the median cerebrospinal fluid leukocyte count was 28×10 6/L. All patients received first-line immunotherapy, of which one case additionally received second-line immunotherapy with rituximab and nine patients received long-term immunotherapy with mycophenolate mofetil. The follow-up time ranged from seven to 66 months. The average mRS score of the last time was 2.73, and only six patients (6/15) had good prognosis (mRS score≤2). Conclusions:Patients with anti-NMDAR encephalitis and cerebellar ataxia are rare, and have relatively poor prognosis in terms of neurological function. Symptoms of cerebellar ataxia in anti-NMDAR encephalitis patients should be recognized in time, and standardized immunotherapy regimens and long-term immunotherapy should be adopted to improve the prognosis.
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Objective:To identify anti-dipeptidyl-peptidase-like protein 6 (DPPX) antibody in patients with encephalitis of unknown etiology and describe the clinical features of anti-DPPX antibody-associated encephalitis in Chinese patients.Methods:For patients registered in the Peking Union Medical College Hospital Encephalitis and Paraneoplastic Syndrome Registration Project from 2016 to 2019 with negative findings in autoimmune encephalitis routine antibody profile and paraneoplastic antibody profile, but with positive tissue-based assay (TBA) results, further tests for rare antibodies, including cell-based assay (CBA) of anti-DPPX antibody, were performed. Patients positive for anti-DPPX antibody were enrolled and the clinical data were collected.Results:Two patients with anti-DPPX antibody-associated encephalitis were found from 2016 to 2019 among about 15 000 patients. Both were females, aged 46 and 75 years. One patient had diarrhea, cachexia, cognitive dysfunction, agitation, myoclonus, tremor, and seizures. The other had cognitive impairment, restlessness, memory loss, disorientation, and sleep disturbance. The second patient had medical history of systemic lupus erythematosus and secondary Sj?gren′s syndrome.Conclusions:TBA should be combined with CBA in identification of anti-DPPX antibody to confirm the diagnosis. Anti-DPPX antibody-associated encephalitis has clinical manifestations of encephalopathy with diarrhea and cachexia, and can coexist with systemic lupus erythematosus.
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With the understanding of autoimmune encephalitis many novel types of autoimmune encephalitis and related antibodies have been identified. There are some cases of autoimmune encephalitis with autoantibody overlapping syndromes or phenotype overlapping syndromes, which bring challenges to diagnosis and treatment in practice. The relevant literature was reviewed and the clinical characteristics, pathological mechanism and treatment of overlapping syndromes associated with autoimmune encephalitis were summarized, in order to provide a reference for the management of autoimmune encephalitis with overlapping syndromes.
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Antibodies to glutamic acid decarboxylase (GAD) have been associated with several neurological syndromes, including stiff-person syndrome, cerebellar ataxia and epilepsy. This article critically reviews the main clinical characteristics and the evidence on the pathogenicity of GAD antibodies.
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Cerebellar ataxia mediated by autoimmune mechanisms is a common cause of sporadic cerebellar ataxia. According to the presence of underlining malignancy, autoimmune cerebellar ataxia (ACA) can be divided into paraneoplastic ACA and non-paraneoplastic ACA. The typical manifestations of various types of ACA include gait disorder, limb and trunk ataxia, mild inflammatory response and specific oligoclonal bands in cerebrospinal fluid. Immunosuppressive therapy might be effective. Anti-neuronal antibodies are of great significance to the diagnosis of ACA, and the discovery of the new antibody profile has promoted a deeper understanding of ACA. This article reviews the clinical features and progress of diagnosis and treatment of ACA.
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Standardization and individualization are two important aspects in the diagnosis and treatment of autoimmune encephalitis. The Chinese expert consensus on the diagnosis and management of autoimmune encephalitis (2017) is the major reference for neurological practice in China, while individualization of treatment is mainly based on the specific types of autoimmune encephalitis and the dynamic observation of clinical response and immune parameters. The results of recent clinical research provide evidence for new treatment strategy.
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Novel coronavirus pneumonia, also known as coronavirus disease 2019 (COVID-19), is caused by a new coronavirus that infects the lungs. Although some patients with COVID-19 may be combined with neurological symptoms, there is no direct evidence that this new coronavirus can directly invade nerve system. A case of COVID-19 with tuberculous meningitis is reported to remind that when patients with COVID-19 present symptom of encephalitis or meningitis, a comprehensive pathogen examination is recommended.
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Objective:To assess the clinical value of metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid in pathogenic diagnosis of neurological infectious disease.Methods:Patients who were clinically diagnosed with infectious encephalitis and meningitis and treated in Department of Neurology, Affiliated Hospital of Chifeng University from March 2018 to September 2019 were retrospectively analyzed, including the clinical characteristics and data of mNGS and traditional laboratory test of pathogens.Results:Totally 104 patients with infectious encephalitis and meningitis were eligible for enrollment, and mNGS detected 22 bacterial species(22/104,21.15%), 24 viral species (24/104,23.08%), one fungal species (1/104,0.96%), one parasitic species (1/104,0.96%) and one mycoplasma species (1/104,0.96%).The three leading positive detections were varicella-zoster virus ( n=19), streptococcus ( n=7) and Mycobacterium tuberculosis ( n=4). Combined with traditional pathogen detection methods, clinical manifestations, final diagnosis and treatment results, the number of cases diagnosed by mNGS was 49 cases. The positive rate of the mNGS was 47.12% (49/104).False positives occurred in 21 (20.19%) patients. False negatives occurred in 34 (32.69%) patients. Conclusions:mNGS is more sensitive in evaluating the pathogens causing the infectious encephalitis and meningitis. It has advantages in accurate diagnosis of infectious encephalitis and meningitis.
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COVID-19 is caused by a new coronavirus that infects the lungs. Although some patients with COVID-19 may be combined with neurological symptoms, there is no direct evidence that this new coronavirus can directly invade nerve system. A case of COVID-19 with tuberculous meningitis is reported to remind that when patients with COVID-19 present symptom of encephalitis or meningitis, a comprehensive pathogen examination is recommended.
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Standardization and individualization are two important aspects in the diagnosis and treatment of autoimmune encephalitis.The Chinese expert consensus on the diagnosis and management of autoimmune encephalitis (2017) is the major reference for neurological practice in China,while individualization of treatment is mainly based on the specific types of autoimmune encephalitis and the dynamic observation of clinical response and immune parameters.The results of recent clinical research provide evidence for new treatment strategy.
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Objective To establish a test of autoantibody-panel for the diagnosis of autoimmune cerebellitis (AC) and determine the prevalence of AC in patients with cerebellar ataxia of unknown etiology.Methods Autoantibody screening tests with indirect immunofluorescence were performed in serum and cerebrospinal fluid (CSF) samples of 400 previously'idiopathic'Chinese patients with cerebral ataxia (inpatients and outpatients in Peking Union Medical College Hospital or referred from hospitals of Beijing Encephalitis Group from 2016 to 2018).Immunotherapy was given to autoantibody positive patients and the effectiveness of immunotherapy was assessed.Detailed AC autoantibodies panel included anti-glutamate decarboxylase 65 (GAD65) antibody,anti-Tr (delta notch-like epidermal growth factor-related receptor (DNER)) antibody,anti-zinc finger protein 4 (ZIC4) antibody,anti-inositol 1,4,5-trisphosphate receptor 1 (ITPR1) antibody,anti-homer protein homolog 3 (Homer 3) antibody,anti-neurochondrin (NCDN) antibody,anti-carbonic anhydrase-related protein (CARP) antibody and anti-Purkinje cell antibody 2 (PCA2) antibody.Results Eight out of 400 (2％) ataxia patients were positive for this AC panel tests,of whom two were positive for anti-GAD65 antibody,two for anti-Tr antibody,one for anti-PCA2 antibody,one for anti-Homer 3 antibody and two were positive for serum anti-NCDN antibody.Autoantibodies against ZIC4,ITPR1 and CARP were not detected in this cohort.Two of the eight ataxia patients also presented with limbic encephalitis,and only one anti-GAD antibody patient was screened with underlying small cell lung carcinoma (SCLC).All the eight patients received immunotherapy and four experienced partial response.Conclusions Autoimmune cerebellitis is the cause of acquired cerebellar ataxia.Tests of autoantibodies associated with AC have diagnostic value for paraneoplastic and non-paraneoplastic cerebellar ataxia.Immunotherapy may yield partial response in patients with AC.
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Objective To analyze the clinical features of neurobrucellosis manifested as cerebrovascular diseases and explore the possible pathogenesis.Methods Cases of neurobrucellosis presenting as cerebrovascular diseases in Peking Union Medical College Hospital from January 2007 to February 2018 were analyzed retrospectively.The demographic information,epidemiological history,routine and etiology tests of blood and cerebrospinal fluid,imaging (magnetic resonance imaging + diffusion weighted imaging,magnetic resonance angiography/head and neck computed tomography angiography),echocardiography,treatment and prognosis of the above patients were collected.The possible mechanism of neurobrucellosis with cerebrovascular diseases was analyzed according to clinical manifestations and imaging characteristics.Results Totally,31 cases of neurobrucellosis were diagnosed,of which seven cases were mainly presented as cerebrovascular diseases (three cases as the first symptoms),accounting for 23％ of neurobrucellosis.There were three cases of cerebral infarction,one case of cerebral infarction accompanied with cerebral hemorrhage,one case of transient ischemic attacks (TIA),two cases of imaging abnormalities related to cerebral small vessel disease.Three patients were discharged voluntarily and four patients were treated with minocycline/doxycycline,rifampicin and ceftriaxone.The prognosis of the treatedcases was good.Conclusions Neurobrucellosis may be presented as TIA,cerebral infarction,cerebral hemorrhage or cerebral small vessel disease related imaging features.For cerebrovascular diseases with systemic nonspecific symptoms such as hearing loss and fatigue,it is necessary to differentiate Brucella infection.Vasospasm,vasculitis and infection-induced arteriosclerotic infarction may be the possible mechanism of stroke in these patients.
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Objective@#To summarize the clinical characteristics of Listeria monocytogenes meningitis (LMM) with complications, and analyze the outcomes of next generation sequencing.@*Methods@#Clinical characteristics, laboratory findings, imaging features, antibiotics treatment, and next generation sequencing of cerebrospinal fluid were analyzed in 3 LMM patients who were hospitalized in the Department of Infectious Diseases of Beijing Children′s Hospital Affiliated to Capital Medical University from July 2015 to November 2017.@*Results@#The three patients were 1-year-old girl, 2-year-old girl, and 9-year-old boy, with normal immune function. They had eaten refrigerated food, milk or dairy products before onset. Symptoms included fever, headache, abdominal pain, diarrhea, vomiting, and convulsions, etc. The complications of two cases (case 2 and 3) were appendicitis and Meckel′s diverticulitis. The other one (case 1) was with sepsis and pneumonia. Leukocyte counts in cerebrospinal fluid were elevated in all the three cases, and cranial magnetic resonance imaging showed meningeal or periventricular involvement. All the children were diagnosed with LMM by positive CSF culture. CSF for next generation sequencing was sent after carbapenem antibiotics using, yet all the results were positive. The positive results were returned 2, 9, and 9 days earlier than culture results, respectively. The gene coverage was 5.00%, 7.00%, 0.04%, and the reads was 2 561, 1 011 and 8, respectively. All the three children had recurrent fever despite using cephalosporin. Levels of leukocytes in the blood and CSF further elevated. After using carbapenem antibiotics, patients improved eventually and were discharged from hospital.@*Conclusions@#LMM can occur in children with normal immune function and is usually associated with digestive system symptoms. Listeria monocytogenes can be detected quickly and accurately by the next generation sequencing technology, without being limited to sampling time and antibiotics application.
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Objective@#To describe the clinical manifestations of central nerve system inflammatory demyelinating disease associated with anti-myelin oligodendrocyte glycoprotein antibody (MOG-IDD) in children, and to explore the clinical characteristics of the children.@*Methods@#The clinical and laboratory characteristics of the patients diagnosed in Beijing Children′s Hospital, Capital Medical University, from October 2016 to August 2018 were described, and the clinical data of the patients with unipolar and recurrent diseases were compared.@*Results@#A total of 50 patients were included, among whom the ratio of male to female was 24:26, and the average age of onset was (6.7±3.1) years old (0.4-12.6 years old). There was no significant difference in the age of onset between boys and girls(t=0.712, P=0.480). The main symptoms included fever (31/50 cases), encephalopathy (26/50 cases) and optic neuritis (22/50 cases), etc.In the last follow-up, 26 patients (52.0%) had a monophasic course and 24 patients (48.0%) had a recurrent course.There were age differences in encephalopathy and ataxia in the first episode of [(5.7±2.8) years old vs.(8.1±3.0) years old, (5.0±2.5) years old vs. (7.7±3.0) years old](t=2.746, P=0.009; t=2.837, P=0.007). The average number of recurrence was (2.1±1.4) times (1-7 times), in which 17 cases (70.8%) of recurrence presented within 12 months and 20 cases (83.3%) of recurrence presented within 24 months after onset.Convulsion incidences of recurrent cases were 10 cases and 13 cases respectively in the first episode and recurrent courses, which were significantly higher than those of monophasic cases (4 cases, 4 cases)(χ2=7.912, P=0.005; χ2=8.365, P=0.004). All patients were sensitive to first-line immunotherapy.Seven patients with recu-rrence were treated with mycophenolatemofetil, and 17 patients with repeated first-line therapy.In the last follow-up, all patients were in remission and 2 patients had mild neurological dysfunction.@*Conclusions@#MOG-IDD can occur in childhood.Encephalopathy and optic neuritis are the most common symptoms.Encephalopathy and ataxia are more common in young children.Convulsions may indicate the course of recurrence.