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1.
PLoS One ; 18(1): e0280864, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36696385

RESUMO

BACKGROUND: Meningoencephalitis of unknown origin (MUO) is an inflammatory disease of the canine central nervous system (CNS) that shares several features with multiple sclerosis (MS) in humans. In approximately 95% of MS patients, ≥ two immunoglobulin G (IgG) oligoclonal bands (OCBs) are detectable exclusively in the cerebrospinal fluid (CSF). HYPOTHESIS/OBJECTIVES: To investigate OCBs in CSF and serum in dogs affected by MUO, intervertebral disc disease (IVDD), idiopathic epilepsy (IE), intracranial neoplasia (IN), steroid-responsive meningitis-arteritis (SRMA), and diseases outside the CNS. We hypothesize that the highest prevalence of CSF-specific OCBs (≥ two OCBs uniquely in the CSF) would be found in dogs affected by MUO. ANIMALS: Client-owned dogs (n = 121) presented to the neurology service due to neurological deficits. METHODS: Prospective study. Measurement of IgG concentration in CSF and serum via a canine IgG ELISA kit. OCB detection via isoelectric focusing (IEF) and immunoblot. RESULTS: Presence of CSF-specific OCBs was significantly higher in dogs with MUO (57%) compared to 22% in IN, 6% in IE, 15% in SRMA, 13% in IVDD, and 0% in the non-CNS group (p < .001). Dogs with MUO were 9.9 times more likely to show CSF-specific OCBs than all other diseases together (95% confidence interval, 3.7-26.4; p < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: MUO showed the highest prevalence of CSF-specific OCBs, indicating an inflammatory B cell response. Future studies are needed to evaluate the prevalence in the specific MUO subtypes and a possible similarity with human MS.


Assuntos
Arterite , Neoplasias Encefálicas , Meningite , Meningoencefalite , Esclerose Múltipla , Humanos , Cães , Animais , Bandas Oligoclonais/líquido cefalorraquidiano , Estudos Prospectivos , Esclerose Múltipla/diagnóstico , Meningoencefalite/veterinária , Meningite/veterinária , Imunoglobulina G/líquido cefalorraquidiano , Arterite/veterinária
2.
J Neurol Sci ; 445: 120540, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36608627

RESUMO

BACKGROUND: Antibodies against glutamic acid decarboxylase (GAD-abs) at high serum levels are associated with diverse autoimmune neurological syndromes (AINS), including cerebellar ataxia, epilepsy, limbic encephalitis and stiff-person syndrome. The impact of low serum GAD-ab levels in patients with suspected AINS remains controversial. Specific intrathecal GAD-ab synthesis may serve as a marker for GAD-ab-associated nervous system autoimmunity. We present characteristics of a multicentric patient cohort with suspected AINS associated with GAD antibodies (SAINS-GAD+) and explore the relevance of serum GAD-ab levels and intrathecal GAD-ab synthesis. METHODS: All patients with SAINS-GAD+ included in the registry of the German Network for Research on Autoimmune Encephalitis (GENERATE) from 2011 to 2019 were analyzed. High serum GAD-ab levels were defined as RIA>2000 U/mL, ELISA>1000 U/mL, or as a positive staining pattern on cell-based assays. RESULTS: One-hundred-one patients were analyzed. In descending order they presented with epilepsy/limbic encephalitis (39%), cerebellar ataxia (28%), stiff person syndrome (22%), and overlap syndrome (12%). Immunotherapy was administered in 89% of cases with improvements in 46%. 35% of SAINS-GAD+ patients had low GAD-ab serum levels. Notably, unmatched oligoclonal bands in CSF but not in serum were more frequent in patients with low GAD-ab serum levels. GAD-ab-levels (high/low) and intrathecal GAD-ab synthesis (present or not) did not impact clinical characteristics and outcome. CONCLUSIONS: Overall, immunotherapy in SAINS-GAD+ was moderately effective. Serum GAD-ab levels and the absence or presence of intrathecal GAD-ab synthesis did not predict clinical characteristics or outcomes in SAINS-GAD+. The detection of unmatched oligoclonal bands might outweigh low GAD-ab serum levels.


Assuntos
Ataxia Cerebelar , Encefalite Límbica , Rigidez Muscular Espasmódica , Humanos , Ataxia Cerebelar/tratamento farmacológico , Glutamato Descarboxilase , Autoanticorpos , Bandas Oligoclonais , Encefalite Límbica/terapia , Rigidez Muscular Espasmódica/terapia
3.
Egypt J Immunol ; 30(1): 42-48, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36591957

RESUMO

Multiple sclerosis (MS) is a chronic autoimmune-mediated demyelinating disease of the central nervous system (CNS) that is usually associated with varying degrees of progressive disability. Chitinase-3-like protein-1 (CHI3L1) has attracted growing attention as a marker of ongoing inflammation and oncogenic transformation. The aim of this work was to assess the diagnostic accuracy of CHI3L1 versus IgG oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) of newly diagnosed relapsing remitting MS (RRMS) patients to throw light on a new simpler non subjective potential diagnostic marker in MS. This cross-sectional study of MS patients was carried at Ain Shams University Hospitals during the period from January 2021 till January 2022. Subjects included in this study were 40 patients diagnosed as having RRMS, based on their magnetic resonance imaging (MRI) findings, clinical presentation and according to the revised McDonald criteria 2017. The group included 10 males and 30 females; their ages ranged from 20 to 45 years. We found a significant correlation between CSF CHI3L1 levels and presence of oligoclonal bands (p=0.001), and that a cut off value of 30 ng/ml could be used for diagnosis of MS with sensitivity 84.85% and specificity 85.71%. A significant association was also found between CHI3L1 levels in CSF and Expanded Disability Status Scale (EDSS) score (p=0.002). We concluded that there were high levels of CHI3L1 in the CSF of MS patients and there was a significant correlation between CHI3L1 and oligoclonal bands and that CHI3L1 may be considered a promising diagnostic marker of MS.


Assuntos
Quitinases , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla/diagnóstico , Bandas Oligoclonais , Biomarcadores , Quitinases/líquido cefalorraquidiano , Estudos Transversais
4.
Mult Scler Relat Disord ; 68: 104397, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36544326

RESUMO

BACKGROUND: The presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in cerebrospinal fluid is associated with a more severe clinical multiple sclerosis (MS) course. OBJECTIVE: To investigate LS-OCMB as a prognostic biomarker of cognitive long-term outcomes in MS. METHODS: Ninety-nine patients underwent neuropsychological assessment. Cognitive performance between LS-OCMB- and LS-OCMB+ patients was compared adjusting by age, education, anxiety-depression, disease duration, and disability. RESULTS: LS-OCMB+ patients of ∼13 years of disease duration performed worse on Symbol Digit Modalities Test (SDMT) (p = 0.005). CONCLUSION: LS-OCMB+ perform worse on information processing speed and working memory (SDMT), suggesting that LS-OCMB could be a useful biomarker for long-term cognitive outcomes.


Assuntos
Esclerose Múltipla , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/líquido cefalorraquidiano , Bandas Oligoclonais/líquido cefalorraquidiano , Imunoglobulina M , Cognição , Testes Neuropsicológicos
5.
Medicina (Kaunas) ; 58(11)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36363469

RESUMO

Background: The positive implications of using free light chains in diagnosing multiple sclerosis have increasingly gained considerable interest in medical research and the scientific community. It is often presumed that free light chains, particularly kappa and lambda free light chains, are of practical use and are associated with a higher probability of obtaining positive results compared to oligoclonal bands. The primary purpose of the current paper was to conduct a systematic review to assess the up-to-date methods for diagnosing multiple sclerosis using kappa and lambda free light chains. Method: An organized literature search was performed across four electronic sources, including Google Scholar, Web of Science, Embase, and MEDLINE. The sources analyzed in this systematic review and meta-analysis comprise randomized clinical trials, prospective cohort studies, retrospective studies, controlled clinical trials, and systematic reviews. Results: The review contains 116 reports that includes 1204 participants. The final selection includes a vast array of preexisting literature concerning the study topic: 35 randomized clinical trials, 21 prospective cohort studies, 19 retrospective studies, 22 controlled clinical trials, and 13 systematic reviews. Discussion: The incorporated literature sources provided integral insights into the benefits of free light chain diagnostics for multiple sclerosis. It was also evident that the use of free light chains in the diagnosis of clinically isolated syndrome (CIS) and multiple sclerosis is relatively fast and inexpensive in comparison to other conventional state-of-the-art diagnostic methods, e.g., using oligoclonal bands (OCBs).


Assuntos
Esclerose Múltipla , Bandas Oligoclonais , Humanos , Esclerose Múltipla/diagnóstico , Estudos Retrospectivos , Estudos Prospectivos , Cadeias kappa de Imunoglobulina , Cadeias lambda de Imunoglobulina , Cadeias Leves de Imunoglobulina , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Front Immunol ; 13: 1000912, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275763

RESUMO

A 27-year-old woman was admitted to our hospital for fever, associated with headache, nausea, and vomiting, and she rapidly developed mild left facial nerve palsy and diplopia. Neurological examination revealed mild meningitis associated with bilateral VI cranial nerve palsy and mild left facial palsy. As central nervous system (CNS) infection was suspected, a diagnostic lumbar puncture was performed, which revealed 1,677 cells/µl, 70% of which were polymorphonuclear leukocytes. Moreover, multiplex PCR immunoassay was positive for Neisseria meningitidis, supporting the diagnosis of bacterial meningitis. Finally, IgG oligoclonal bands (IgGOB) were absent in serum and cerebrospinal fluid (CSF). Therefore, ceftriaxone antibiotic therapy was started, and in the following days, the patient's signs and symptoms improved, with complete remission of diplopia and meningeal signs within a week. On the contrary, left facial nerve palsy progressively worsened into a severe bilateral deficit. A second lumbar puncture was therefore performed: the CSF analysis revealed a remarkable decrease of pleocytosis with a qualitative modification (only lymphocytes), and oligoclonal IgG bands were present. A new brain MRI was performed, showing a bilateral gadolinium enhancement of the intrameatal VII and VIII cranial nerves bilaterally. Due to suspicion of para-infectious etiology, the patient was treated with oral steroid (prednisolone 1 mg/kg/day), with a progressive and complete regression of the symptoms. We suggest that in this case, after a pathogen-driven immunological response (characterized by relevant CSF mixed pleocytosis and no evidence of IgGOB), a para-infectious adaptive immunity-driven reaction (with mild lymphocyte pleocytosis and pattern III IgGOB) against VII and VIII cranial nerves started. Indeed, steroid administration caused a rapid and complete restoration of cranial nerve function.


Assuntos
Doenças dos Nervos Cranianos , Meningites Bacterianas , Feminino , Humanos , Adulto , Bandas Oligoclonais , Ceftriaxona , Gadolínio , Diplopia , Leucocitose , Meios de Contraste , Doenças dos Nervos Cranianos/diagnóstico , Doenças dos Nervos Cranianos/tratamento farmacológico , Doenças dos Nervos Cranianos/etiologia , Prednisolona , Meningites Bacterianas/complicações , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/tratamento farmacológico , Paralisia , Imunoglobulina G , Antibacterianos
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(5): 1453-1463, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36208249

RESUMO

OBJECTIVE: To investigate the clinical value of oligoclonal bands (OB) in patients with multiple myeloma (MM). METHODS: The laboratory test and clinical data of 624 newly diagnosed MM patients admitted to Blood Diseases Hospital of Chinese Academy of Medical Sciences from January 2013 to December 2019 were retrospectively analyzed, including 30 patients with OB, and the clinical characteristics, treatment effects and survival of OB and non-OB patients were analyzed and compared. RESULTS: OB occurred in 11.8% (22/187) of patients who received autologous stem cell transplantation(ASCT) and only 1.8% (8/437) of patients who did not receive ASCT (P=0.000). The median time to the appearance of oligoclonal bands was 3.2(0.6-10.5) months after transplantation. The M protein types of oligoclonal bands mainly include IgG κ, IgG λ, IgM λ and λ light chains. In the presence of oligoclonal bands, 90% of patients were evaluated as complete remission (CR) and above. There were no statistically significant differences in disease stage, tumor burden, and genetic abnormalities between OB and non-OB patients. Among the all patients, the prognosis of OB patients was significantly better than that of non-OB patients, and OB patients showed deeper disease remission (significantly higher CR rate, MRD negative rate, and longer MRD negative duration). Among patients who underwent ASCT, OB patients showed earlier immune recovery, but the depth of treatment response and survival outcomes were similar between OB and non-OB patients, it was no statistically difference. Although OB patients showed earlier immune reconstitution, this did not translate into better survival, suggesting that the better prognosis of OB patients was mainly related to deeper and durable remission rather than early immune reconstitution. Further analysis in patients who received ASCT and obtained MRD negative indicated that there was no additional survival benefit in patients with OB. CONCLUSION: The better prognosis of OB patients may be related to the deeper treatment response, but not to the early immune reconstitution. The appearance of OB is only a sign of deep remission and early immune reconstitution in patients, it cannot be translated into survival benefit of MM patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Imunoglobulina G , Imunoglobulina M , Bandas Oligoclonais , Estudos Retrospectivos , Transplante Autólogo
8.
Medicine (Baltimore) ; 101(39): e30814, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36181106

RESUMO

INTRODUCTION: Cases with organ-specific and systemic vasculitis associated with corona virus disease 2019 (COVID-19) vaccination have been reported. However, acute partial transverse myelitis (APTM) is rare adverse events following received COVID-19 vaccines. To the best of our knowledge, there is no report on vaccine-associated APTM accompanied by possible concurrent vasculitis. Herein we present a case with possible concurrent spinal vasculitis and APTM following the second dose of inactivated COVID-19 vaccine. CASE SUMMARY: A 33-year-old man presented with weakness of left lower limb and aberrant sensation of his left lower trunk and limb (from T9 level to toes) for 2 days following receipt of an inactivated COVID-19 vaccine. Remarkable demyelinating lesion at T7 spinal cord was showed by 3.0T magnetic resonance imaging (MRI) scan. Moreover, vertebral bodies of T3-T7 also presented high signal in T-2 weighted imaging (T2WI) accompanied by multiple sites of flowing void effect indicating possible vasculitis. Oligoclonal band was positive in cerebrospinal fluid (CSF) while it was negative in sera. Intravenous methylprednisolone (1 g/d) was administrated for 5 days followed by subsequent dose-tapering prednisone. His limb weakness and aberrant sensation both improved and he was able to walk unaided after treatment. The MRI recheck also showed remarkable improvement on the lesions in spinal cord and vertebral bodies. CONCLUSION: this case illustrates the concurrence of possible vasculitis in vertebral bodies and acute transverse myelitis (ATM) following COVID-19 vaccination.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Mielite Transversa , Vasculite , Corpo Vertebral , Adulto , COVID-19/complicações , Vacinas contra COVID-19/efeitos adversos , Humanos , Imageamento por Ressonância Magnética , Masculino , Metilprednisolona/uso terapêutico , Mielite Transversa/induzido quimicamente , Bandas Oligoclonais , Prednisona/uso terapêutico , Vacinação , Vasculite/induzido quimicamente , Vasculite/tratamento farmacológico
9.
Rev. neurol. (Ed. impr.) ; 75(7): 181-187, Oct 1, 2022. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-209615

RESUMO

Introducción: La determinación de bandas oligoclonales (BOC) en el líquido cefalorraquídeo es esencial para el diagnóstico de esclerosis múltiple (EM). El índice kappa es un biomarcador con una sensibilidad y una especificidad comparables a las de las BOC. El objetivo de este trabajo fue estudiar su utilidad y calcular el punto de corte óptimo. Material y métodos. Estudio observacional de muestras recibidas en el servicio de inmunología de referencia para Aragón entre enero de 2019 y junio de 2020. Se determinó el valor del índice kappa y el índice IgG. Se trazaron y compararon curvas ROC frente a la detección de BOC y el diagnóstico de EM. Se calcularon valores de sensibilidad y especificidad y el punto de corte óptimo. Resultados: Se analizaron 181 pacientes (59,7%, mujeres; edad media, 47,62 ± 17,8 años). El grupo de EM demostró valores estadísticamente superiores de índice kappa (66,62 frente a 0,02; p < 0,001). En el análisis de curvas ROC, el índice kappa demostró un área bajo la curva superior al índice IgG en la detección de BOC+ (0,93 frente a 0,83; p < 0,002) y el diagnóstico de EM (0,91 frente a 0,83; p < 0,021). El punto de corte óptimo del índice kappa para la detección de BOC fue 5,02 (sensibilidad y especificidad, 0,92) y 7,58 para el diagnóstico de EM (sensibilidad, 0,85; especificidad, 0,94). Conclusiones: El índice kappa es un biomarcador útil en el diagnóstico de la EM. Su determinación es un proceso automático y rápido, con valores de sensibilidad y especificidad superiores al índice IgG. Todavía se debe llegar a un consenso sobre el punto de corte óptimo para su positividad, si bien, en nuestro medio, un punto de corte de 5,02 parece razonable.(AU)


INTRODUCTION: Detection of oligoclonal bands (OCB) in CSF is essential in the diagnosis of multiple sclerosis (MS). Kappa-index is a promising biomarker, with sensitivity and sensibility values comparable to those of OCB. Our objective was to investigate kappa-index utility in the diagnosis work-up for MS and to determine the optimal cut-off point for our population. Material and methods. Observational study of consecutive samples received in the Immunology lab department in a third level hospital between January 2019 to June 2020. Kappa-index and IgG index were measured. ROC analysis for screening of OCB and for diagnosis of MS was conducted. Sensibility, specificity and the optimal cut-off points were determined. RESULTS: 181 samples were included (59.7% females; age, 47.62 ± 17.8 years). Patients in the EM group presented significantly higher kappa-index level than patients without an EM diagnosis (66.62 versus 0.02; p < 0.001). ROC analysis reported a better area under the curve for the kappa-index than the IgG index for the detection of BOC (0.93 versus 0.83; p < 0.002) and the diagnosis of EM (0.91 versus 0.83; p < 0.021). An optimal cut-off point of 5.02 was determined for the detection of BOC (sensibility and specificity, 0.92) and of 7.58 for the diagnosis of EM (sensibility, 0.85; specificity, 0.94). CONCLUSIONS: Kappa-index is an useful biomarker in the diagnosis of MS. Its specificity and sensibility are superior to the IgG index. The optimal cut-off point has yet to be determined, but for our population a cut-off of 5.02 seems reasonable.(AU)


Assuntos
Humanos , Feminino , Esclerose Múltipla/diagnóstico , Bandas Oligoclonais , Líquido Cefalorraquidiano , Sensibilidade e Especificidade , Interpretação Estatística de Dados , Biomarcadores , Neurologia , Esclerose , Doenças Desmielinizantes
10.
Medicina (Kaunas) ; 58(9)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36143856

RESUMO

Background and Objectives: Multiple sclerosis (MS) is a demyelinating disease which usually manifests as clinically isolated syndrome (CIS). Approximately 70% of patients with CIS progress to MS. Therefore, there is a pressing need to identify the most accurate predictive factors of CIS developing into MS, some of which could be a clear clinical phenotype of early MS as well as lesions in magnetic resonance imaging (MRI), pathological findings in cerebrospinal fluid (CSF) and evoked potentials (EP) tests. The problem is of outstanding importance since early MS diagnosis and treatment prevents long-term disability. The aim of our study is to analyze the factors that could influence the progression of CIS to MS. Materials and Methods: This study is a retrospective data analysis which included patients with their primary CIS diagnosis between 1st January 2015 and 1st January 2020. The prevalence and predictive value of clinical symptoms, MRI lesions, pathological CSF and EP findings were evaluated in accordance with the final diagnosis and compared between the sexes and age groups. Results: Out of 138 CIS patients, 49 (35.5%) patients progressed to MS. MS patients were more likely to have a diminished sense of vibration and proprioception (χ2 = 9.033, p = 0.003) as well as spinal cord MRI lesions (χ2 = 7.209, p = 0.007) in comparison with the non-MS group. Positive oligoclonal bands (OCBs) in CSF (χ2 = 34.859, p ≤ 0.001) and pathological brainstem auditory evoked potential (BAEP) test findings (χ2 = 10.924, p ≤ 0.001) were more prevalent in the MS group. Diminished sense of vibration and proprioception increased the risk for developing MS by 13 times (p = 0.028), whereas positive OCBs in CSF increased the risk by 100 times (p < 0.001). MS patients that were older than 50 years were more likely to exhibit positive Babinski's reflex (χ2 = 6.993, p = 0.03), decreased muscle strength (χ2 = 13.481, p = 0.001), ataxia (χ2 = 8.135, p = 0.017), and diminished sense of vibration and proprioception (χ2 = 7.918, p = 0.019) in comparison with both younger age groups. Conclusions: Diminished sense of vibration and proprioception, spinal cord MRI lesions, positive OCBs and pathological BAEP test findings were more common among patients that developed MS. Diminished sense of vibration and proprioception along with positive CSF OCBs are predictors of CIS progressing to MS. Older patients that develop MS have more symptoms in general, such as positive Babinski's reflex, decreased muscle strength, ataxia, and diminished sense of vibration and proprioception.


Assuntos
Doenças Desmielinizantes , Esclerose Múltipla , Ataxia , Doenças Desmielinizantes/epidemiologia , Doenças Desmielinizantes/patologia , Progressão da Doença , Humanos , Lituânia/epidemiologia , Imageamento por Ressonância Magnética , Esclerose Múltipla/epidemiologia , Bandas Oligoclonais/líquido cefalorraquidiano , Estudos Retrospectivos
11.
Neurol Sci ; 43(12): 6951-6954, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36121546

RESUMO

We describe 3 cases of solitary sclerosis (SS), a rare condition characterized by a single inflammatory demyelinating lesion in the white matter of the brain or spinal cord. All patients had progressive limb motor impairment (patient 1, 66-year-old female: left spastic hemiparesis; patient 2, 39-year-old male: right spastic hemiparesis; patient 3, 42-year-old female: proximally predominant left upper limb weakness with amyotrophy and fasciculations). In all patients, MRI disclosed a single small T2-hyperintense demyelinating lesion: in the right anterior paramedian upper medulla, in the median-left paramedian anterior lower medulla, and in the left paramedian anterior cervical spinal cord at C4 level, respectively. In patients 1 and 2, transcranial magnetic stimulation (TMS) demonstrated altered motor evoked potentials (MEPs) and increased central motor conduction time (CMCT) in the affected limbs; in patient 3, needle EMG revealed chronic neurogenic changes in C5-C7 muscles of left upper limb. Patients 1 and 2 had normal brain 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). CSF analysis demonstrated IgG oligoclonal bands in all patients. In patients 2 and 3, levels of neurofilament light chain (NFL) in CSF and serum, respectively, were within normal limits. The three cases were consistent with the diagnosis of SS. Notably, while the first two cases mimicked Mills' syndrome (the hemiparetic variant of primary lateral sclerosis, PLS), the third one was rather reminiscent of amyotrophic lateral sclerosis (ALS). This suggests including SS in the differential diagnosis not only of PLS, but also of ALS. We also report the first quantification of NFL levels in SS.


Assuntos
Esclerose Amiotrófica Lateral , Doença dos Neurônios Motores , Humanos , Masculino , Feminino , Idoso , Adulto , Esclerose Amiotrófica Lateral/diagnóstico , Esclerose Amiotrófica Lateral/patologia , Bandas Oligoclonais , Esclerose/patologia , Espasticidade Muscular , Doença dos Neurônios Motores/diagnóstico , Doença dos Neurônios Motores/patologia , Neurônios Motores/patologia , Síndrome , Paresia
12.
Sci Rep ; 12(1): 16425, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-36180495

RESUMO

In multiple sclerosis (MS) disease, the importance of the intrathecal B cell response classically revealed as IgG oligoclonal bands (OCB) in cerebrospinal fluid (CSF) was reaffirmed again in the recently revised diagnostic criteria. We aimed to optimize Laboratory investigation by testing the performance of new B cell-related molecules in CSF (Ig free light chains (FLCκ and λ) and CXCL13 (B-Cell Attracting chemokine1)) for MS diagnosis. 320 paired (CSF-serum) samples were collected from 160 patients with MS (n = 82) and non-MS diseases (n = 78). All patients benefited from IgG index determination, OCB detection, CSF CXCL13 and FLC (κ and λ) measurement in CSF and serum for metrics calculation (κ/λ ratio, FLC-related indexes, and κFLC-intrathecal fraction (IF)). CXCL13 and FLC metrics in CSF were higher in patients with MS and positive OCB. As expected, κFLC metrics-in particular, κFLC index and κFLC IF-had the highest accuracy for MS diagnosis. κ index showed the best performance (sensitivity 83% and specificity 91.7%) at a cut-off of 14.9. Most of the FLC-related parameters were positively correlated with IgG index and the level of CXCL13. In conclusion, the quantitative, standardizable, and technically simple CSF FLCκ metrics seem to be reliable for MS diagnosis, but could not replace OCB detection. CXCL13 appears to be an effective parameter reflecting the intrathecal B cell response. An optimized way for CSF testing combining the conventional and the new B cell-related parameters is proposed in this study.


Assuntos
Esclerose Múltipla , Bandas Oligoclonais , Biomarcadores , Humanos , Imunoglobulina G/líquido cefalorraquidiano , Cadeias Leves de Imunoglobulina , Cadeias kappa de Imunoglobulina , Bandas Oligoclonais/líquido cefalorraquidiano
13.
Rev Neurol ; 75(7): 181-187, 2022 10 01.
Artigo em Espanhol | MEDLINE | ID: mdl-36169324

RESUMO

INTRODUCTION: Detection of oligoclonal bands (OCB) in CSF is essential in the diagnosis of multiple sclerosis (MS). Kappa-index is a promising biomarker, with sensitivity and sensibility values comparable to those of OCB. Our objective was to investigate kappa-index utility in the diagnosis work-up for MS and to determine the optimal cut-off point for our population. MATERIAL AND METHODS: Observational study of consecutive samples received in the Immunology lab department in a third level hospital between January 2019 to June 2020. Kappa-index and IgG index were measured. ROC analysis for screening of OCB and for diagnosis of MS was conducted. Sensibility, specificity and the optimal cut-off points were determined. RESULTS: 181 samples were included (59.7% females; age, 47.62 ± 17.8 years). Patients in the EM group presented significantly higher kappa-index level than patients without an EM diagnosis (66.62 versus 0.02; p < 0.001). ROC analysis reported a better area under the curve for the kappa-index than the IgG index for the detection of BOC (0.93 versus 0.83; p < 0.002) and the diagnosis of EM (0.91 versus 0.83; p < 0.021). An optimal cut-off point of 5.02 was determined for the detection of BOC (sensibility and specificity, 0.92) and of 7.58 for the diagnosis of EM (sensibility, 0.85; specificity, 0.94). CONCLUSIONS: Kappa-index is an useful biomarker in the diagnosis of MS. Its specificity and sensibility are superior to the IgG index. The optimal cut-off point has yet to be determined, but for our population a cut-off of 5.02 seems reasonable.


TITLE: Utilidad del índice kappa en el diagnóstico de esclerosis múltiple y validación de valores de referencia en la Comunidad de Aragón.Introducción. La determinación de bandas oligoclonales (BOC) en el líquido cefalorraquídeo es esencial para el diagnóstico de esclerosis múltiple (EM). El índice kappa es un biomarcador con una sensibilidad y una especificidad comparables a las de las BOC. El objetivo de este trabajo fue estudiar su utilidad y calcular el punto de corte óptimo. Material y métodos. Estudio observacional de muestras recibidas en el servicio de inmunología de referencia para Aragón entre enero de 2019 y junio de 2020. Se determinó el valor del índice kappa y el índice IgG. Se trazaron y compararon curvas ROC frente a la detección de BOC y el diagnóstico de EM. Se calcularon valores de sensibilidad y especificidad y el punto de corte óptimo. Resultados. Se analizaron 181 pacientes (59,7%, mujeres; edad media, 47,62 ± 17,8 años). El grupo de EM demostró valores estadísticamente superiores de índice kappa (66,62 frente a 0,02; p menor de 0,001). En el análisis de curvas ROC, el índice kappa demostró un área bajo la curva superior al índice IgG en la detección de BOC+ (0,93 frente a 0,83; p menor de 0,002) y el diagnóstico de EM (0,91 frente a 0,83; p menor de 0,021). El punto de corte óptimo del índice kappa para la detección de BOC fue 5,02 (sensibilidad y especificidad, 0,92) y 7,58 para el diagnóstico de EM (sensibilidad, 0,85; especificidad, 0,94). Conclusiones. El índice kappa es un biomarcador útil en el diagnóstico de la EM. Su determinación es un proceso automático y rápido, con valores de sensibilidad y especificidad superiores al índice IgG. Todavía se debe llegar a un consenso sobre el punto de corte óptimo para su positividad, si bien, en nuestro medio, un punto de corte de 5,02 parece razonable.


Assuntos
Esclerose Múltipla , Bandas Oligoclonais , Adulto , Idoso , Biomarcadores , Feminino , Humanos , Imunoglobulina G , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Valores de Referência
14.
Clin Chem ; 68(9): 1134-1150, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35934949

RESUMO

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated central nervous system (CNS) inflammatory demyelinating disease in which analysis of clinical presentation, imaging studies, and laboratory tests aid in diagnosis. CONTENT: This review discusses laboratory tests ordered to rule out and rule in MS, such as the traditional measurement of cerebrospinal fluid (CSF) IgG index and oligoclonal bands. Biomarkers discovered in the past 2 decades, such as aquaporin-4 (AQP4) antibodies and myelin oligodendrocyte glycoprotein (MOG) antibodies, have been incorporated into clinical practice in the diagnosis of disorders referred to as MS mimics. The importance of test selection, assay methodology, optimal sample for testing, and diagnostic utility of these biomarkers is reviewed. Other laboratory testing that can aid in the differentiation between MS and these biomarker-defined CNS demyelinating diseases is described. There is a focus on emerging biomarkers such as the use of kappa immunoglobulin free light chain concentration in CSF and kappa CSF index measurement as an alternative to oligoclonal bands which has a potential for an improvement in laboratory workflows. Finally, the role of biomarkers of disease activity and prognosis are discussed, including neurofilament light chain, glial fibrillary acidic protein, and myelin basic protein. Future perspectives with improved laboratory testing tools and discovery of additional biomarkers are provided. SUMMARY: Laboratory testing for demyelinating disorders using CSF and serum are routine practices that can benefit from an update, as novel biomarker-defined entities have reduced the potential for MS misdiagnosis, and CSF/serum biomarkers reinstated in the diagnostic criteria of MS.


Assuntos
Aquaporinas , Esclerose Múltipla , Autoanticorpos , Biomarcadores , Proteína Glial Fibrilar Ácida , Humanos , Imunoglobulina G , Cadeias kappa de Imunoglobulina , Esclerose Múltipla/diagnóstico , Proteína Básica da Mielina , Glicoproteína Mielina-Oligodendrócito , Bandas Oligoclonais/líquido cefalorraquidiano
15.
Front Immunol ; 13: 967953, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36032114

RESUMO

Background: Emerging evidence supports that determination of intrathecal immunoglobulin M (IgM) synthesis (ITMS) and neurofilament light (NfL) concentration in cerebrospinal fluid (CSF) may be clinically useful as disease severity biomarkers in relapsing-remitting multiple sclerosis (RRMS). Methods: Monocentric observational longitudinal cohort study in which prospectively collected data were retrospectively retrieved. Included were patients with RRMS (n=457) who had a diagnostic investigation including analysis of ITMS and CSF neurofilament light (cNfL). ITMS was calculated with the linear index formula, the intrathecal fraction of IgM according to Reiber (IgMIF), and by qualitative determination of oligoclonal IgM bands (OCMB). Univariable and multivariable models were performed to predict Evidence of Disease Activity-3 (EDA-3) status within 24 months from onset, and the risk of Expanded Disability Status Score (EDSS) ≥3 and ≥6. Results: All investigated methods to calculate ITMS significantly predicted evidence of disease activity (EDA-3) within 24 months. IgMIF>0% showed the strongest association with EDA-3 status (adjusted hazard ratio [aHR] 3.7, 95%CI 2.7-5, p<0.001). Combining IgM-index>0.1 or OCMB with increased cNfL were strong predictors of EDSS≥3 (for cNfL + /IgM-index + : aHR 4.6, 95%CI 2.6-8.2, p<0.001) and EDSS≥6 (aHR 8.2, 95%CI 2.3-30, p<0.001). Conclusions: In a real-world setting, ITMS was a useful biomarker in early RRMS to predict disabling MS and its prognostic value was even stronger in combination with cNfL. Our data suggest that determination of ITMS and cNfL should be included in the diagnostic work-up of RRMS for prognostic purposes and in decisions of disease-modifying therapy.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Biomarcadores , Humanos , Imunoglobulina M , Filamentos Intermediários , Estudos Longitudinais , Bandas Oligoclonais , Estudos Retrospectivos
16.
Adv Clin Chem ; 109: 129-163, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35953125

RESUMO

Oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) represent an indicator of IgG and IgM immunoglobulins intrathecal synthesis in the central nervous system (CNS). The techniques and detection methods for their determination have evolved from the beginning to isoelectric focusing on an agarose gel as the gold standard technique and immunodetection as the reference method. The evolution, both in techniques and methods for detection of IgG and IgM OCBs is evaluated in this review. In addition to the significance of the presence of a single band of IgG immunoglobulin in CSF, IgG OCBs within the diagnostic criteria of multiple sclerosis (MS), the prevalence of IgG OCBs and the effect of latitude in MS, as well as the clinical and immunological involvement of OCBs (IgG and IgM) in MS and other neurological diseases.


Assuntos
Esclerose Múltipla , Bandas Oligoclonais , Humanos , Imunoglobulina G/líquido cefalorraquidiano , Imunoglobulina M , Focalização Isoelétrica/métodos , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico , Bandas Oligoclonais/líquido cefalorraquidiano
17.
Mult Scler Relat Disord ; 66: 104008, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35863128

RESUMO

BACKGROUND: Our aim was to propose criteria to distinguish multiple sclerosis (MS) from acute disseminated encephalomyelitis (ADEM) at onset based on age at onset, sex, cerebrospinl fluid (CSF)-specific oligoclonal bands, and MRI. METHODS: A neuroradiologist undertook retrospective evaluation of the baseline magnetic resonance imaging (MRI) in a nationwide cohort of children with medical record-validated MS (n = 67) and monophasic ADEM (n = 46). Children with ADEM had at least 5 years of follow-up for relapse. We used forward stepwise conditional logistic regression to develop our criteria based on age at onset, sex, CSF-specific oligoclonal bands, and MRI. We undertook sensitivity analyses using children with ADEM including encephalopathy and polyfocal neurological deficits and in those with onset between 11 and 17 years of age. We estimated accuracy statistics from our criteria and all previously proposed MRI criteria to distinguish MS and ADEM. RESULTS: The best performing criteria to differentiate MS from ADEM were scoring at least three points in the following categories: presence of CSF-specific oligoclonal bands (2 points), occipital lesion (1 point), age 11-17 years (1 point), female sex (1 point). These criteria gave highly reliable discrimination with sensitivity of 95% (95% CI=89%-100%), specificity of 100% (95% CI=100%-100%), and area under the curve of 98% (95% CI=95%-100%). The best performing MRI criteria had area under the curve of 84% (95% CI=78%-91%). Previously proposed MRI criteria had the following areas under the curve: Callen (75%), KIDMUS (82%), and McDonald 2017 criteria (68%). CONCLUSION: Combining sex, age at onset, CSF-specific oligoclonal bands, and MRI gives highly reliable differentiation between pediatric MS and monophasic ADEM at onset.


Assuntos
Encefalomielite Aguda Disseminada , Esclerose Múltipla , Adolescente , Criança , Estudos de Coortes , Encefalomielite Aguda Disseminada/diagnóstico por imagem , Encefalomielite Aguda Disseminada/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Bandas Oligoclonais , Estudos Retrospectivos
18.
Neurology ; 99(9): 387-392, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35794020

RESUMO

A brainstem syndrome is recognizable in patients presenting with a combination of visual disturbances, incoordination, gait problems, speech and swallowing difficulties, and new-onset sleep symptomatology. Brainstem disorders of subacute onset (onset and progression with accumulation of disabling deficits in 6-12 weeks) are generally of autoimmune, infectious, inflammatory, or infiltrative neoplastic cause. An autoimmune or infectious brainstem disorder may be referred to as brainstem encephalitis or rhombencephalitis. We describe a patient with paraneoplastic autoimmune rhombencephalitis, in whom diagnostic clues included the following: diverse visual and sleep symptoms, trismus, and choking in the history; see-saw nystagmus, opsoclonus, dysarthria, jaw dystonia, and episodic laryngospasm on examination; subtle but longitudinal and nonenhancing T2 MRI abnormalities in the brainstem and upper cervical cord; and oligoclonal bands in the CSF. His movement disorder-specific neural IgG profile revealed ANNA-2 (anti-Ri) and KLHL-11-IgG. Both are biomarkers of paraneoplastic brainstem encephalitis. KLCHL-11-IgG has been reported to accompany germ cell tumors, which was found in a solitary metastasis to the left inguinal lymph node in our patient, along with an atrophic left testis. Multidisciplinary treatment (autoimmune neurology, sleep medicine, ophthalmology, and physiatry) led to significant clinical improvements. This case provides a framework for the evaluation of patients with subacute-onset brainstem syndromes and the investigation and management of those with paraneoplastic and other autoimmune diseases.


Assuntos
Encefalite , Transtornos dos Movimentos , Distúrbios do Início e da Manutenção do Sono , Adulto , Autoanticorpos , Raciocínio Clínico , Encefalite/diagnóstico , Humanos , Imunoglobulina G , Masculino , Transtornos dos Movimentos/complicações , Bandas Oligoclonais , Distúrbios do Início e da Manutenção do Sono/complicações , Trismo
19.
J Infect Dev Ctries ; 16(6): 1096-1100, 2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-35797306

RESUMO

The oligoclonal band indicates presence of antibodies specific to the disease, possibly due to the activation of certain clones of B lymphocytes. This intrathecal immunoglobin synthesis can be persistent for months to years, for example, in respons to paramyxoviruses, herpes virus, coxsackievirus, and Treponema pallidum; or can be synthesized for life, for example in multiple sclerosis and subacute sclerosing panencephalitis (SSPE). We report a case of SSPE in a 15-year-old male patient. The patient had myoclonic jerks that occurred in the thoracal femoral region. Necessary laboratory tests identified reactive anti-measles IgG, which indicates a previous measles infection or exposure to vaccination. This report describes the usefulness of the oligoclonal bands in the diagnosis of the neurodegenerative disease SSPE that is progressive and fatal to the central nervous system due to persistent measles virus infection in the gray and white matter.


Assuntos
Doenças Neurodegenerativas , Panencefalite Esclerosante Subaguda , Adolescente , Anticorpos Antivirais , Técnicas de Laboratório Clínico , Humanos , Imunoglobulina G , Masculino , Vírus do Sarampo , Bandas Oligoclonais , Panencefalite Esclerosante Subaguda/diagnóstico
20.
Brain ; 145(11): 3931-3942, 2022 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-35727945

RESUMO

Intrathecal production of kappa free light chains occurs in multiple sclerosis and can be measured using the kappa free light chain index. Kappa free light chain index values can be determined more easily than oligoclonal bands detection and seem more sensitive than the immunoglobulin (Ig)G index to diagnose multiple sclerosis. We assessed the value of oligoclonal bands, kappa free light chain index cut-offs 5.9, 6.6 and 10.61, and IgG index to diagnose multiple sclerosis with prospectively acquired data from a clinically isolated syndrome inception cohort. We selected patients with sufficient data to determine oligoclonal bands positivity, MRI dissemination in space and time, IgG index and sufficient quantities of paired CSF and blood samples to determine kappa free light chain indexes (n = 214). We used Kendall's Tau coefficient to estimate concordance, calculated the number of additional diagnoses when adding each positive index to dissemination in space and positive oligoclonal bands, performed survival analyses for oligoclonal bands and each index with the outcomes second attack and 2017 MRI dissemination in space and time and estimated the diagnostic properties of oligoclonal bands and the different indexes for the previously mentioned outcomes at 5 years. Oligoclonal bands were positive in 138 patients (64.5%), kappa free light chain-5.9 in 136 (63.6%), kappa free light chain-6.6 in 135 (63.1%), kappa free light chain-10.61 in 126 (58.9%) and IgG index in 101 (47.2%). The highest concordance was between oligoclonal bands and kappa free light chain-6.6 (τ = 0.727) followed by oligoclonal bands and kappa free light chain-5.9 (τ = 0.716). Combining dissemination in space plus oligoclonal bands or kappa free light chain-5.9 increased the number of diagnosed patients by 11 (5.1%), with kappa free light chain-6.6 by 10 (4.7%), with kappa free light chain-10.61 by 9 (4.2%) and with IgG index by 3 (1.4%). Patients with positive oligoclonal bands or indexes reached second attack and MRI dissemination in space and time faster than patients with negative results (P < 0.0001 except IgG index in second attack: P = 0.016). In multivariable Cox models [adjusted hazard ratio (95% confidence interval)], the risk for second attack was very similar between kappa free light chain-5.9 [2.0 (0.9-4.3), P = 0.068] and kappa free light chain-6.6 [2.1 (1.1-4.2), P = 0.035]. The highest risk for MRI dissemination in space and time was demonstrated with kappa free light chain-5.9 [4.9 (2.5-9.6), P < 0.0001], followed by kappa free light chain-6.6 [3.4 (1.9-6.3), P < 0.0001]. Kappa free light chains-5.9 and -6.6 had a slightly higher diagnostic accuracy than oligoclonal bands for second attack (70.5, 71.1 and 67.8) and MRI dissemination in space and time (85.7, 85.1 and 81.0). Kappa free light chain indexes 5.9 and 6.6 performed slightly better than oligoclonal bands to assess multiple sclerosis risk and in terms of diagnostic accuracy. Given the concordance between oligoclonal bands and these indexes, we suggest using dissemination in space plus positive oligoclonal bands or positive kappa free light chain index as a modified criterion to diagnose multiple sclerosis.


Assuntos
Doenças Desmielinizantes , Esclerose Múltipla , Humanos , Bandas Oligoclonais , Cadeias kappa de Imunoglobulina , Doenças Desmielinizantes/diagnóstico , Esclerose Múltipla/diagnóstico por imagem , Imunoglobulina G
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