Coexistence of Autoimmune Encephalitis and Other Systemic Autoimmune Diseases.
Zhao Jing,Wang Cancan,Xu Xiaolu,Zhang Yuanxing,Ren Haitao,Ren Zhixia,Li Gai,Zhang Jiewen,Guan Hongzhi
Frontiers in neurology
In recent years, the phenomenon of coexisting systemic autoimmune diseases (ADs) in patients with autoimmune encephalitis (AE) has been increasingly found, while its clinical significance remains unexplored. This study aimed to investigate the types and potential clinical associations of autoimmune comorbidities in patients with antibody-positive AE. A retrospective cohort study of patients with antibody-positive AE was conducted from 2011 to 2018. The demographics, clinical characteristics, and follow-up data were reviewed. We enrolled 517 patients, among whom 45 were affected by one or more types of ADs, including Hashimoto's thyroiditis (HT) ( = 28), systemic lupus erythematosus (SLE) ( = 3), anaphylactoid purpura ( = 3), vitiligo ( = 3), Sjögren's syndrome (SS) ( = 2), chronic urticaria ( = 2), bullous pemphigoid ( = 1), uveitis ( = 1), myasthenia gravis (MG) ( = 1), and the coexistence of SLE and anaphylactoid purpura ( = 1). The proportion of patients with coexisting ADs was higher in those with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis than in those with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis (13/111 vs. 16/307) ( = 0.021). In anti-NMDAR and anti-LGI1 encephalitis patients, there were no significant differences in the age at onset, sex ratio, proportion of patients with tumors, disease severity, or recurrence between the groups with and without ADs. One or more types of ADs developed in AE patients, and patients with anti-LGI1 encephalitis had a higher frequency of autoimmune comorbidities than those with anti-NMDAR encephalitis. And we found that autoimmune comorbidities did not affect the clinical course of AE.
Autoantibodies in lupus: culprits or passive bystanders?
Rekvig Ole P,Putterman Chaim,Casu Cinzia,Gao Hua-Xin,Ghirardello Anna,Mortensen Elin S,Tincani Angela,Doria Andrea
Several autoantibodies are culprits in the pathogenesis of organ damage in systemic lupus erythematosus, by means of established or postulated mechanisms, whereby inducing a perturbation of cell structure and function, with consequent tissue-organ impairment. Common autoantibody-mediated mechanisms of damage include cell surface binding with or without cytolysis, immune complex-mediated damage, penetration into living cells, binding to cross-reactive extracellular molecules. Experimental data from both murine models and humans have recently clarified the key role of autoantibodies in severe organ involvements, including nephritis, neuropsychiatric (NP) dysfunction, and cerebrovascular disease (CVD). In lupus nephritis early and late phases are distinguishable and mediated by different processes in which anti-chromatin antibodies are both inducing and perpetuating agents, by immune-complex formation and massive deposition in mesangial matrix at first, and in glomerular basement membrane at end-stage. Also NP abnormalities occur very early, much earlier than other systemic manifestations, and exacerbate with the increase in autoantibody titers. Among the autoantibodies mainly implicated in neurolupus, anti-β2 glycoprotein I (β2GPI) antibodies are preferentially involved in focal NP events which are a consequence of non-inflammatory microangiopathy; otherwise, anti-ribosomal P protein antibodies and N-methyl-d-aspartate receptor (NMDAR) antibodies cause diffuse NP events through a direct cytotoxic effect on neuronal cells at specific brain zones.
Serum Systemic Autoantibodies in Anti-N-Methyl-D-Aspartate Receptor Encephalitis.
Zhang Bingjun,Yang Yu,Lin Yinyao,Ai Lulu,Men Xuejiao,Lu Zhengqi
Frontiers in neurology
The aim of this retrospective study was to investigate the relationship between serum systemic autoantibodies and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Thirty-nine patients with anti-NMDAR encephalitis were examined for serum systemic autoantibodies (antinuclear antibodies, extractable nuclear antigen autoantibodies, rheumatoid factors, and anti-neutrophil cytoplasmic antibodies), in comparison with 39 neuromyelitis optica spectrum disorder (NMOSD) and 78 healthy controls. Clinical features, cerebrospinal fluid characteristics, and outcomes were compared between the two subgroups of anti-NMDAR patients with positive and negative systemic autoantibodies, respectively. Anti-NMDAR encephalitis patients had higher frequency of positive serum systemic autoantibodies than healthy controls (23.1 vs. 2.6%, = 0.001) and lower frequency than NMOSD (23.1 vs. 48.7%, = 0.018). No patients were diagnosed comorbidities with non-organ-specific autoimmune diseases. Consciousness disturbance was more frequent in autoantibodies positive group than in the negative group (88.9 vs. 40.0%, = 0.02). Autoantibody positive group had a poorer outcome than autoantibody negative group (55.6 vs. 86.7%, = 0.043). There was a negative correlation between serum autoantibodies and outcomes in anti-NMDAR encephalitis patients ( = -0.325, = 0.044). Our data demonstrated serum systemic autoantibodies were more frequent in anti-NMDAR encephalitis patients than in healthy controls and less frequent than NMOSD, which were associated with higher severity of disease.
Clinical Characteristics of Anti--Methyl-d-Aspartate Receptor Encephalitis Overlapping with Demyelinating Diseases: A Review.
Frontiers in immunology
Anti--methyl-d-aspartate receptor encephalitis (NMDARe), a common autoimmune encephalitis, can be accompanied by demyelinating disorders, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). To compare the clinical characteristics of patients with different overlapping syndromes, we searched the PubMed database and performed a systematic review. Of the 79 patients with overlapping syndromes, 15 had MS, 18 had aquaporin-4-antibody-positive NMOSD (AQP4-Ab-positive NMOSD), and 46 had MOGAD. Compared with classical NMDARe, overlapping syndromes showed atypical symptoms, such as limb weakness, sensory disturbance, and visual impairments in addition to the main symptoms of NMDARe and a lower ratio of ovarian teratoma. Patients with MOGAD overlap were the youngest, while patients with MS and AQP4-Ab-positive NMOSD overlap tended to be older than patients with classical NMDARe. A majority of patients with NMDARe who overlapped with MS or AQP4-Ab-positive NMOSD were female, but this was not the case for patients overlapped with MOGAD. When NMDARe and demyelinating diseases occurred sequentially, the interval was the longest in patients with NMDARe overlapped with MS. A favorable outcome was observed in patients overlapping with MOGAD, but no robust comparison can be drawn with the patients overlapping with AQP4-Ab-positive NMOSD and MS regarding the small number of available data. The long-term prognosis of overlapping syndromes needs further investigation.
Validation of the Clinical Assessment Scale in Autoimmune Encephalitis in Chinese Patients.
Zhang Yingchi,Tu Ewen,Yao Chenxiao,Liu Jia,Lei Qiang,Lu Wei
Frontiers in immunology
Background and Objectives:The Clinical Assessment Scale in Autoimmune Encephalitis (CASE) is a scale for assessing severity in autoimmune encephalitis. We aimed to validate the CASE score in a Chinese population and evaluate its clinical significance. Methods:Patients diagnosed with autoimmune encephalitis were recruited between June 2014 and May 2019 from two hospitals. CASE and modified Rankin Scale (mRS) scores were obtained. Data regarding clinical features, treatment, and available information were gathered from the hospital information system. Results:Of the 176 patients with autoimmune encephalitis, 11 died and 14 had tumors. Ten patients received second-line treatment. The CASE scores of patients receiving second-line treatment were significantly higher (median CASE: 15) than in those receiving first-line treatment (median CASE: 8) (p<0.001). Twenty-two patients had poor functional status (mRS>2). Areas under the curve of CASE on whether functional status was poor at 1 year were 0.89 (p<0.001). Sixty patients were admitted to the intensive care unit (ICU), and the CASE scores were positively correlated with days in the ICU (r=0.58, p<0.001). There was no statistically significant association between the CASE scores and relapse (p=0.39>0.05). Additionally, the CASE scores were positively associated with the mRS scores (r=0.85 p<0.001). Conclusions:The CASE score is suitable for the comprehensive assessment of Chinese patients with autoimmune encephalitis, which may help clinicians to select the appropriate intervention and estimate the disease severity and prognosis.
Anti-NMDA receptor encephalitis: report of ten cases and comparison with viral encephalitis.
Gable M S,Gavali S,Radner A,Tilley D H,Lee B,Dyner L,Collins A,Dengel A,Dalmau J,Glaser C A
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
The California Encephalitis Project (CEP), established in 1998 to explore encephalitic etiologies, has identified patients with N-methyl-D-aspartate receptor (NMDAR) antibodies, the likely etiology of their encephalitis. This study compares the presentation of such patients to those with viral encephalitis, so that infectious disease clinicians may identify individuals with this treatable disorder. Patients were physician-referred, and standardized forms were used to gather demographic, clinical, and laboratory data. Features of anti-NMDAR+ patients were compared with the viral encephalitides of enteroviral (EV), rabies, and herpes simplex-1 (HSV-1) origins. Sixteen cases with confirmed viral etiologies were all negative on NMDAR antibody testing. Ten anti-NMDAR+ patients were profiled with a median age of 18.5 years (range 11-31 years). None were Caucasian. They had a characteristic progression with prominent psychiatric symptoms, autonomic instability, significant neurologic abnormalities, and seizures. Two had a teratoma, and, of the remaining eight, four had serologic evidence of acute Mycoplasma infection. The clinical and imaging features of anti-NMDAR+ patients served to differentiate this autoimmune disorder from HSV-1, EV, and rabies. Unlike classic paraneoplastic encephalitis, anti-NMDAR encephalitis affects younger patients and is often treatable. The association of NMDAR antibodies in patients with possible Mycoplasma pneumoniae infection warrants further study.
Clinical Study of Autonomic Dysfunction in Patients With Anti-NMDA Receptor Encephalitis.
Yan Lulu,Zhang Shuang,Huang Xiaoxue,Tang Yao,Wu Jun
Frontiers in neurology
Autonomic dysfunction is a common symptom of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis; however, it has been poorly researched. The purpose of this study was to compare the clinical features, tumor occurrence, intensive care unit (ICU) admission, mechanical ventilation, imaging assessment, cerebrospinal fluid examination, disease severity, and immunotherapy in patients with anti-NMDAR encephalitis with or without autonomic dysfunction. A retrospective study of anti-NMDAR encephalitis patients diagnosed between January 2016 and April 2020 was performed at the First Affiliated Hospital of Zhengzhou University. Patients were divided into two groups according to whether they had autonomic dysfunction, and their clinical features, treatment, and prognosis were compared. A total of 119 patients with anti-NMDAR encephalitis were included in this study. Seventy-three patients (61.3%) had autonomic dysfunction, while the remaining 46 (38.7%) did not. Sinus tachycardia (69.9%) was the autonomic dysfunction with the highest incidence, while the incidences of symptoms including constipation, central hypopnea, and others gradually decreased. Compared to the group without autonomic dysfunction, the prevalence of the main clinical symptoms such as epileptic seizure ( = 0.003), involuntary movement ( = 0.028), and decreased consciousness ( < 0.001) were higher in the group with autonomic dysfunction, which also more frequently presented with complications such as pulmonary infection ( < 0.001) and abnormal liver function ( = 0.001). Moreover, the rates of ICU admission ( < 0.001) and mechanical ventilation ( = 0.001), as well as the modified Rankin scale (mRS) scores at admission ( < 0.001), maximum mRS scores during the course of disease ( < 0.001), and mRS scores at discharge ( < 0.001) were higher in the patients with autonomic dysfunction than in those without. The number of patients in the autonomic dysfunction group who underwent ≥2 immunotherapies was also higher than that in the group without autonomic dysfunction ( < 0.001). Sinus tachycardia is the most common type of autonomic dysfunction in anti-NMDAR encephalitis. Compared to patients without autonomic dysfunction, those with autonomic dysfunction had a higher incidence of epilepsy, involuntary movements, decreased consciousness, pulmonary infections, abnormal liver function, ICU admissions, and mechanical ventilation; moreover, the severity of the disease was greater, and their prognosis worse. Therefore, such patients require intensive immunotherapy.
Influential factors and predictors of anti-N-methyl-D-aspartate receptor encephalitis associated with severity at admission.
Huang Xiao-Xue,Zhang Shuang,Yan Lu-Lu,Tang Yao,Wu Jun
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
OBJECTIVE:We aimed to study the clinical characteristics and biological indicators of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis with different severity levels to explore factors predicting disease severity at admission. METHODS:Using the modified Rankin scale (mRS), patients were divided into mild-to-moderate group (mRS ≤ 3) and severe group (mRS > 3) on admission based on severity of illness. General information, previous history, premonitory symptoms, clinical manifestations before admission, imaging findings and biochemical tests were compared to explore the clinical manifestations and biological indicators related to the severity of illness at admission. RESULTS:In the severe group, the incidences of fever, anti-infective therapy, generalized seizures, consciousness disorder, blood white blood cell, neutrophils, and neutrophil-lymphocyte ratio (NLR) were higher than those in mild-to-moderate group (P < 0.001, P = 0.001, P = 0.020, P < 0.001, P = 0.002, P < 0.001, P < 0.001, respectively); blood lymphocyte counts was lower than those in mild-to-moderate group (P < 0.001). There was the strongest significant positive correlation between the NLR and disease severity at admission (rs = 0.684, P < 0.001). In multivariate logistic regression, fever, generalized seizures, consciousness disorder, and elevated NLR were independent risk factors for disease severity; the area under the receiver operating characteristic curve was 0.896 (95%CI: 0.840-0.952, P < 0.001). CONCLUSION:Fever, generalized seizures, consciousness disorder, and elevated NLR were independent risk factors for disease severity. NLR is a good predictor of the severity of illness at admission.
Neutrophil Percentage-to-Albumin Ratio: A Good Parameter for the Evaluation of the Severity of Anti-NMDAR Encephalitis at Admission and Prediction of Short-Term Prognosis.
Frontiers in immunology
Objectives:The purpose of this study was to investigate the association of neutrophil percentage-to-albumin ratio (NPAR) with the severity at admission and discharge (short-term prognosis) in patients with anti-N-methyl-D-aspartic acid receptor (NMDAR) encephalitis. Methods:Multivariable logistic regression models such as NPAR were constructed based on univariable regression results. Receiver operating characteristic (ROC) curves, nomograms, and concordance index (c-index) were used to evaluate the efficacy of the models in assessing disease severity at admission and predicting short-term prognosis, validated by bootstrap, Hosmer-Lemeshow goodness-of-fit test, calibration curves, and decision curve analysis. Results:A total of 181 patients with anti-NMDAR encephalitis diagnosed at the First Affiliated Hospital of Zhengzhou University were included. The results showed that NPAR had good sensitivity and specificity in assessing disease severity at admission and predicting short-term prognosis. The multivariable logistic regression models based on NPAR and other influencing factors had good discrimination, consistency, accuracy, calibration ability, applicability, and validity in assessing the severity at admission and predicting short-term prognosis. Conclusion:NPAR has good clinical value in assessing disease severity at admission and predicting short-term prognosis of patients with anti-NMDAR encephalitis.
Relapse factors of patients of anti-N-methyl-D-aspartate receptor encephalitis.
Zhao Ying-Ying,Wang Hai-Xu,Wang Meng,Yuan Bo,Sun Tong-Wen,Xu Yu-Ming
Acta neurologica Scandinavica
BACKGROUND:The factors associated with anti-N-methyl-D-aspartate (NMDA) receptor encephalitis relapse are yet to be elucidated. AIMS OF THE STUDY:To investigate the factors associated with relapse and prognosis of anti-NMDA receptor encephalitis. METHODS:This retrospective study included patients diagnosed with anti-NMDA receptor encephalitis admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to October 2019. The clinical features, auxiliary examinations, treatment regimens, and follow-up were recorded. The outcomes were relapse and 2-year disease prognosis. RESULTS:A total of 160 patients were included. Consequently, 6 (5%) deaths, 34 (25.4%) relapses, and 19 (15.2%) patients had a poor prognosis (modified Rankin score (mRS) ≥3) were recorded. The multivariable analyses showed that age (p = .011), abnormal magnetic resonance imaging (MRI) (p = .019), glucocorticoid pulse (p = .009), and intracranial pressure (p = .023) were independently associated with the relapse, while age (p = .030) and central hypoventilation (p = .020) were independently associated with a poor prognosis at 2 years. CONCLUSION:Glucocorticoid pulse therapy reduces the relapse of anti-NMDA receptor encephalitis. Age, abnormal MRI, and intracranial pressure are risk factors for relapse, while age and central hypoventilation are independently associated with poor prognosis.
Neuromyelitis optica spectrum disorders with and without connective tissue disorders.
Yang Chun-Sheng,Zhang Qiu Xia,Chang Sheng Hui,Zhang Lin Jie,Li Li Min,Qi Yuan,Wang Jing,Sun Zhi Hua,Zhangning Nannan,Yang Li,Shi Fu-Dong
BACKGROUND:Neuromyelitis optica spectrum disorders (NMOSD) often coexist with connective tissue disorders (CTD). The aim of this study was to investigate and compare the features of NMOSD with and without CTD. METHODS:NMOSD patients with (n = 18) and without CTD (n = 39) were enrolled, and the clinical, laboratory, and magnetic resonance imaging (MRI) features of the two groups were assessed. RESULTS:Most of the demographic and clinical features examined were similar between NMOSD patients with and without CTD. Serum immunoglobulin G (IgG), percentage of γ-globulin and seropositivity for several other autoantibodies were significantly elevated in NMOSD patients with CTD (P < 0.05). NMOSD with CTD was marked by longer spinal cord lesions and a lower frequency of short transverse myelitis (TM) than NMOSD without CTD (P < 0.05). NMOSD with CTD also featured more T1 hypointensity and T2 bright spotty lesions (BSLs) on MRI than NMOSD without CTD (P = 0.001 and 0.011, respectively). There were no other differences in laboratory, MRI and clinical characteristics between different NMOSD subtypes. CONCLUSIONS:A few characteristics differed between NMOSD with and without CTD. NMOSD patients with CTD had higher serum IgG, longer spinal cord lesions, a lower frequency of short TM and more T1 hypointensity and T2 BSLs on spinal MRI than NMOSD patients without CTD.
[Clinical characteristics in 40 patients with longitudinally extensive transverse myelitis and connective tissue disease].
Zhang Y,Zhao J L,Yin H X,Xu Y,Zeng X F,Cui L Y
Zhonghua nei ke za zhi
Longitudinally extensive transverse myelitis (LETM) could be seen in patients with connective tissue disease (CTD), especially systemic lupus erythematosus (SLE) or primary Sjögren's syndrome (pSS). Some patients are combined with neuromyelitis optica spectrum disorders (NMOSD)(termed CTD-LETM-NMOSD) while others without (termed CTD-LETM-non-NMOSD). The aim of this study is to compare the clinical characteristics of CTD-LETM-NMOSD patients to CTD-LETM-non-NMOSD patients. We retrospectively collected data from 40 CTD patients with LETM who were admitted to the Department of Neurology or Rheumatology at Peking Union Medical College Hospital from Jan, 2006 to Dec, 2016. They were divided into CTD-LETM-NMOSD and CTD-LETM-non-NMOSD two groups. Demographic characteristics, clinical and laboratory features were obtained from the database. Relapse rates and clinical outcome were analyzed by Kaplan-Meier method. Among 40 patients with CTD, 28 (70.0%) were NMOSD while 12 (30.0%) were not. The positivity rates of anti-SSA, antibodies to aquaporin-4 (anti-AQP4) were significantly higher in patients with NMOSD than those in patients with non-NMOSD (<0.05). Age, gender, clinical features, disease duration, anti-double-stranded DNA antibody, anti-ribosomal P antibody, antiphospholipid antibodies, expanded disability status scale (EDSS) scores, and magnetic resonance imaging (MRI) features were all comparable between two groups. CTD-NMOSD patients had significantly higher disease relapse rate (75.0% vs. 3/12, <0.01). Anti-SSA and anti-AQP4 positivity is associated with NMOSD and higher relapse rates, which suggests that NMOSD in CTD-LETM patients may represent distinct characteristics and pathogenesis from patients with CTD-LETM-non NMOSD.
Incidence of neuromyelitis optica spectrum disorder (NMOSD) in China: A national population-based study.
The Lancet regional health. Western Pacific
BACKGROUND:Neuromyelitis Optica Spectrum Disorder (NMOSD) is an inflammatory disease of the central nervous system with preferential involvement of the optic nerve and spinal cord. However, data on NMOSD incidences in China, a country encompassing 20% of the world's population and covering vast areas of Eastern Asia, are unknown. METHODS:We conducted the first nationwide survey of NMOSD, based on the database of the National Hospital Quality Monitoring System (HQMS) of China, which covers all 1665 tertiary hospitals. The "Medical Record Homepage" of all patients were consistently collected via a standard protocol across each tertiary hospital. The primary outcome was the incidence of NMOSD, diagnosed according to the 2015 International Panel for Neuromyelitis Optica Diagnosis criteria and identified by ICD-10 code (G36•0). Burden of hospitalization, comorbidities, and death were also evaluated. FINDINGS:We identified 33,489 hospital admissions for 17,416 NMOSD diagnosed patients from 2016 to 2018. 11,973 patients were newly diagnosed NMOSD. The age and sex adjusted incidence per 100,000 person years was 0•278 (95% confidence interval [CI], 0•273-0•283), with 0•075 (0•069-0•08) in child and 0•347 (0•34-0•353) in adult. The peak age of onset NMOSD is 45-65 years with an incidence 0•445/100,000 (95% CI, 0•433-0•457). The female to male ratio was 4•71 (<0•001, 95% CI, 4•50-4•94). Geographical distribution of NMOSD is not related to the latitude gradient. Sjögren's syndrome (1,124/17,416, 6•5%) and systemic lupus erythematosus (387/17,416, 2•2%) are the most frequently autoimmune comorbidities. 106 adults and 4 children of the 17,416 NMOSD cohort died. INTERPRETATION:The incidence of NMOSD in China per 100,000 person years was 0•278, with 0•075 in child and 0•347 in adult. The geographical distribution of NMOSD is not related to the latitude gradient. FUNDING:National Science Foundation of China (91949208, 91642205, and 81830038); Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing.
The association between the lymphocyte-monocyte ratio and disease activity in rheumatoid arthritis.
Du Juping,Chen Shuaishuai,Shi Jianfeng,Zhu Xiaoli,Ying Haijian,Zhang Ying,Chen Shiyong,Shen Bo,Li Jun
The lymphocyte-monocyte ratio (LMR) is a systemic inflammatory marker for prediction of disease development, progress, and survival. Recently, a genome-wide association study identified genetic variations in ITGA4 and HLA-DRB1 that affect the LMR levels and were widely believed to be susceptibility genes for autoimmune diseases, including rheumatoid arthritis (RA). However, the role of LMR in RA patients remains unclear. The LMR level and other laboratory data of 66 RA patients, 163 osteoarthritis (OA) patients, and 131 healthy controls (HC) were compared using binary logistic regression. The correlations between LMR and disease activity and other inflammatory markers were measured using the Spearman rank test. ROC curve analyses assessed the diagnostic accuracy of LMR in RA. The LMR and lymphocyte count were significantly lower in RA patients, whereas the monocyte count was significantly higher relative to the HC group/OA patients (p < 0.01). A decreased LMR has been associated with increased disease activity (p = 0.012). In addition, the DAS28 and traditional inflammatory markers, including ESR, CRP, RDW, PLR, and NLR, and immune-related factors, such as C4, IgA, and IgM, were inversely correlated with LMR, while hemoglobin and albumin were positively correlated with LMR. The ROC curve showed that the area under the curve of LMR was 0.705 (95%CI = 0.630-0.781). The corresponding specificity and sensitivity were 82.82 and 45.45%, respectively. The present study shows that the LMR is an important inflammatory marker which could be used to identify disease activity in RA patients and to distinguish RA from OA patients.
Aquaporin-4-IgG positive neuromyelitis optica spectrum disorder and systemic autoimmune diseases overlap syndrome: a single-center experience.
Martín-Nares E,Hernandez-Molina G,Fragoso-Loyo H
OBJECTIVE:To describe the clinical and radiological characteristics and outcomes of patients with aquaporin-4-immunoglobulin G (AQP4-IgG) seropositive neuromyelitis optica spectrum disorder (NMOSD) coexisting with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) in a single center. METHODS:We included patients with diagnosis of NMOSD and a concomitant diagnosis of SLE or pSS. Demographic, clinical, serological and imaging characteristics were retrieved from clinical charts. RESULTS:Twelve patients were included, of whom 11 (91.7%) were women. Seven (58.3%) had SLE and five (41.7%) pSS. In five (41.7%) patients NMOSD followed SLE/pSS onset, four (33.3%) patients had a simultaneous presentation, and in three (25%) NMOSD preceded pSS onset. The mean age at first neurological event was 39 years. Eleven patients (91.7%) experienced acute transverse myelitis/longitudinally extensive transverse myelitis, five (41.7%) optic neuritis, three (25%) a cerebral syndrome and two (16.7%) each area postrema syndrome, acute brainstem syndrome and cerebellar syndrome. Eleven (91.7%) patients went into either total or partial NMOSD remission at median follow-up of 89.5 months. CONCLUSION:AQP4-IgG seropositive NMOSD arose in the context of quiescent SLE and pSS with extraglandular features. As NMOSD coexisting with SLE/pSS is rare, collaborative multicenter studies are needed to clarify the natural history and outcomes of this overlap syndrome.
Neuromyelitis Optica Spectrum Disorders (NMOSD) and Connective Tissue Disease (CTD): an Update for the Rheumatologist.
Cruz Roberto A,Chaudhary Sana,Guevara Myriam,Meltzer Ethan
Current rheumatology reports
PURPOSE OF REVIEW:To review the pathophysiology, presentation, and treatment of neuromyelitis optica spectrum disorder (NMOSD) and its association with systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS). RECENT FINDINGS:NMOSD is an autoimmune disorder of the central nervous system that primarily targets astrocytes. Although the prevalence is unknown, the coexistence of NMOSD and SLE/SS is well-recognized. Patients with both NMOSD and SLE or SS require may require unique approaches to diagnosis and management. Coexistence of NMOSD and SLE/SS is important for the rheumatologist and neurologist to be able to recognize. For the rheumatologist, NMOSD and its neurologic symptoms represent a distinct disease process from neurologic complications of the patient's underlying connective tissue disease, and it requires distinct acute and chronic management. For the neurologist, the coexistence of SLE and SS can help to establish a diagnosis of NMOSD, or in some situations, the development of neurologic symptoms secondary to NMOSD can lead to the diagnosis of connective tissue disease.
The Relationship Between Serum YKL-40 Levels on Admission and Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke.
Journal of inflammation research
BACKGROUND:Stroke-associated pneumonia (SAP) is a standout complication after acute ischemic stroke (AIS), with a prevalence of 7-38%. The aim of this prospective study was to investigate the relationship between serum YKL-40 levels at admission and SAP. METHODS:Between August 2020 and February 2021, consecutive AIS patients from two centers were enrolled prospectively. Serum YKL-40 concentrations were measured via enzyme-linked immunosorbent assay. We performed logistic regression analyses to explore the relationship between YKL-40 and SAP. Receiver operating characteristic curve was also used to assess the predictive ability of YKL-40 in predicting SAP. RESULTS:Ultimately, a total of 511 AIS patients were recruited. Multivariate logistic regression analysis showed that YKL-40 was independently related to SAP, whether as a continuous variable or as quartiles (=0.001). The area under curve of YKL-40 to predict SAP was 0.765. The optimal cutoff value of YKL-40 as a predictor of SAP was determined to be 206.4 ng/mL, where the sensitivity was 63.1% and the specificity was 82.0%. CONCLUSION:Our study demonstrated that YKL-40 might be considered as a useful biomarker to predict SAP in AIS patients.
YKL-40--a novel biomarker in clinical practice?
Kazakova Maria H,Sarafian Victoria S
YKL-40 is a recently discovered human glycoprotein which is related in amino acid sequence to the chitinase protein family, but has no chitinase activity. The present review focuses on the expression and regulation of YKL-40, its clinical significance, detection techniques and outlines the advantages and limitations of its application as a novel biomarker. YKL-40 is expressed and secreted by macrophages, neutrophils, fibroblast-like synovial cells, chondrocytes, vascular smooth muscle cells and hepatic stellate cells. The complete biological function of YKL-40 is unclear, and it is not yet known to have a specific receptor. However, its pattern of expression is associated with pathogenic processes related to inflammation, extracellular tissue remodeling, fibrosis and solid carcinomas. It is assumed that YKL-40 plays a role in cancer cell proliferation, survival, invasiveness and in the regulation of cell-matrix interactions. It is suggested that YKL-40 is a marker associated with a poorer clinical outcome in genetically defined subgroups of different tumors. YKL-40 was recently introduced into clinical practice and its application is still restricted. There are a few techniques available for its detection and the commercially accessible kits are limited, too. Elucidation of YKL-40 functions is an important objective of future studies as it seems likely that YKL-40 might have a significant role in cancer invasiveness and could possibly serve as an attractive target in anticancer therapy.
[The importance of determining the prognostic marker YKL-40 in serum and tissues].
Łata Ewelina,Gisterek Iwona,Matkowski Rafał,Szelachowska Jolanta,Kornafel Jan
Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego
YKL-40 is detected in the early nineties not only a glycoprotein secreted by cancer cells, but also of neutrophils, chondrocytes and endothelial cells. Biological function of YKL-40 are not exactly known, it is suggested that this protein participates in many physiological and pathological processes such as proliferation, angiogenesis, mitogenesis and remodelling. It is also a factor antyapoptotic and growth factor for some cells. Increased levels of YKL-40 in serum have been described in many diseases running with inflammation such as rheumatoid arthritis, systemic lupus erythematosus and Crohn's disease, and also in the group of cardiovascular diseases. Determination of the concentration of serum YKL-40 was also used in oncology. The tumors at various sites were found elevated levels of this marker in serum, as well as overexpression in tumor tissue. It was observed that higher titers YKL-40 levels are associated with shorter overall survival and disease-free period. It is suggested that measuring the concentration of YKL-40 in serum and its expression in tumor tissues may serve as a valuable and independent prognostic factor.
Diverse pathological implications of YKL-40: answers may lie in 'outside-in' signaling.
Prakash Mansi,Bodas Manish,Prakash Divya,Nawani Neelu,Khetmalas Madhukar,Mandal Abul,Eriksson Cecilia
The developing paradigms about YKL-40, a member of the "mammalian chitinase-like proteins", from across the globe, project it as a vital parameter for the detection of disease onset and progression. It is expressed and secreted by cancer cells of different origins along with a variety of non-malignant cells including inflammatory and structural cells. Numerous studies demonstrate that YKL-40 over-expression is associated with increased patient mortality though the cellular receptors responsible for mediating these effects have not yet been identified. The putative YKL-40 ligands are thought to be carbohydrate structures, since it is capable of binding chitin, chito-oligosaccharides and heparin. Binding of collagen to YKL-40, identified it as the only non-carbohydrate extracellular matrix (ECM) ligand for YKL-40. Our broad understanding of YKL-40 as a versatile biomarker and its involvement in activating several signaling pathways make us anticipate that its specific receptors/binding partners may exist on the cell surface also. The cell surface heparan sulfate (HS) moieties seem to be the potential candidates for this role, suggesting that it could interact with HS-proteoglycans. It is recommended to clearly delineate YKL-40-mediated signaling mechanisms before promoting the YKL-40 know-how for translational research, in both diagnostic and therapeutic applications. The present review provides an overview of YKL-40 as a versatile biomarker, discussing the related pathological mechanisms and aims to reassess and unify the already proposed diverse hypotheses in YKL-40-regulated signaling mechanisms.
A Direct Correlation between Red Blood Cell Indices and Cognitive Impairment After Aneurysmal Subarachnoid Hemorrhage (aSAH).
Gong Li,Gu Yongzhe,Dong Qiong,Zhang Xiang,Wang Haichao,Zhao Yanxin,Liu Xueyuan
Current neurovascular research
BACKGROUND:Cognitive impairment can occur after aneurysmal subarachnoid hemorrhage (aSAH) though it commonly tends to be neglected. Red blood cell (RBC) indices are associated with long-term functional outcomes, while it is unclear whether RBC indices could be a potential predictor of cognitive decline after aSAH. We aimed to investigate the association between RBC indices and post-aSAH cognitive impairment at 1 year. METHODS:Patients with aSAH received neuropsychological test by the Montreal Cognitive Assessment (MoCA) and underwent serum and cerebrospinal fluid (CSF) samples test. To determine the association between RBC indices and cognitive impairment after acute aSAH, we adjusted for demographic and vascular risk factors using multivariate logistic regression analysis. RESULTS:Of the 126 patients included in this study, 33% (42/126) of them were diagnosed with cognitive impairment (MoCA＜26). After adjustment for potential confounders, increased mean corpuscular volume (MCV) (OR: 1.36, 95%CI: 1.19-1.55) and mean corpuscular hemoglobin (MCH) (OR: 1.61, 95%CI: 1.25-2.08), reflecting systemic iron status, are more likely to be associated with cognitive impairment after aSAH. CONCLUSION:In this aSAH population, our data shows the positive association between MCH and MCV and cognitive impairment at 1 year.
Cognitive deficits among patients surviving aneurysmal subarachnoid hemorrhage. A contemporary systematic review.
British journal of neurosurgery
BACKGROUND:Subarachnoid hemorrhage (SAH) is associated with high rates of morbidity, including neurological and cognitive deficits that may be difficult to identify and quantify. This review provides an update on the cognitive deficits that may result from spontaneous aneurysmal SAH (aSAH) and identifies factors that may help predict and manage these deficits at discharge and thereafter. MATERIALS AND METHODS:We conducted a systematic review of PubMed and Google Scholar to identify studies published between 2010 and 2019 that assessed cognitive deficits at discharge and during follow-up in patients with aSAH. Full-text articles were assessed for information regarding cognitive testing and factors that may be associated with functional outcomes in this population. RESULTS:We reviewed 65 studies published since 2010 that described the cognitive deficits associated with non-traumatic aSAH. Such deficits may impact functional outcomes, quality of life, and return to work and may result in cognitive impairments, such as memory difficulties, speech problems, and psychiatric disorders. CONCLUSIONS:Patients with aSAH, even those that appear normal at the time of hospital discharge, may harbor cognitive deficits that are difficult to detect, yet can interfere with daily functioning. Further research is needed to provide additional information and to identify stronger correlations to be used in the identification, treatment, and amelioration of long-term cognitive deficits in aSAH patients, including those who are discharged with good clinical outcomes scores.
YKL-40 is elevated in cerebrospinal fluid from patients with purulent meningitis.
Østergaard Christian,Johansen Julia S,Benfield Thomas,Price Paul A,Lundgren Jens D
Clinical and diagnostic laboratory immunology
YKL-40, a member of the family 18 glycosyl hydrolases, is secreted by activated neutrophils and macrophages. It is a growth factor for connective tissue cells and a potent migration factor for endothelial cells and may function in inflammation and tissue remodeling. YKL-40 was determined in 134 cerebrospinal fluid (CSF) samples taken on admission from patients suspected of having meningitis (48 with purulent meningitis, 49 with lymphocytic meningitis, 5 with encephalitis, and 32 without evidence of meningitis). YKL-40 levels in CSF were significantly higher in patients with purulent meningitis (median, 663 microg/liter [range, 20 to 8,960]) and encephalitis (5,430 microg/liter [620 to 11,600]) than in patients with lymphocytic meningitis (137 microg/liter [41 to 1,865]) or patients without meningitis (167 microg/liter [24 to 630]) (Kruskal-Wallis and Dunn multiple comparison tests, P < 0.001). CSF YKL-40 levels were also determined for 26 patients with purulent meningitis having a repuncture, and patients who died (n = 5) had significantly higher YKL-40 levels than patients who survived (n = 21) (2,100 microg/liter [1,160 to 7,050] versus 885 microg/liter [192 to 15,400], respectively; Mann-Whitney test, P = 0.018). YKL-40 was most likely locally produced, since patients with infections of the central nervous system had CSF YKL-40 levels that were at least 10-fold higher than the corresponding levels in serum (2,033 microg/liter [470 to 11,600] versus 80 microg/liter [19 to 195]). The CSF neopterin level was the biochemical parameter in CSF and blood that correlated best with CSF YKL-40 levels, indicating that YKL-40 may be produced by activated macrophages within the central nervous system. In conclusion, high levels of YKL-40 in CSF are found in patients with purulent meningitis.
Astrocyte and macrophage regulation of YKL-40 expression and cellular response in neuroinflammation.
Bonneh-Barkay Dafna,Bissel Stephanie J,Kofler Julia,Starkey Adam,Wang Guoji,Wiley Clayton A
Brain pathology (Zurich, Switzerland)
Numerous inflammatory conditions are associated with elevated YKL-40 expression by infiltrating macrophages. Thus, we were surprised to observe minimal macrophage and abundant astrocyte expression of YKL-40 in neuroinflammatory conditions. The aims of the current study were to better delineate this discrepancy, characterize the factors that regulate YKL-40 expression in macrophages and astrocytes and study whether YKL-40 expression correlates with cell morphology and/or activation state. In vitro, macrophages expressed high levels of YKL-40 that was induced by classical activation and inhibited by alternative activation. Cytokines released from macrophages induced YKL-40 transcription in astrocytes that was accompanied by morphological changes and altered astrocytic motility. Because coculturing of astrocytes and macrophages did not reverse this in vitro expression pattern, additional components of the in vivo central nervous system (CNS) milieu must be required to suppress macrophage and induce astrocyte expression of YKL-40.
Expression of oligodendroglial and astrocytic lineage markers in diffuse gliomas: use of YKL-40, ApoE, ASCL1, and NKX2-2.
Rousseau Audrey,Nutt Catherine L,Betensky Rebecca A,Iafrate A John,Han Moonjoo,Ligon Keith L,Rowitch David H,Louis David N
Journal of neuropathology and experimental neurology
The phenotypic heterogeneity of astrocytic and oligodendroglial tumor cells complicates establishing accurate diagnostic criteria, and lineage-specific markers would facilitate diagnosis of glioma subtypes. Based on data from the literature and from expression microarrays, we selected molecules relevant to gliogenesis and glial lineage specificity and then used immunohistochemistry to assess expression of these molecules in 55 diffuse gliomas, including 8 biphasic oligoastrocytomas, 21 oligodendrogliomas (all with 1p/19qloss), 21 astrocytomas, and 5 glioblastomas. For the astrocytic lineage markers (GFAP, YKL-40, and ApoE), GFAP expression was significantly higher in the astrocytic component of oligoastrocytomas compared with the oligodendroglial part; similar patterns were detected for YKL-40 and ApoE, although the differences were not significant. GFAP, YKL-40, and ApoE reliably distinguished grade II-III oligodendrogliomas from grade II-IV astrocytomas (p < 0.0001, p = 0.002, and p < 0.0001, respectively). Among the oligodendroglial lineage markers (Olig2, Sox10, ASCL1, and NKX2-2), ASCL1 and NKX2-2 displayed significantly different immunostaining between oligodendrogliomas and astrocytomas (p = 0.017 and 0.004, respectively), but none clearly differentiated between the 2 glial populations of oligoastrocytomas. In addition to GFAP, therefore, YKL-40, ApoE, ASCL1, and NKX2-2 represent promising tumor cell markers to distinguish oligodendrogliomas from astrocytomas.
Serum neurofilament light chain as outcome marker for intensive care unit patients.
Fisse Anna Lena,Pitarokoili Kalliopi,Leppert David,Motte Jeremias,Pedreiturria Xiomara,Kappos Ludwig,Gold Ralf,Kuhle Jens,Yoon Min-Suk
Journal of neurology
OBJECTIVE:Neurofilament light chain (NfL) in serum indicates neuro-axonal damage in diseases of the central and peripheral nervous system. Reliable markers to enable early estimation of clinical outcome of intensive care unit (ICU) patients are lacking. The aim of this study was to investigate, whether serum NfL levels are a possible biomarker for prediction of outcome of ICU patients. METHODS:Thirty five patients were prospectively examined from admission to ICU until discharge from the hospital or death. NfL levels were measured longitudinally by a Simoa assay. RESULTS:NfL was elevated in all ICU patients and reached its maximum at day 35 of ICU treatment. Outcome determined by modified Rankin Scale at the end of the follow-up period correlated with NfL level at admission, especially in the group of patients with impairment of the central nervous system (n = 25, r = 0.56, p = 0.02). CONCLUSION:NfL could be used as a prognostic marker for outcome of ICU patients, especially in patients with impairment of the central nervous system.
Serum YKL-40 levels as a prognostic factor in patients with intracerebral hemorrhage.
Jiang Yi-Xiang,Zhang Gui-Hong,Wang Zhi-Min,Yang Hui
OBJECTIVES:This study aimed to investigate the relationship between serum YKL-40 concentrations and 3-month clinical outcomes in patients with intracerebral hemorrhage. DESIGN AND METHODS:In 172 consecutive patients and 172 sex- and age-matched healthy controls, serum YKL-40 concentrations were measured with an enzyme-linked immunoassay. The prognostic value of YKL-40 concentrations for 3-month mortality and functional outcome was assessed. An unfavorable outcome was defined as a score above 2 on the modified Rankin Scale. RESULTS:Serum concentrations of YKL-40 were markedly higher in all patients than in healthy controls, and were correlated positively with National Institute of Health Stroke Scale scores and plasma C-reactive protein levels. YKL-40 was identified as an independent predictor of 3-month mortality and unfavorable outcome and its area under receiver operating characteristic curve was similar to the National Institute of Health Stroke Scale scores. However, it did not improve the prognostic predictive performance of National Institute of Health Stroke Scale score. CONCLUSIONS:YKL-40 is associated with inflammation and severity of intracerebral hemorrhage, and may independently predict long-term clinical outcomes of intracerebral hemorrhage.
Serum neurofilament light chain in pediatric MS and other acquired demyelinating syndromes.
Wong Yu Yi M,Bruijstens Arlette L,Barro Christian,Michalak Zuzanna,Melief Marie-José,Wierenga Annet F,van Pelt E Daniëlle,Neuteboom Rinze F,Kuhle Jens,Hintzen Rogier Q
OBJECTIVE:To explore the correlation between serum and CSF neurofilament light chain (NfL) and the association of NfL levels and future disease activity in pediatric patients with a first attack of acquired demyelinating syndromes (ADS). METHODS:In total, 102 children <18 years with a first attack of CNS demyelination and 23 age-matched controls were included. Clinically definite multiple sclerosis (CDMS) was set as an endpoint for analysis. CSF NfL was tested by the commercially available ELISA (UmanDiagnostics); serum NfL (sNfL) was tested with a Simoa assay. Hazard ratios (HR) were calculated with Cox regression analysis. RESULTS:Of the 102 patients, 47 (46%) were tested for CSF NfL. CSF and serum NfL correlated significantly in the total group (ρ 0.532, < 0.001) and even more significantly in the subgroup of patients with future CDMS diagnosis (ρ 0.773, < 0.001). sNfL was higher in patients than in controls (geometric mean 6.1 pg/mL, < 0.001), and was highest in ADS presenting with encephalopathy (acute disseminated encephalomyelitis, n = 28, 100.4 pg/mL), followed by patients without encephalopathy (ADS-) with future CDMS diagnosis (n = 40, 32.5 pg/mL), and ADS- who remained monophasic (n = 34, 17.6 pg/mL). sNfL levels higher than a median of 26.7 pg/mL at baseline are associated with a shorter time to CDMS diagnosis in ADS- ( = 0.045). HR for CDMS diagnosis was 1.09 for each 10 pg/mL increase of sNfL, after correction for age, oligoclonal bands, and MRI measures ( = 0.012). CONCLUSION:The significant correlation between CSF and serum NfL strengthens its reliability as a peripheral marker of neuroaxonal damage. Higher sNfL levels at baseline were associated with higher probability of future CDMS diagnosis in ADS-.
Spinal cord infarction and patent foramen ovale: is there a link?
Mendonça Marcelo,Correia Ana Sofia,Luís Ana,Soares Pedro,Calado Sofia,Viana-Baptista Miguel
Case reports in neurology
Spinal cord infarction (SCI) is an uncommon but important cause of acute myelopathy. Nevertheless, contrary to cerebral stroke, the discussion about paradoxical embolism as a cause of cryptogenic SCI remains dubious. We describe the case of a 24-year-old woman who developed sudden-onset back pain followed by upper limb paralysis. T2-weighted MRI demonstrated hyperintense signal, extending from C5 to D1 with corresponding restricted diffusion on diffusion-weighted MRI and reduction of the apparent diffusion coefficient. Diagnostic workup, including lumbar puncture, showed no changes. Transcranial Doppler showed a right-to-left shunt with an uncountable number of microembolic signals after Valsalva maneuvers, and a patent foramen ovale (PFO) with an atrial septum aneurysm was identified. We discuss the paucity of evidence of right-to-left shunting in spinal diseases compared to cerebral events and the potential role of paradoxical embolism through PFO as a possible mechanism of SCI.
The styloid process and the formation of sigmoid sinus diverticulum: is there a link?
Brazilian journal of otorhinolaryngology
INTRODUCTION:Sigmoid sinus diverticulum has been considered the most common cause of pulsatile tinnitus; the mechanism underlying sigmoid sinus diverticulum formation is unclear. To the best of our knowledge, no previous studies have assessed whether the formation of sigmoid sinus diverticulum is related to compression of the internal jugular vein by the styloid process. OBJECTIVE:To discuss the relationship between the styloid process and the formation of sigmoid sinus diverticulum. METHODS:The medical records of nine patients diagnosed with venous pulsatile tinnitus caused by sigmoid sinus diverticulum were reviewed between April 2009 and May 2019. All patients underwent high-resolution computed tomography of the temporal bones, computed tomography venogram of the head and neck, magnetic resonance venography, and brain magnetic resonance imaging. The length and medial angulation of the styloid process were measured, and compression of the internal jugular vein was recorded. RESULTS:The study population consisted of nine female right-sided pulsatile tinnitus patients with a mean age of 53.8±4.6 years. The mean lengths of the styloid process were 3.9±0.6cm on the right side and 4.1±0.7cm on the left side. The mean medial angulation of the styloid process was significantly smaller on the right side than the left side (65.3°±1.2° vs. 67.8°±1.7°, p<0.05). In addition, computed tomography venogram of the head and neck demonstrated the left internal jugular vein was compressed by the styloid process in eight of the nine patients. CONCLUSION:The formation of sigmoid sinus diverticulum with venous pulsatile tinnitus may be related to compression of the contralateral internal jugular vein by the styloid process. However, accumulation of data in additional cases is required to verify this suggestion.
Worldwide Incidence and Prevalence of Neuromyelitis Optica: A Systematic Review.
Papp Viktoria,Magyari Melinda,Aktas Orhan,Berger Thomas,Broadley Simon A,Cabre Philippe,Jacob Anu,Kira Jun-Ichi,Leite Maria Isabel,Marignier Romain,Miyamoto Katsuichi,Palace Jacqueline,Saiz Albert,Sepulveda Maria,Sveinsson Olafur,Illes Zsolt
OBJECTIVE:Since the last epidemiologic review of neuromyelitis optica/neuromyelitis optica spectrum disorder (NMO/NMOSD), 22 additional studies have been conducted. We systematically review the worldwide prevalence, incidence, and basic demographic characteristics of NMOSD and provide a critical overview of studies. METHODS:PubMed, Ovid MEDLINE, and Embase using Medical Subject Headings and keyword search terms and reference lists of retrieved articles were searched from 1999 until August 2019. We collected data on the country; region; methods of case assessment and aquaporin-4 antibody (AQP4-Ab) test; study period; limitations; incidence (per 100,000 person-years); prevalence (per 100,000 persons); and age-, sex-, and ethnic group-specific incidence or prevalence. RESULTS:We identified 33 relevant articles. The results indicated the highest estimates of incidence and prevalence of NMOSD in Afro-Caribbean region (0.73/100 000 person-years [95% CI: 0.45-1.01] and 10/100 000 persons [95% CI: 6.8-13.2]). The lowest incidence and prevalence of NMOSD were found in Australia and New Zealand (0.037/100 000 person-years [95% CI: 0.036-0.038] and 0.7/100,000 persons [95% CI: 0.66-0.74]). There was prominent female predominance in adults and the AQP4-Ab-seropositive subpopulation. The incidence and prevalence peaked in middle-aged adults. African ethnicity had the highest incidence and prevalence of NMOSD, whereas White ethnicity had the lowest. No remarkable trend of incidence was described over time. CONCLUSION:NMOSD is a rare disease worldwide. Variations in prevalence and incidence have been described among different geographic areas and ethnicities. These are only partially explained by different study methods and NMO/NMOSD definitions, highlighting the need for specifically designed epidemiologic studies to identify genetic effects and etiologic factors.
The differential expression of natural killer cells in NMOSD and MS.
Ding Jie,Zhu De-Sheng,Hong Rong-Hua,Wu Yi-Fan,Li Ze-Zhi,Zhou Xia-Jun,Cai Jian,Guan Yang-Tai
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
Natural killer (NK) cells are involved in the pathogenesis of inflammatory demyelinating diseases of the central nervous system. However, the differential expressions of NK cells in the peripheral blood of patients with neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) are unknown. This study aimed to explore the differential expressions of NK cells in NMOSD and MS and evaluate the clinical implications of this difference. We performed a cross-sectional study to investigate the expression of NK cells in the peripheral blood of patients with NMOSD (n = 78) and MS (n = 24) and of healthy controls (HC, n = 27). Furthermore, we investigated the relationship between NK cell level and disease phase in 102 patients with NMOSD and MS through Spearman correlation analysis and receiver operating characteristic (ROC) analysis. Our results showed that the median (interquartile range) NK cell levels in acute-phase NMOSD patients, remission-phase NMOSD patients, acute-phase MS patients, and HC subjects were 114.10 (64.75-153.38) cells/µL, 167.60 (116.35-266.15) cells/µL, 282.55 (140.57-368.20) cells/µL, and 221.00 (170.40-269.55) cells/µL, respectively (p < 0.001). The Spearman correlation coefficient (95%) for the relationship between NK level and disease phase in NMOSD patients was 0.366 (0.150-0.550) (p < 0.001). Furthermore, ROC analysis revealed that patients with NK cell values lower than 172.200 cells/µL were more prone to have acute-phase NMOSD than MS. In conclusion, the expression of NK cells in peripheral blood was lower in patients with NMOSD than in patients with MS in the acute phase, and a low expression of NK cells may suggest having acute-phase NMOSD rather than MS.
Clinical predictive factors for diagnosis of MOG-IgG and AQP4-IgG related paediatric optic neuritis: a Chinese cohort study.
Yang Mo,Wu Yiqun,Lai Mengying,Song Honglu,Li Hongen,Sun Mingming,Xie Lindan,Zhou Huanfen,Xu Quangang,Wei Shihui,Wu Weiping
The British journal of ophthalmology
BACKGROUND:Different glial-autoantibodies-related paediatric optic neuritis (ON) are associated with different clinical characteristics and prognosis that require different treatments. Because glial autoantibody detection is not available in some parts of the world and there is often a delay in obtaining results, clinical factors that can be used to predict the subtype of paediatric ON are needed. METHODS:This was a single-centre retrospective cohort study. Children who presented with their first ON attack and with complete clinical data were included in the analysis. Single and multiple parameters for predicting paediatric myelin oligodendrocyte glycoprotein immunoglobin-associated ON (MOG-ON) and aquaporin-4 immunoglobin-related ON (AQP4-ON) were calculated. RESULTS:78 paediatric patients had their first ON attack from January 2016 to December 2019, of whom 69 were included in the final analysis, including 33 MOG-ON cases, 17 AQP4-ON cases and 19 Seronegative-ON cases. For predicting paediatric MOG-ON, the most sensitive predictors were 'male or optic disc swelling (ODS) or bilateral' (sensitivity 0.97 (95% CI 0.82 to 1.00)) and 'follow-up visual acuity (VA) ≤0.1 logMAR or ODS' (sensitivity 0.97 (95% CI 0.82 to 1.00)), and the most specific factor was 'Age ≤11 y and simultaneous CNS involvement' (specificity 0.97 (95% CI 0.84 to 1.00)). For predicting paediatric AQP4-ON, the most sensitive predictor was 'Female or without ODS' (sensitivity 1.00 (95% CI 0.77 to 1.00)), and the most specific factors were Neurological history (sensitivity 0.94 (95% CI 0.83 to 0.98)) and follow-up VA >1.0 logMAR (sensitivity 0.96 (95% CI 0.86 to 0.99)). CONCLUSION:According to our data from a Chinese paediatric cohort, using multiple parameters increases the sensitivity and specificity of diagnosing paediatric MOG-ON and AQP4-ON. These can assist clinicians in diagnosing and treating paediatric ON when glial autoantibody status is not available.
[Retrospective study of clinical features of neuromyelitis optica spectrum disease with connective tissue disease].
Zhang Yao,Fei Yunyun,Niu Jingwen,Ren Haitao,Zhao Jiuliang,Wang Qian,Xu Yan
Zhonghua yi xue za zhi
OBJECTIVE:To explore the clinical features of neuromyelitis optica (NMO) spectrum disease (NMOSD) with connective tissue disease (CTD). METHODS:The clinical features of 184 NMO/NMOSD patients (NMO/NMOSD: 119/184, 64.7%; NMO/NMOSD-CTD: 65/184, 35.3%) from May 2013 to May 2014 were analyzed retrospectively. And the effectiveness of long-term treatment of immunosuppressive drugs in NMOSD was evaluated. RESULTS:NMO/NMOSD-CTD patients had significantly higher female percentage (93.8% vs 83.2%, P < 0.05) and significantly higher percentage of patients with cerebral spinal fluid (CSF)-restricted oligoclonal band (OB)(41.5% vs 21.9%, P < 0.05). As compared with NMO/NMOSD-CTD counterparts, NMO/NMOSD patients had significantly higher percentage of non-specific lesions on brain MRI (62.5% vs 35.9%, P < 0.01). After >6 months consecutive long-term treatment of immunosuppressive drugs, the relapse rate post-treatment (0.36 ± 0.85) was significantly lower than that pre-treatment (2.91 ± 4.10, P < 0.01). And no significant difference existed in expanded disability status scale (EDSS) score between pre-and post-treatment. When using azathioprine (AZA), the percentage of relapse was significantly higher in NMO/NMOSD-CTD patients (50.0%) versus NMO/NMOSD ones (18.5%, P = 0.064); When using cyclophosphamide (CTX), there was no such significant difference. CONCLUSION:Female patients are more susceptible to have NMO/NMOSD with CTD. NMO/NMOSD-CTD patients tend to have higher percentage of CSF-restricted OB and fewer non-specific lesions on brain MRI. AZA and CTX may effectively reduce relapses in both NMO/NMOSD and NMO/NMOSD-CTD patients. However CTX is superior to AZA for reducing relapses in NMO/NMOSD-CTD patients.
[Clinical Features of Neuromyelitis Optica Spectrum Disorders with Connective Tissue Diseases].
Xie Jia Yi,Chen Xiao Qing,Zhou Ming Xuan,Ye Li Chao
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae
Objective To investigate the clinical features of neuromyelitis optica spectrum disorders(NMOSD)with connective tissue diseases(CTD). Methods Clinical data of 16 NMOSD-CTD patients and 54 NMOSD patients admitted to the Second Affiliated Hospital of Fujian Medical University from January 2015 to February 2020 were collected.The initial symptom,intracranial lesion,spinal cord lesion,laboratory examination and treatment response were compared between the two groups. Results The incidence of Sjögren's syndrome(SS)was the highest(10/16,62.5%)in NMOSD-CTD group.The NMOSD-CTD group had significantly higher positive rate of aquaporin-4 immunoglobulin G(AQP4-IgG)in serum or cerebrospinal fluid(100% vs. 70.2%,P=0.009),higher positive rates of serum anti-nuclear antibodies,anti Sjögren's syndrome A antibodies and anti-Ro52 autoantibodies(P<0.001),as well as higher proportion of patients with the expanded disability status scale score ≥ 6(50.0% vs. 22.2%,P=0.035)than the NMOSD group.There was no significant difference between the two groups in the age of onset,visiting age,recurrence frequency,disease course,distribution of intracranial lesions,spinal cord involvement,or the effective rate of glucocorticoid pulse therapy(all P>0.05).Conclusions NMOSD is often complicated with CTD,and SS is the most common one.The positive rate of serum or cerebrospinal AQP4-IgG and the seropositivity of several other autoantibodies in NMOSD-CTD patients were higher than those in NMOSD patients.Neurological impairment in NMOSD-CTD patients were severer,which should arouse attention of clinicians.
Autoimmune diseases associated with Neuromyelitis Optica Spectrum Disorders: A literature review.
Shahmohammadi Sareh,Doosti Rozita,Shahmohammadi Abootorab,Mohammadianinejad Seyed Ehsan,Sahraian Mohammad Ali,Azimi Amir Reza,Harirchian Mohammad Hossein,Asgari Nasrin,Naser Moghadasi Abdorreza
Multiple sclerosis and related disorders
INTRODUCTION:Neuromyelitis Optica (NMO) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) which predominantly involves optic nerves and spinal cord. Since the introduction of Neuromyelitis Optica Spectrum Disorders (NMOSD) as a separate entity, there have been many reports on its association with other disorders including systemic and organ-specific autoimmune diseases. Here, we reviewed other immune-mediated diseases associated with NMOSD and tried to categorize them. METHODS:The present review was conducted using the PUBMED database based on papers from 1976 (i.e., since the first NMO comorbidity with SLE was reported) to 2017. We included all articles published in English. The keywords utilized included Neuromyelitis optica, Neuromyelitis Optica Spectrum Disorders, Devic's disease, in combination with comorbidity or comorbidities. RESULTS:Diseases with immune-based pathogenesis are the most frequently reported co-morbidities associated with NMOSD, most of which are antibody-mediated diseases. According to literature, Sjogren's Syndrome (SS) and Systemic Lupus Erythematosus (SLE) are the most frequently reported diseases associated with NMOSD among systemic autoimmune diseases. Further, myasthenia gravis in neurological and autoimmune thyroid diseases in non-neurological organ-specific autoimmune diseases are the most reported comorbidities associated with NMOSD in the literature. CONCLUSIONS:NMOSD may be associated with a variety of different types of autoimmune diseases. Therefore, systemic or laboratory signs which are not typical for NMOSD should be properly investigated to exclude other associated comorbidities. These comorbidities may affect the treatment strategy and may improve the patients' care and management.
Coexisting systemic and organ-specific autoimmunity in MOG-IgG1-associated disorders versus AQP4-IgG+ NMOSD.
Kunchok Amy,Flanagan Eoin P,Snyder Melissa,Saadeh Ruba,Chen John J,Weinshenker Brian G,McKeon Andrew,Pittock Sean J
Multiple sclerosis (Houndmills, Basingstoke, England)
Aquaporin-4 (AQP4) neuromyelitis optica spectrum disorder (NMOSD) has been demonstrated to be associated with non-organ and organ-specific autoantibodies (antinuclear antibody, extractable nuclear antibody, double-stranded DNA, muscle acetylcholine receptor antibody) and systemic autoimmune diseases. In this study, we evaluated whether a similar association with non-organ and organ-specifc autoantibodies occurs in patients with MOG-IgG1-associated disorders. We determined that MOG-IgG1 was not strongly associated with these organ and non-organ-specific autoantibodies. Systemic lupus erythematous (SLE) was significantly associated with AQP4-IgG+ NMOSD and not with MOGAD ( = 0.037). These findings suggest differences in co-existing systemic and organ-specific autoimmunity between MOGAD and AQP4-IgG+ NMOSD.
MOG-IgG-associated disorder and systemic lupus erythematosus disease: Systematic review.
Caroline Breis Leticia,Antônio Machado Schlindwein Marco,Pastor Bandeira Isabelle,Machiavelli Fontana Thaíse,Fiuza Parolin Laura,Weingrill Pedro,Kleinpaul Vieira Rodrigo Gonçalves,Vinícius Magno Gonçalves Marcus
INTRODUCTION:Myelin oligodendrocyte glycoprotein (MOG) is a nervous system protein expressed by oligodendrocytes to constitute the myelin sheath. Autoantibodies against MOG have been widely described in neurological and autoimmune diseases such as MOG-IgG-associated disorder (MOGAD).Although underlying mechanisms have not yet been understood, an overlap of MOGAD and Systemic Lupus Erythematosus (SLE) has been shown in the literature. OBJECTIVES:The aim of this systematic review was to assess the possible correlations between MOGAD and SLE based on reported features found in the literature that support the association of the two. METHODS:A keyword-based literature search was conducted, applying a ten-year filter and using the following key-words: "MOG autoantibody-associated disease and Systemic Lupus Erythematosus"; "MOG and Systemic Lupus Erythematosus" "Anti-MOG and Lupus"; "MOG and SLE"; "MOG and LUPUS" on MEDLINE/PUBMED, ScienceDirect, SciELO, LILACS and Cochrane; and "MOG antibody-associated disease and SLE" on Google Scholar. RESULTS:Eleven publications reporting on the MOGAD and SLE correlation were included in qualitative synthesis: animal experiment (1), cross-sectional (3), prospective (2), retrospective (1), non-systematic review (3), and case report (1) studies. CONCLUSION:Not much is known about the connection between MOG-IgG-associated disorder and SLE. Unfortunately, only observational studies have been conducted in humans so far, providing us with limited data. While MOGAD features have been reported to develop in SLE patients, this is not an universal finding. In fact, many different issues impair these results, making it difficult to match the findings of different studies.
MOG-IgG myelitis coexisting with systemic lupus erythematosus in the post-partum setting.
Bilodeau Philippe A,Kumar Vinayak,Rodriguez Andrew E,Li Clarence T,Sanchez-Alvarez Catalina,Thanarajasingam Uma,Zalewski Nicholas L,Flanagan Eoin P
Multiple sclerosis (Houndmills, Basingstoke, England)
BACKGROUND:Longitudinally extensive transverse myelitis (LETM) accompanying systemic lupus erythematosus (SLE) is often due to coexisting aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder but has not been associated with myelin oligodendrocyte glycoprotein-IgG (MOG-IgG). OBJECTIVE AND METHODS:Case report at an academic medical center. RESULTS:A 32-year-old woman developed severe transverse myelitis (paraplegia) shortly after SLE onset in the post-partum period. Magnetic resonance imaging (MRI) revealed an LETM, cerebrospinal fluid showed marked inflammation, and testing for infections was negative. Serum live-cell-based assay for MOG-IgG was positive but aquaporin-4-IgG was negative. CONCLUSION:In patients with SLE and LETM, MOG-IgG testing should be considered, in addition to AQP4-IgG.
The Clinical Characteristics of Primary Sjogren's Syndrome With Neuromyelitis Optica Spectrum Disorder in China: A STROBE-Compliant Article.
Qiao Lin,Wang Qian,Fei Yunyun,Zhang Wen,Xu Yan,Zhang Yao,Zhao Yan,Zeng Xiaofeng,Zhang Fengchun
The aim of the present study was to analyze the clinical characteristics of primary Sjogren's syndrome (pSS) with neuromyelitis optica spectrum disorder (NMOSD). We retrospectively reviewed the medical records of 616 patients who were admitted to the Peking Union Medical College Hospital from 1985 to 2013. Of these patients, 43 developed NMOSD. The median duration of symptoms was 60 months and 72% of the patients experienced neurological complications onset in the pSS with NMOSD group. Twenty-one out of 43 patients had neuromyelitis optica (NMO), and 22 exhibited a limited form of NMO. Serum anti-aquaporin-4 (AQP4) antibody positivity was detected in 89.3% of the patients. A total of 60.5% of the patients (26 patients) complained of dry mouth, 72.1% were positive for objective xerostomia, 53.5% complained of dry eyes, and 74.4% had a positive ocular test. Biopsy of the minor salivary glands was performed in 33 patients, 28 of whom (84.8%) had a lymphocytic focus score of ≥1. Anti-Ro/SSA or anti-La/SSB antibodies were detected in 41 patients (95.3%). Compared with the pSS patients without NMOSD, the incidences of xerophthalmia, xerostomia, arthritis, interstitial lung disease, and renal tubular acidosis were significantly lower in the patients with NMOSD. NMOSD is a neurologic complication of pSS. The presence of anti-AQP4 antibody may be a predictor for pSS patients with NMOSD. Neurological manifestations are prominent in these patients. In clinical scenarios involving pSS or NMOSD, rheumatologists and neurologists should be aware of this association and perform the appropriate tests.
Clinical features of transverse myelitis associated with systemic lupus erythematosus.
Zhang S,Wang Z,Zhao J,Wu D I,Li J,Wang Q,Su J,Xu D,Wang Y,Li M,Zeng X
OBJECTIVE:This study aimed to identify the clinical characteristics and prognostic factors of systemic lupus erythematosus with transverse myelitis (SLE-TM) in a relatively large patient series. METHODS:This retrospective study considered 45 SLE-TM individuals treated as inpatients and outpatients at Peking Union Medical College Hospital between 1993 and 2018. SLE-TM patients were compared with 180 controls, and SLE-TM patients with neuromyelitis optica spectrum disorder (NMOSD) were compared to those without NMOSD. RESULTS:Compared to controls, the SLE-TM group frequently had a fever and had a significantly higher positive rate of anticardiolipin and lupus anticoagulant. Among the 45 patients, 22 met the NMOSD criteria. Compared to non-NMOSD patients, NMOSD patients had a lower incidence of rash ( = 0.023), serositis ( = 0.042) and renal disorder ( = 0.073); a lower prevalence of decreased complement ( = 0.083); and lower rates of positive anti-dsDNA ( = 0.074) and anti-Sm ( = 0.042). Among 22 SLE-TM patients with NMOSD, 18 underwent aquaporin 4 antibody testing, with 11 showing positive results. Out of the 45 patients, 39 were given methylprednisolone pulse treatment. After treatment, 32 patients had lower-limb muscle strength recovery (recovered group), whereas 13 had no change and persistent severe neurological deficits (non-recovered group). Compared to the recovered group, the non-recovered group were younger ( = 0.002), had a higher likelihood of having a fever ( = 0.020), initial severe myelitis ( < 0.001), long spinal segment involvement ( = 0.017) and higher C-reactive protein levels ( = 0.020). Methylprednisolone pulse given within two weeks of onset was more frequent in the recovered group than in the non-recovered group ( = 0.082). CONCLUSIONS:Disease characteristics differed between SLE-TM patients with and without NMOSD. SLE and NMOSD tended to be co-morbidities. Initial severe neurological impairment, extensive spinal cord lesions, hyper-inflammation and delayed steroid impulse treatment could be predictors of poor outcome for SLE-TM.
[Comorbidity of neuromyelitis optica spectrum disorder and systemic lupus erythematosus].
Krasnov V S,Makshakov G S,Kalinin I V,Laskova K K,Shumilina M V,Evdoshenko E P,Totolyan N A
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova
The comorbidity of neuromyelitis optica spectrum disorder (NMOSD) and systemic lupus erythematosus (SLE) is a poorly studied problem. The issues of the pathogenetic relationship between these diseases, timely diagnosis of their co-existence in one patient, disease course and therapeutic approaches are the most relevant. The authors summarize current views on the state of the problem and analyze three clinical cases of NMOSD and SLE comorbidity including the diagnostic issues and therapeutic approaches.
Age-Related Clinical Presentation of MOG-IgG Seropositivity in Israel.
Brill Livnat,Ganelin-Cohen Esther,Dabby Ron,Rabinowicz Shira,Zohar-Dayan Efrat,Rein Netaniel,Aloni Eyal,Karmon Yuval,Vaknin-Dembinsky Adi
Frontiers in neurology
Myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders (MOGAD) have been recognized over the past 10 years as distinct inflammatory, demyelinating diseases of the central nervous system (CNS). Antibodies against MOG are found mostly in patients with optic neuritis (ON), acute disseminated encephalomyelitis (ADEM), and aquaporin-4 antibody (AQP4-abs)-seronegative neuromyelitis optica spectrum disorders (NMOSD). However, data on the disease course and disability outcomes of these patients are scarce. To describe clinical and paraclinical features associated with MOG antibodies (abs) in a cohort of patients in Israel, and to assess baseline prognostic features of MOG-ab-associated diseases after a first acute demyelinating event. MOG-abs were identified in serum using a cell-based assay, and clinical data were collected from the patients' medical records. Of 683 patients with demyelinating diseases tested for MOG-abs, 53 were positive (7.7%), with ON the most common presenting phenotype (68%). The age range of MOG-abs seropositive patients was 1-66 years, with increased prevalence in children (19% compared to 6.7% in adults) ( < 0.01). The highest prevalence of seropositivity was observed in children aged younger than 10 years (25.5%), followed by those aged 31-40 years (16.6%). MOGAD are distinct autoimmune diseases that occurs at all stages of life with a significantly higher prevalence in children; the main clinical presenting phenotype in the entire cohort is ON and young children most often presented with ON or ADEM. Our data highlight the need for repeated evaluation of MOG-abs in patients with acquired CNS demyelinating disorders, especially in children under 10 and adults between 31 and 40 years of age.
Treatment Approaches for MOG-Ab-Associated Demyelination in Children.
Hacohen Yael,Banwell Brenda
Current treatment options in neurology
PURPOSE OF REVIEW:The purpose of this review is to summarize current understanding regarding the treatment of myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated demyelination in children. Emphasis is placed on the unique obstacles we face when predicting the risk of relapse and the important implications of such challenges when planning treatment protocols. RECENT FINDINGS:MOG-Abs are consistently identified in a range of acquired demyelinating syndromes (ADS) in adults and children with a clinical phenotype distinct of MS and AQP4-Ab neuromyelitis optica spectrum disorder. Although initially thought to be associated with a benign disease, recent reports of children who are treatment-resistant and developed progressive disability over time raise important questions about how children with relapsing MOG-Ab disease should be managed. MOG-Abs are common in children with ADS with both monophasic and relapsing disease courses. Treatment of patients with MOG-Ab-associated demyelination includes management of acute relapses and chronic immunotherapy for those with relapsing disease. Emerging consensus supports distinction of treatment strategies from those typically used for relapsing remitting MS, and several groups debate whether to follow treatment protocols akin to those for AQP4-Ab NMOSD. A key challenge remains predicting the severity of the disease at onset. Collaborative international consensus to derive shared clinical evaluative platforms standardized biological and neuroimaging protocols which can be used clinically, and partnered research programs are required to advance personalized treatment for children with MOG-Ab-associated demyelination.
Clinical experience of plasmapheresis for neuromyelitis optica patients in Mexico.
Gómez-Figueroa Enrique,Alvarado-Bolaños Alonso,García-Estrada Christian,Zabala-Ángeles Indhira,Sánchez-Rosales Nayeli,Bribiesca-Contreras Elisa,García-Alvarez Gabriela,Montes-Pérez Yessica,Ramos-Vega Erasmo,Casallas-Vanegas Adriana,Carrillo-Loza Karina,Corona-Vázquez Teresita,Rivas-Alonso Verónica,Flores-Rivera José
Multiple sclerosis and related disorders
BACKGROUND:Neuromyelitis optica spectrum disorders (NMOSDs) are a group of chronic immune-mediated demyelinating diseases of the central nervous system. Their pathophysiology dependent on humoral mediated responses caused by autoreactive IgG antibodies against aquaporin-4 water channels (AQP4-IgG) or myelin oligodendrocyte glycoprotein (MOG-IgG). Plasma exchange (PLEX) has proved to be a beneficial therapy in patients with severe relapses. We present the largest series of Latin American patients treated with PLEX for acute NMOSDs relapses. METHODS:A retrospective study was conducted. Selection included patients diagnosed with NMOSDs who received PLEX between 2010-2019, irrespective of their AQP4-IgG serostatus. All patients received 5 grams of IV methylprednisolone. PLEX therapy could be initiated simultaneously or after IV steroids. Baseline and post-PLEX therapy Expanded Disability Status Scale (EDSS) was measured to identify acute response to therapy. Comparison between responders and non-responders was also conducted. Subgroup analysis stratified response by serostatus, type of clinical relapse and time to PLEX. RESULTS:A total of 89 patients were included. Mean age at onset was 38 ± 12.97 years. 49 (55.1%) patients were AQP4-IgG seropositive. Most patients had unilateral optic neuritis (34.8%) or longitudinally extensive transverse myelitis (33.7%). Mean time from onset to PLEX initiation was 20.9 ± 18.1 days. Response rate was 39.3% and mean decline in EDSS was 0.7 ± 0.9 (p <0.001). Decline in EDSS and response rate were independent of serostatus, type of clinical relapse or time to PLEX initiation. CONCLUSION:PLEX appears to be an effective therapy for NMOSDs relapses even in limited resources setting where treatment initiation may be delayed. The benefit seems to be independent of the type of clinical relapse and AQP4 IgG serostatus.
Comparison of Clinical Outcomes of Transverse Myelitis Among Adults With Myelin Oligodendrocyte Glycoprotein Antibody vs Aquaporin-4 Antibody Disease.
Mariano Romina,Messina Silvia,Kumar Kurun,Kuker Wilhelm,Leite Maria Isabel,Palace Jacqueline
JAMA network open
Importance:Recognizing the differences between transverse myelitis (TM) associated with myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) disease vs aquaporin-4 (AQP4)-Ab disease and prognosticating patients within each group may be an important factor for better clinical treatment for these respective patients. Objectives:To compare the clinical and radiological findings of the first TM episode in patients with MOG-Ab disease vs patients with AQP4-Ab disease and to assess factors associated with worse outcomes and relapse risk. Design, Setting, and Participants:This retrospective cross-sectional study used data collected from the Oxford Neuromyelitis Optica Service database, a national service that serves the south of England, including detailed clinical data, and high-quality imaging from within 4 weeks of the first TM episode from patients with MOG-Ab disease or AQP4-Ab disease and a confirmed history of TM from April 2018 to January 2019. Data analyses were conducted from February 2019 to April 2019. Main Outcomes and Measures:Onset features of each condition measured using the Expanded Disability Status Scale (EDSS) score, time to an EDSS score of 6, time to relapse, and residual sphincter dysfunction at least 6 months after the first TM episode and at last follow-up. Results:The total cohort included 115 adult patients, including 46 patients with MOG-Ab disease and 69 patients with AQP4-Ab disease. Patients with AQP4-Ab disease, compared with patients with MOG-Ab disease, tended to be older at onset of disease (mean [SD] age, 48.5 [14.9] years vs 33.7 [1.2] years) and female (57 [83%] women vs 24 [52%] women). Transverse myelitis occurred at onset of disease for 32 patients (70%) with MOG-Ab disease and 57 patients (78%) with AQP4-Ab disease. Onset severity did not differ between groups. An acute disseminated encephalomyelitis-like presentation occurred at the time of the TM in 4 patients (9%) with MOG-Ab disease but no patients with AQP4-Ab disease. Compared with patients with AQP4-Ab disease, patients with MOG-Ab disease were more likely to have short cord lesions (22 patients [48%] vs 10 patients [15%]; P < .001) and multiple cord lesions (18 patients [39%] vs 7 patients [10%]; P < .001). Approximately 50% of patients with MOG-Ab disease had only short cord lesions when the TM occurred as a relapse. Median (range) recovery EDSS score was lower in patients with MOG-Ab disease than patients with AQP4-Ab disease (1.8 [1.0-8.0] vs 3.0 [1.0-8.0]). Persistent bladder dysfunction associated with an increased prevalence of conus lesions occurred more frequently in patients with MOG-Ab disease than in patients with AQP4-Ab disease (27 patients [59%] vs 33 patients [48%]). Long-term catheter requirement was roughly equal between groups (9 patients [20%] vs 16 patients [23%]). Relapses after TM occurred in 17 patients with MOG-Ab disease (37%) and 36 patients with AQP4-Ab disease (52%). Concomitant brainstem lesions in patients with MOG-Ab disease were associated with a higher mean (SD) EDSS score at recovery (3.5 [2.3] vs 1.4 [0.9]; P < .001). In patients with AQP4-Ab disease, those younger than 50 years were more likely to relapse (27 of 36 patients aged <50 years [75%] vs 9 of 33 patients aged ≥50 years [27%]; P < .001) and those 50 years and older were more likely to reach an EDSS score of 6 (19 of 33 patients aged ≥50 years [58%] vs 11 of 36 patients aged <50 years [31%]; P = .03). Conclusions and Relevance:This study found that in patients who experienced a TM episode, short and multiple lesions at onset were more common in those with MOG-Ab disease than among those with AQP4-Ab disease. The presence of a brainstem lesion at the time of a TM episode in patients with MOG-Ab disease was associated with a worse recovery. In patients with AQP4-Ab disease, those 50 years and older at disease onset had more disability, and those younger than 50 years at disease onset had more relapses.
Comparison of clinical characteristics and prognoses in patients with different AQP4-Ab and MOG-Ab serostatus with neuromyelitis optica spectrum disorders.
Du Qin,Shi Ziyan,Chen Hongxi,Zhang Ying,Wang Jiancheng,Qiu Yuhan,Zhao Zhengyang,Zhang Qin,Zhou Hongyu
Journal of neuroimmunology
BACKGROUND:At present, patients positive for aquaporin-4 antibody (AQP4-Ab) or myelin oligodendrocyte glycoprotein antibody (MOG-Ab) are diagnosed as neuromyelitis optica spectrum disorder (NMOSD) and MOG-Ab-associated diseases, respectively. However, some patients who meet the diagnostic criteria for NMOSD and show demyelination of the central nervous system cannot be clearly classified. METHODS:We performed a prospective cohort study to evaluate the clinical characteristics and prognoses of double-seronegative patients with NMOSD. RESULTS:A total of 594 patients were included in the cohort, including 26 patients with MOG-Ab, 517 with AQP4-Ab, and 51 with double seronegativity. Compared to AQP4-Ab-positive patients, double-seronegative patients experienced less severe clinical attacks (51.0% vs. 78.1%; P < 0.01), either visual (23.5% vs. 42.6%; P = 0.024) or motor attacks (39.2% vs. 59.8%; P = 0.015), and had a better median Expand Disability Status Scale (EDSS) score at the last follow-up (2.0 vs. 3.0; P = 0.012) and a lower proportion of disability (11.8% vs. 30.9%; P = 0.015). Furthermore, lower risks of visual and motor disability were also observed by Kaplan-Meier analyses (P = 0.031 and 0.038, respectively). Both the MOG-Ab and double-seronegative groups had lower frequencies of severe clinical attacks, especially motor attacks, better EDSS scores at the last visit, and a lower proportion of disability than was found in the AQP4-Ab group (all P values and corrected P values <0.05). CONCLUSIONS:In patients who met the diagnostic criteria for NMOSD, compared with AQP4-Ab-seropositive patients, double-seronegative and MOG-Ab-seropositive patients had less severe clinical attacks and better prognoses, including lower EDSS scores and a lower proportion of disability.
Differences in symptoms of depression between females and males with relapsing-remitting multiple sclerosis.
Mayo Chantel D,Lacey Colleen,Gawryluk Jodie R,
Multiple sclerosis and related disorders
INTRODUCTION:Depressive symptoms are experienced by up to 50% of individuals diagnosed with Multiple Sclerosis (MS). Furthermore, depressive symptoms are sometimes experienced differently for females and males in the general population, but it is unclear if this is true for people with Relapsing-Remitting MS (RRMS). The current study aimed to investigate whether there are differences between females and males with RRMS in overall depression scores as well as the types of depressive symptoms reported (somatic or cognitive). METHOD:Demographic and Beck Depression Inventory, 2 edition (BDI-II) raw scores for females and males with RRMS were downloaded with permission from the Multiple Sclerosis Outcome Assessments Consortium (MSOAC) Placebo database. A total of 494 individuals (n=354 females) with RRMS were included in analyses. Non-parametric Wilcoxon rank-sum tests were used to compare BDI-II Total Scores, Somatic Scores, and Cognitive Scores between females and males with RRMS. RESULTS:Females reported significantly greater overall symptoms of depression compared to males. Furthermore, females endorsed significantly greater somatic symptoms than males. There were no significant differences in females' reports of cognitive symptoms compared to males. CONCLUSIONS:Depressive symptoms in RRMS are experienced differently for females and males. Females with RRMS report higher levels of overall depression and somatic depressive symptoms compared to males with RRMS; this knowledge may help inform best strategies for treatment planning. Future studies should investigate depressive symptoms in females and males with progressive forms of MS, and track symptom changes longitudinally.
In vitro and in vivo models of acute alcohol exposure.
Dolganiuc Angela,Szabo Gyongyi
World journal of gastroenterology
Alcohol abuse is a global problem due to the financial burden on society and the healthcare system. While the harmful health effects of chronic alcohol abuse are well established, more recent data suggest that acute alcohol consumption also affects human wellbeing. Thus, there is a need for research models in order to fully understand the effect of acute alcohol abuse on different body systems and organs. The present manuscript summarizes the interdisciplinary advantages and disadvantages of currently available human and non-human models of acute alcohol abuse, and identifies their suitability for biomedical research.
Neuroscience of alcoholism: molecular and cellular mechanisms.
Moonat Sachin,Starkman Bela G,Sakharkar Amul,Pandey Subhash C
Cellular and molecular life sciences : CMLS
Alcohol use and abuse appear to be related to neuroadaptive changes at functional, neurochemical, and structural levels. Acute and chronic ethanol exposure have been shown to modulate function of the activity-dependent gene transcription factor, cAMP-responsive element binding (CREB) protein in the brain, which may be associated with the development of alcoholism. Study of the downstream effectors of CREB have identified several important CREB-related genes, such as neuropeptide Y, brain-derived neurotrophic factor, activity-regulated cytoskeleton-associated protein, and corticotrophin-releasing factor, that may play a crucial role in the behavioral effects of ethanol and molecular changes in the specific neurocircuitry that underlie both alcohol addiction and a genetic predisposition to alcoholism. Brain chromatin remodeling due to histone covalent modifications may also be involved in mediating the behavioral effects and neuroadaptive changes that occur during ethanol exposure. This review outlines progressive neuroscience research into molecular and epigenetic mechanisms of alcoholism.
Molecular basis of alcoholism.
Most Dana,Ferguson Laura,Harris R Adron
Handbook of clinical neurology
Acute alcohol intoxication causes cellular changes in the brain that last for hours, while chronic alcohol use induces widespread neuroadaptations in the nervous system that can last a lifetime. Chronic alcohol use and the progression into dependence involve the remodeling of synapses caused by changes in gene expression produced by alcohol. The progression of alcohol use, abuse, and dependence can be divided into stages, which include intoxication, withdrawal, and craving. Each stage is associated with specific changes in gene expression, cellular function, brain circuits, and ultimately behavior. What are the molecular mechanisms underlying the transition from recreational use (acute) to dependence (chronic)? What cellular adaptations result in drug memory retention, leading to the persistence of addictive behaviors, even after prolonged drug abstinence? Research into the neurobiology of alcoholism aims to answer these questions. This chapter will describe the molecular adaptations caused by alcohol use and dependence, and will outline key neurochemical participants in alcoholism at the molecular level, which are also potential targets for therapy.
Alcohol and the Brain: Neuronal Molecular Targets, Synapses, and Circuits.
Abrahao Karina P,Salinas Armando G,Lovinger David M
Ethanol is one of the most commonly abused drugs. Although environmental and genetic factors contribute to the etiology of alcohol use disorders, it is ethanol's actions in the brain that explain (1) acute ethanol-related behavioral changes, such as stimulant followed by depressant effects, and (2) chronic changes in behavior, including escalated use, tolerance, compulsive seeking, and dependence. Our knowledge of ethanol use and abuse thus relies on understanding its effects on the brain. Scientists have employed both bottom-up and top-down approaches, building from molecular targets to behavioral analyses and vice versa, respectively. This review highlights current progress in the field, focusing on recent and emerging molecular, cellular, and circuit effects of the drug that impact ethanol-related behaviors. The focus of the field is now on pinpointing which molecular effects in specific neurons within a brain region contribute to behavioral changes across the course of acute and chronic ethanol exposure.
Effects of the Acute and Chronic Ethanol Intoxication on Acetate Metabolism and Kinetics in the Rat Brain.
Hsieh Ya-Ju,Wu Liang-Chih,Ke Chien-Chih,Chang Chi-Wei,Kuo Jung-Wen,Huang Wen-Sheng,Chen Fu-Du,Yang Bang-Hung,Tai Hsiao-Ting,Chen Sharon Chia-Ju,Liu Ren-Shyan
Alcoholism, clinical and experimental research
BACKGROUND:Ethanol (EtOH) intoxication inhibits glucose transport and decreases overall brain glucose metabolism; however, humans with long-term EtOH consumption were found to have a significant increase in [1- C]-acetate uptake in the brain. The relationship between the cause and effect of [1- C]-acetate kinetics and acute/chronic EtOH intoxication, however, is still unclear. METHODS:[1- C]-acetate positron emission tomography (PET) with dynamic measurement of K and k rate constants was used to investigate the changes in acetate metabolism in different brain regions of rats with acute or chronic EtOH intoxication. RESULTS:PET imaging demonstrated decreased [1- C]-acetate uptake in rat brain with acute EtOH intoxication, but this increased with chronic EtOH intoxication. Tracer uptake rate constant K and clearance rate constant k were decreased in acutely intoxicated rats. No significant change was noted in K and k in chronic EtOH intoxication, although 6 of 7 brain regions showed slightly higher k than baseline. These results indicate that acute EtOH intoxication accelerated acetate transport and metabolism in the rat brain, whereas chronic EtOH intoxication status showed no significant effect. CONCLUSIONS:In vivo PET study confirmed the modulatory role of EtOH, administered acutely or chronically, in [1- C]-acetate kinetics and metabolism in the rat brain. Acute EtOH intoxication may inhibit the transport and metabolism of acetate in the brain, whereas chronic EtOH exposure may lead to the adaptation of the rat brain to EtOH in acetate utilization. [1- C]-acetate PET imaging is a feasible approach to study the effect of EtOH on acetate metabolism in rat brain.
Changes in cerebral [F]-FDG uptake induced by acute alcohol administration in a rat model of alcoholism.
Gispert Juan D,Figueiras Francisca P,Vengeliene Valentina,Herance José R,Rojas Santiago,Spanagel Rainer
Behavioural brain research
Several [F]-FDG positron emission tomography (PET) studies in alcoholics have consistently reported decreases in overall brain glucose metabolism at rest and following acute alcohol administration. However, changes in cerebral glucose utilization associated with the transition to addiction are not well understood and require longitudinal translational imaging studies in animal models of alcoholism. Here, we studied brain glucose uptake in alcohol drinking rats in order to provide convergent evidence to what has previously been reported in human studies. Brain glucose metabolism was measured by [F]-FDG microPET imaging in different male Wistar rat groups: short-term drinking (three months), long-term drinking (twelve months) and alcohol-naïve. Global and regional cerebral glucose uptake was measured at rest and following acute alcohol administration. We showed that alcohol significantly reduced the whole-brain glucose metabolism. This effect was most pronounced in the parietal cortex and cerebellum. Alcohol-induced decreases in brain [F]-FDG uptake was most apparent in alcohol-naïve rats, less intense in short-term drinkers and absent in long-term drinkers. The latter finding indicates the occurrence of tolerance to the intoxicating effects of alcohol in long-term drinking individuals. In contrast, some regions, like the ventral striatum and entorhinal cortex, showed enhanced metabolic activity, an effect that did not undergo tolerance during long-term alcohol consumption. Our findings are comparable to those described in human studies using the same methodology. We conclude that [F]-FDG PET studies in rat models of alcoholism provide good translation and can be used for future longitudinal studies investigating alterations in brain function during different stages of the addiction cycle.
[Relationship between the Expression of α-syn and Neuronal Apoptosis in Brain Cortex of Acute Alcoholism Rats].
Li F,Zhang Y,Ma S L
Fa yi xue za zhi
OBJECTIVES:To observe the changes of expression of α-synuclein （α-syn） and neuronal apoptosis in brain cortex of acute alcoholism rats and to explore the mechanism of the damage caused by ethanol to the neurons. METHODS:The model of acute alcoholism rat was established by 50% alcohol gavage. The α-syn and caspase-3 were detected by immunohistochemical staining and imaging analysis at 1 h, 3 h, 6 h and 12 h after acute alcoholism. The number of positive cell and mean of optical density were detected and the trend change was analyzed. The variance analysis and -test were also performed. RESULTS:The number of α-syn positive cell and average optical density in brain cortex of acute alcoholism rat increased significantly and peaked at 6 hour with a following slight decrease at 12 h, but still higher than the groups at 1 h and 3 h. Within 12 hours after poisoning, the number of caspase-3 positive cell and average optical density in brain cortex of rats gradually increased. CONCLUSIONS:The abnormal aggregation of α-syn caused by brain edema and hypoxia may participate the early stage of neuronal apoptosis in brain cortex after acute alcoholism.
Assessment of Renal Deterioration and Associated Risk Factors in Patients With Multiple Sclerosis.
Shakir Nabeel A,Satyanarayan Arthi,Eastman Jessica,Greenberg Benjamin M,Lemack Gary E
OBJECTIVE:To evaluate predictors of renal deterioration (RD) in patients with multiple sclerosis (MS) at a tertiary referral center. METHODS:We reviewed adult patients with MS presenting for evaluation of lower urinary tract symptoms, with baseline urodynamic study (UDS) and either serum creatinine (SCr) or renal ultrasound, from a prospectively maintained database, and excluded patients with abnormal renal function. RD was defined as doubled SCr, new hydronephrosis, or renal atrophy on follow-up ultrasound. Demographic and UDS parameters were evaluated in multivariable models of RD. RESULTS:From 1999 to 2016, 660 patients were evaluated, and 355 met criteria with median follow-up of 79 months. SCr doubled in 8 patients, 4 had decline by renal ultrasound, and 1 by both (3%). Overall, 46 patients met less strict criteria of decrease in estimated glomerular filtration rate by ≥30%. Using the less rigid criterion, detrusor overactivity (DO) remained associated with RD on multivariable analysis. Eleven of 355 patients had RD by either imaging or doubled Cr, with which only history of diabetes mellitus and nephrolithiasis were associated. CONCLUSION:By strict criteria, the rate of RD in patients with neurogenic bladder due to MS was low (3%) at intermediate-term follow-up and was not associated with UDS parameters. Using more liberal criteria, DO was associated with deterioration, suggesting that study of the impact of more aggressive control of DO in this population may be warranted.
Psychiatric comorbidity in multiple sclerosis.
Panda S P,Das R C,Srivastava Kalpana,Ratnam Ashutosh,Sharma Neha
Neurologia i neurochirurgia polska
AIM:To study the prevalence of psychiatric comorbidities in patients of multiple sclerosis and their association to the degree of disability. METHOD:Psychiatric symptoms were assessed in 90 patients of multiple sclerosis using GHQ-12, MMSE, HADS, Beck Depression Inventory and AUDIT. Neurological disability was assessed using Expanded Disability Status Scale. Correlations were determined between EDSS scores and psychiatric scale scores. RESULT:61% of patients had significant psychological distress. Depression was most common (38.8%) which was followed by anxiety symptoms (27.8%). Cognitive functioning was relatively intact in patients with mild to moderate neurological disability. Alcohol abuse was mostly restricted to male gender. CONCLUSION:Psychiatric illness is highly prevalent in patients of multiple sclerosis leading to poor quality of life and significant distress. Psychiatric disability was higher in patients who had greater deterioration in neurological function. All cases of MS should be assessed for psychiatric morbidities as can be alleviated by appropriate intervention.
Long-term prognosis of symptomatic isolated middle cerebral artery disease in Korean stroke patients.
Oh Mi Sun,Yu Kyung-Ho,Chu Min-Kyung,Ma Hyeo-Il,Kim Yun Joong,Kim Joo Yong,Lee Byung-Chul
BACKGROUND:This study aimed to investigate the long-term mortality and recurrence rate of stroke in first-time stroke patients with symptomatic isolated middle cerebral artery disease (MCAD) under medical management. METHODS:We identified 141 first ever stroke patients (mean age, 64.4 ± 12.5 years; 53% male) with symptomatic isolated MCAD. MCAD was defined as significant stenosis of more than 50% or occlusion of the MCA as revealed by MR angiography. The median follow-up was 27.7 months. We determined a cumulative rate of stroke recurrence and mortality by Kaplan-Meier survival analyses and sought predictors using the Cox proportional hazard model. RESULTS:The cumulative composite outcome rate (stroke recurrence or any-cause death) was 14%, 19%, 22%, and 28% at years 1, 2, 3, and 5, respectively. The annual recurrence rate of stroke was 4.1%. The presence of diabetes mellitus was the only significant independent predictor of stroke recurrence or any cause of death in multivariate analyses of Cox proportional hazard model adjusted for any plausible potential confounding factors. CONCLUSIONS:We estimated the long-term prognosis of stroke patients with isolated symptomatic MCAD under current medical management in Korea. Diabetes mellitus was found to be a significant predictor for stroke recurrence and mortality.
Prognostic factors and therapeutic outcome of isolated symptomatic middle cerebral artery stenosis.
Tsai N-W,Chang H-W,Chang W-N,Huang C-R,Lin T-K,Chen S-D,Lui C-C,Wang K-W,Cheng B-C,Hung P-L,Chang C-S,Lu C-H
European journal of neurology
To analyze the prognostic factors and therapeutic outcome of adult patients with isolated symptomatic stenosis of the middle cerebral artery (MCA). Forty-nine patients were retrospectively verified with isolated symptomatic stenosis of the MCA through both magnetic resonance angiogram and transcranial color-coded duplex sonography. Therapeutic outcome at 1 year or more was determined using a modified Barthel index (BI). For the purpose of analysis, the patients were divided into two groups: a good outcome group (BI > or = 12) and a poor outcome group (BI < 12 or recurrent stroke). The association between different therapeutic regimens and the percent free of recurrent stroke after the first event of cerebral infarction was assessed with Kaplan-Meier plots compared by a log-rank test. These patients accounted for 2.8% of all patients with the first event of cerebral infarction during the same period. At follow-up of 1 year or more, 63% had good outcomes whilst the other 37% had poor outcomes. Overall, 26.5% suffered from recurrent strokes during the follow-up period. According to the statistical analysis, the stepwise logistic regression revealed that only the National Institutes of Health Stroke Scale (NIHSS) at the time of admission was independently associated with a poor outcome. Furthermore, Kaplan-Meier analysis showed a significantly higher percentage of patients free of recurrent stroke events amongst those who were treated with warfarin. The NIHSS at the time of admission was a predictor of outcome amongst our patients, and stenosis of the MCA implies the danger of recurrent cerebral events. Our study also demonstrates the efficacy of oral anticoagulants in the secondary prevention in this specific group of patients. Therefore, we look forward to more prospective multicenter investigations in evaluating the efficiency of therapy in the future.
Inclusion body myositis and sarcoid myopathy: coincidental occurrence or associated diseases.
Sanmaneechai Oranee,Swenson Andrea,Gerke Alicia K,Moore Steven A,Shy Michael E
Neuromuscular disorders : NMD
Inclusion body myositis (IBM) is a slowly progressive inflammatory myopathy characterized by selective weakness of finger flexors and quadriceps muscles commonly refractory to treatment. Another chronic inflammatory disorder, sarcoidosis, commonly involves muscle. The comorbidity of inclusion body myositis and sarcoid myopathy is rare. We describe clinical and muscle biopsy findings of a patient with sarcoidosis and inclusion body myositis. A 66-year-old man presented with a 6-year history of progressive, asymmetrical and selective weakness of the quadriceps, biceps and finger flexor muscles; he had a remote history of pulmonary sarcoidosis. A quadriceps muscle biopsy revealed a chronic inflammatory myopathy with ubiquitinated inclusion bodies, rimmed vacuoles, expression of major histocompatibility complex class I, numerous COX-negative fibers and TDP-43 cytoplasmic aggregates (features of IBM) and multiple non-necrotizing granulomata (feature of sarcoidosis). Clinical and histopathologic features of the current illness suggested the patient had sarcoidosis with inclusion body myositis overlap. This patient may represent the coincidental occurrence of both idiopathic inflammatory disorders. Alternatively, sarcoidoisis may promote the development of inclusion body myositis by a similar immune-mediated pathophysiologic process.
Distal muscle involvement in granulomatous myositis can mimic inclusion body myositis.
Larue Sandrine,Maisonobe Thierry,Benveniste Olivier,Chapelon-Abric Catherine,Lidove Olivier,Papo Thomas,Eymard Bruno,Dubourg Odile
Journal of neurology, neurosurgery, and psychiatry
The authors report on four patients aged over 50 with chronic myopathy suggestive of sporadic inclusion body myositis. They present progressive and selective weakness of the quadriceps femoris muscles. Asymmetrical and selective atrophy of the forearm muscles were noted in all, with more severe involvement of the flexors than the extensors. Biopsy revealed granulomatous myositis. Histological features of sporadic inclusion body myositis were lacking. Evidence for systemic sarcoidosis was found in one patient. Corticosteroid treatment was associated with a partial but significant improvement in two patients. Granulomatous myositis may mimic inclusion body myositis and may be steroid-responsive.
Sporadic inclusion body myositis misdiagnosed as idiopathic granulomatous myositis.
Lavian Monica,Goyal Namita,Mozaffar Tahseen
Neuromuscular disorders : NMD
We present a case of a 65-year-old woman who was previously diagnosed with idiopathic granulomatous myositis and treated with immunosuppressive therapy for the next 10 years before a clinical diagnosis of inclusion body myositis was made. A review of the previously performed muscle biopsy showed most of the cardinal myopathologic features of sporadic inclusion body myositis, in addition to the granuloma. Her clinical course was strongly suggestive of inclusion body myositis with selective asymmetric weakness of forearm flexor muscles and quadriceps. This report highlights the importance of correlating clinical picture with muscle pathology changes along with judicious use of magnetic resonance imaging and serological studies to establish a definite diagnosis.
Inclusion body myositis with granuloma formation in muscle tissue.
Sakai Kenji,Ikeda Yoshihisa,Ishida Chiho,Matsumoto Yasuko,Ono Kenjiro,Iwasa Kazuo,Yamada Masahito
Neuromuscular disorders : NMD
Inclusion body myositis is a form of inflammatory myopathy. We identified 4 cases of inclusion body myositis showing granuloma formation in muscle tissue and aimed to assess the features of this atypical form of inclusion body myositis. We retrospectively reviewed consecutive patients who satisfied European Neuromuscular Centre IBM Research Diagnostic Criteria 2011. Then, we assessed clinical profiles and pathological findings in patients with inclusion body myositis with granuloma and compared these findings with those of typical inclusion body myositis without granuloma. We identified 15 patients with inclusion body myositis. Four patients showed granuloma formation in muscle tissue in addition to typical pathological features of inclusion body myositis. Granulomas comprised a mixture of inflammatory cells, such as macrophages, epithelioid histiocytic cells, and lymphocytes. One patient was found to have mediastinal granulomatous lymphadenopathy; however, the evidence in other patients was insufficient for a diagnosis of systemic sarcoidosis. There were no significant differences between groups with and without granuloma regarding clinical manifestations, laboratory findings, response to immunomodulating therapies, or myopathological profiles. We established a new form of inclusion body myositis showing granuloma formation in muscle tissue. Inclusion body myositis and granuloma formation could have identical pathomechanisms concerning dysregulation of autophagy.
[Sarcoidosis and comorbidity: retrospective study of 32 cases].
Bonnet F,Dubuc J,Morlat P,Delbrel X,Doutre M S,de Witte S,Bernard N,Lacoste D,Longy-Boursier M,Beylot J
La Revue de medecine interne
PURPOSE:A retrospective study was set up to investigate active pathologic processes associated with sarcoidosis diagnosed in 32 patients. METHODS:Eighteen patients had two identified granulomatous localizations (56%) and 14 patients had three localizations or more (27%). Comorbidity was noticed in nine patients (28% of cases). Sarcoidosis was associated with an infectious disease five times (hepatitis C virus [HCV] infection three times, including one case after recombinant interferon alpha therapy, and HIV and HCV co-infection two times). The association of sarcoidosis with a chronic immunologic inflammatory disease was noticed four times (lupus erythematosus two times, myasthenia and primary biliary cirrhosis). Finally, in two cases sarcoidosis was associated with a neoplasia (non-Hodgkin's lymphoma in a co-infected HIV-HCV patient, ovarian cystadenocarcinoma in another patient). Sarcoidosis preceded or revealed the comorbidity four times.
High levels of homocysteine results in cerebral amyloid angiopathy in mice.
Li Jian-Guo,Praticò Domenico
Journal of Alzheimer's disease : JAD
High levels of homocysteine is a risk factor for developing Alzheimer's disease (AD), and the effect that this amino acid has on amyloid-β (Aβ) protein precursor metabolism is considered one of the potential mechanism(s) involved in this effect. However, despite consistent literature indicating that this condition results in brain parenchyma amyloidosis, no data are available on whether it may also influence the amount of Aβ deposited in the vasculature. To test this hypothesis, we implemented a model of diet-inducing high homocysteinemia in AD transgenic mice, 3xTg, and assessed them for the development of cerebral amyloid angiopathy (CAA). Compared with controls, mice with high homocysteine showed a significant increase in the amount of Aβ deposited in the brain vasculature, which was not associated with histological evidence of microhemorrhage occurrence. Mice with high homocysteine had a significant reduction in steady state level of the apolipoprotein E, which is a main Aβ chaperon protein, but no changes in its receptor, the low-density-lipoprotein-receptor-1. Our data demonstrate that a diet-induced high homocysteine level favors the development of CAA via a reduction of Aβ clearance and transport within the brain. Therapeutic approaches aimed at restoring brain apolipoprotein E levels should be considered in individuals carrying this environmental risk factor in order to reduce the incidence of homocysteine-dependent CAA.