RESUMEN
BACKGROUND: Clinical exacerbations characterized with neurological symptoms are observed in around 10% of Behçet's disease (BD) patients and may culminate in severe disability. Although certain immunological factors have been associated with disease activity in neuro-Behçet's disease (NBD), biomarkers for monitoring the clinical outcome of NBD have not been properly investigated. METHODS: Levels of neurofilament light chain (NFL), homeobox protein Hox-B3 (HoxB3), and YKL-40 were measured in cerebrospinal fluid (CSF) samples of 23 parenchymal (n = 16) and nonparenchymal (n = 7) NBD patients obtained during NBD attacks by ELISA. Parameters of clinical progression and outcome were assessed for an average follow-up period of 3.9 ± 1.3 years. RESULTS: Parenchymal NBD patients showed elevated CSF levels of NFL, HoxB3, and YKL-40 as compared to nonparenchymal patients. NBD patients showing an increase in modified Rankin score (mRS) values during follow-up had significantly higher CSF NFL levels. Patients with relatively lower CSF NFL levels (<1000 ng/L) did not develop attacks or cognitive impairment interfering with daily life activities during follow-up. NFL levels correlated with disease duration and mRS at the last follow-up visit, while HoxB3 levels correlated with a number of attacks during follow-up. DISCUSSION: CSF level of NFL appears to predict the prospective somatic and cognitive disability in NBD patients and may thus be potentially used as a biomarker of clinical outcome in this disease.
Asunto(s)
Síndrome de Behçet , Humanos , Síndrome de Behçet/diagnóstico , Biomarcadores , Proteína 1 Similar a Quitinasa-3 , Filamentos Intermedios , Estudios ProspectivosRESUMEN
AIMS: Sexual dysfunction (SD) is common in female patients with multiple sclerosis (MS) reporting overactive bladder (OAB) symptoms. The aim of the study was to evaluate the effects of transcutaneous tibial nerve stimulation (TTNS) and pelvic floor muscle training (PFMT) with biofeedback on SD in female patients with MS reporting OAB symptoms. METHODS: Patients with overactive bladder and SD were allocated to receive TTNS or PFMT daily. Overactive bladder symptoms, sexual functions, and sexual quality of life were assessed at baseline and 6th weeks. Female Sexual Function Index (FSFI), Overactive Bladder Questionnaire (OABv-8), and Sexual Quality of Life-Female (SQoL-F) questionnaires were used. RESULTS: Thirty patients (TTNS = 10, PFMT = 20) were included in the study. Compared to baseline, total FSFIOABv-8, and SQoL-F scores improved in both TTNS (p = 0.005, p = 0.011, p = 0.444, respectively) and PFMT (p = 0.002, p = 0.001, p = 0.001, respectively) groups. Between-group comparisons did not show any significant differences. CONCLUSION: This study demonstrates the efficacy of both TTNS and PFMT for improving sexual function in female MS patients with OAB symptoms, but did not show superiority of any particular method. Further studies are required to investigate the differences between these two non-invasive methods.
Asunto(s)
Esclerosis Múltiple , Estimulación Eléctrica Transcutánea del Nervio , Vejiga Urinaria Hiperactiva , Femenino , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/terapia , Diafragma Pélvico , Calidad de Vida , Nervio Tibial , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/terapiaRESUMEN
BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are a group of antibody-mediated chronic inflammatory diseases of the central nervous system. Rituximab is a monoclonal antibody that leads to a reduction in disease activity. OBJECTIVE: To evaluate the efficacy of rituximab as monotherapy in NMOSD and to determine whether the efficacy varies depending on the presence of antibodies in this cohort. METHOD: This multicentre national retrospective study included patients with NMOSD treated with rituximab at least for 12 months from Turkey. The primary outcomes were the change in the annualised relapse rate, the Expanded Disability Status Scale (EDSS), the number of relapse and radiological activity-free patients. RESULTS: A total of 85 patients with NMOSD were included in the study. Of 85 patients, 58 (68.2%) were seropositive for anti-Aquaporin4-IgG (antI-AQP4-IgG). All patients were Anti-Myelin Oligodendrocyte Glycoprotein IgG (anti-MOG-IgG) negative. The median follow-up for rituximab treatment was 21 months (Q1 16-Q3 34.5). During rituximab treatment, the mean annualised relapse rate (ARR) significantly decreased from 1.45 ± 1.53 to 0.15 ± 0.34 (P < .001). In subgroup analyses, the mean ARR decreased from 1.61 ± 1.65 to 0.20 ± 0.39 in the seropositive group and 1.10 ± 1.19 to 0.05 ± 0.13 in the seronegative group. The mean EDSS improved from 3.98 ± 2.04 (prior to treatment onset) to 2.71 ± 1.59 (at follow-up) (P < .001). In the seropositive group, mean EDSS decreased from 3.94 ± 1.98 to 2.67 ± 1.54, and in the seronegative group, mean EDSS decreased from 4.07 ± 2.21 to 2.79 ± 1.73. There was no significant difference between anti-AQP4-IgG (+) and (-) groups in terms of ARR and EDSS. Sixty-four patients (75.2%) were relapse-free after the initiation of treatment. Seventy patients (82.3%) were radiological activity-free in the optic nerve, area postrema and brainstem. Additionally, 78 patients (91.7%) showed no spinal cord involvement after the treatment. CONCLUSION: Rituximab therapy is efficacious in the treatment of Turkish NMOSD patients independent of the presence of the anti-AQP4-IgG antibody.
Asunto(s)
Neuromielitis Óptica , Acuaporina 4 , Humanos , Neuromielitis Óptica/tratamiento farmacológico , Estudios Retrospectivos , Rituximab/uso terapéutico , TurquíaRESUMEN
AIMS: This study aimed to translate the eight-item Actionable Bladder Symptom Screening Tool (ABSST) and determine its psychometric properties in Turkish speaking subjects. METHODS: The study was conducted at the multiple sclerosis (MS) outpatient clinic of the Istanbul Faculty of Medicine, Istanbul University. First, the ABSST was translated into Turkish by an expert panel. We employed the back translation method for linguistic validation. Cronbach's α and test-retest analysis were performed for reliability analysis. The overactive bladder-v8 (OAB-v8) questionnaire was also administered for concurrent validation, and expanded disability status scale (EDSS) and multiple sclerosis quality of life scale-54 (MSQL-54) were used to evaluate construct validity. RESULTS: One hundred and five patients (84 females; mean age, 39.5 ± 11.6 years; mean EDSS score, 3.2 ± 1.8) participated in the study. Mean duration of MS was 9.7 ± 8.3 years, and most (n = 96; 91.5%) had relapsing-remitting MS. The mean ABSST score was 9.7 ± 5.8 (range, 0-21). Highest scores were obtained from urgency and frequency, and the lowest from psychosocial effects of lower urinary tract (LUT) symptoms. The Cronbach's α coefficient was 0.856, and item-total score correlations ranged between 0.485 and 0.845. Correlations of ABSST scores with OAB-v8, EDSS, and MSQL-54 scales were significant (P < .001). According to the questionnaire, 38.1% (n = 40) of the patients needed a referral to a urologist or gynecologist for their LUT symptoms. CONCLUSIONS: The Turkish version of the ABSST is a valid and reliable screening tool that can be used to identify LUT symptoms in an MS clinic.
Asunto(s)
Síntomas del Sistema Urinario Inferior/diagnóstico , Esclerosis Múltiple/complicaciones , Calidad de Vida , Vejiga Urinaria Hiperactiva/diagnóstico , Adulto , Femenino , Humanos , Síntomas del Sistema Urinario Inferior/etiología , Síntomas del Sistema Urinario Inferior/fisiopatología , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/fisiopatología , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Traducciones , Vejiga Urinaria Hiperactiva/etiología , Vejiga Urinaria Hiperactiva/fisiopatologíaRESUMEN
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a heritable, rare small vessel disease, which is caused by HTRA1 mutations and mostly reported Japanese and Chinese population. CARASIL is an orphan disease, which presents with progressive motor and cognitive impairment, alopecia, and spondylosis. The disease typically starts with lumbago at early twenties. Ischemic strokes start at mid-twenties. Patients have no cardiovascular or any other risk factors. Multiple lacunar infarcts and leukoencephalopathy cause progressive neurologic involvement. Leukoencephalopathy and small vessel disease without any risk factors is a significant finding for the differential diagnosis of HTRA1 gene pathology. This report presents clinical and genetic features of a rare case of typical CARASIL from Turkey who was followed with uncertain diagnoses for years.
Asunto(s)
Alopecia/genética , Infarto Cerebral/genética , Heterocigoto , Serina Peptidasa A1 que Requiere Temperaturas Altas/genética , Leucoencefalopatías/genética , Mutación , Enfermedades de la Columna Vertebral/genética , Adulto , Alopecia/diagnóstico por imagen , Alopecia/fisiopatología , Alopecia/psicología , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/fisiopatología , Infarto Cerebral/psicología , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Humanos , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/fisiopatología , Leucoencefalopatías/psicología , Imagen por Resonancia Magnética , Masculino , Fenotipo , Factores de Riesgo , Enfermedades de la Columna Vertebral/diagnóstico por imagen , Enfermedades de la Columna Vertebral/fisiopatología , Enfermedades de la Columna Vertebral/psicologíaRESUMEN
BACKGROUND: Patients with Behçet's disease (BD) may rarely manifest with cerebral white matter lesions resembling multiple sclerosis (MS). This may result in misdiagnosis due to diagnostic difficulties between parenchymal neuro-BD (pNBD) and MS. This study aims to elucidate the distinguishing features of patients with comorbid BD and MS (BD+MS) in comparison to those with pNBD and MS alone by focusing on clinical and laboratory features. We also aimed to identify the distinctive characteristics of BD+MS patients by comparing them to patients with pNBD and MS. METHODS: The methodology of this study involved a retrospective analysis of patient records followed in the Department of Neurology at the Istanbul Faculty of Medicine, Istanbul University. The study population included patients diagnosed with pNBD, MS, and a comorbid condition of BD and MS (BD+MS). We assessed clinical, radiological, and laboratory data, including disease onset, annual relapse rates, Expanded Disability Status Scale (EDSS) progression, and cerebrospinal fluid examination. Several parameters were examined between the pNBD, MS, and BD+MS patient groups to find similarities and differences between subgroups. RESULTS: Our study included 1,764 patients: 172 with pNBD, 1,574 with MS, and 18 with BD+MS. A predominance of females was noted in the BD+MS (72%, p < 0.001) and MS (69 %, p < 0.001) groups compared to pNBD (30 %). The median age at the onset of neurological symptoms was 35.5 (IQR: 16.8) years for BD+MS, 34.6 (13.6) years for pNBD, and 27.6 (13.3) years for MS (BD+MS vs. MS; p = 0.3, pNBD vs. MS, p = 0.7). Additionally, the number of attacks was notably different, with BD+MS patients experiencing a median of 3.5 (2.0) attacks compared to 3.0 (3.0) for MS patients and only 1.0 (1.0) for pNBD patients, suggesting a more active disease course in the MS and BD+MS groups compared to pNBD (p < 0.001). The median annualized relapse rate for BD+MS was 0.3 (0.2), which was lower than the rate of 0.4 (0.4) in MS (p = 0.048) and equivalent to the rate of 0.2 (0.3) in pNBD (p = 0.2). The time to the first relapse was similar to those with BD+MS and MS, but considerably shorter than in individuals with pNBD (p < 0.0001). The cerebrospinal fluid (CSF) analysis showed no significant differences in neutrophil and lymphocyte counts between BD+MS and MS patients but elevated levels in pNBD patients (p < 0.05). CSF protein levels were consistent across all groups (p = 0.1 and p = 0.7). Oligoclonal bands were detected in all patients with BD+MS, in the majority of MS patients (83.6 %), and a small percentage of pNBD patients (19.7 %), showing a notable distinction between the BD+MS and pNBD groups (p < 0.001). CONCLUSION: Our study underscores the need for a skeptical approach in diagnosing and treating patients with BD who exhibit symptomatic MS-like MRI lesions. Our findings suggest that BD+MS is a distinct clinical entity, warranting specific diagnostic and treatment approaches. Our findings highlight that BD patients with MS-like lesions meeting MS diagnostic criteria should be managed as patients with comorbid MS and BD rather than pNBD.
Asunto(s)
Síndrome de Behçet , Esclerosis Múltiple , Humanos , Síndrome de Behçet/complicaciones , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/fisiopatología , Femenino , Masculino , Adulto , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico por imagen , Estudios Retrospectivos , Comorbilidad , Persona de Mediana Edad , Imagen por Resonancia Magnética , Adulto JovenRESUMEN
BACKGROUND: We aimed to evaluate the validity and reliability of the Turkish version of the Patient-Reported Impact of Spasticity Measure (PRISM-TR). METHODS: Expert opinions and the forward-back translation method were used for linguistic validation. Cronbach α and test-retest analysis were performed for reliability analysis. Correlations between the PRISM-TR and the Modified Ashworth Scale (MAS), the Numerical Rating Scale (NRS), and the Expanded Disability Status Scale (EDSS) were assessed. RESULTS: A total of 206 individuals with multiple sclerosis (MS; 139 women; mean age, 47.7 ± 11.3 years; mean EDSS score, 5.2 ± 1.5) who had not had a relapse in the previous 3 months were included in the study. Test-retest correlation coefficients were high for all subdimensions of the scale (0.95-0.99). All Cronbach α values for the PRISM-TR subdimensions, except for Positive Impact, were likewise quite high (0.85-0.94). PRISM-TR subscale scores were correlated with MAS, NRS, and EDSS scores (P < .001). CONCLUSIONS: PRISM-TR is a valid and reliable scale for use with Turkish individuals with MS. It is simple to use in the clinic and can be helpful in detecting patients' spasticity early in the disease course.
RESUMEN
BACKGROUND: To investigate the reliability of balance tests administered using a tele-assessment method in patients with multiple sclerosis (MS). METHODS: The participants were assessed both online and face-to-face. The assessments were performed synchronously by two physiotherapists. The first method to used to evaluate the participants was determined through randomization. The Berg Balance Scale (BBS), Dynamic Gait Index (DGI), and Timed Up and Go (TUG) were used in the evaluations. Three days were left between the assessment methods. Online platforms were used for tele-assessment. The agreement between and correlation of face-to-face and tele-assessments was analyzed by applying intra-class correlation coefficients (ICC), limits of agreement, and Pearson's correlation coefficient. RESULTS: This study included 39 individuals with MS with an EDSS score of 3.03 ± 1.41. Intra-rater reliability of the tele-assessment was excellent (ICCBBS = 0.96; ICCDGI = 0.97; ICCTUG = 0.97). Very high correlations were observed in all BBS, DGI, and TUG measurements between face-to-face and tele-assessment methods according to the first and second assessors (rBBS1 = 0.92; rBBS2 = 0.93; rDGI1 = 0.94; rDGI2 = 0.95; rTUG1 = 0.94; rTUG2 = 0.95, respectively). The inter-rater reliability of tele-assessments (ICCBBS = 0.97; ICCDGI = 0.97; ICCTUG = 1.00) achieved excellent reliability. CONCLUSION: BBS, DGI, and TUG are reliable and agreed tests that can be used with tele-assessments, offering similar data to face-to-face methods.
RESUMEN
Introduction: Parenchymal Neuro-Behçet's disease (p-NBD) usually presents with a characteristic lesion in the mesodiencephalic region. However, there is a lack of information regarding the axonal integrity of normal-appearing white matter in p-NBD. Diffusion tensor imaging (DTI) is based on the properties of diffusivity and anisotropy that indicate the integrity of axons. The primary objective of the study was to compare p-NBD patients to healthy controls using diffusion tensor magnetic resonance imaging (DTI-MRI). Methods: The study enrolled parenchymal p-NBD patients who maintained stable disease status for 12 months. Healthy controls were chosen from a population with a similar age and gender distribution. Axial DTI was acquired using single-shot echo-planar imaging. Group analyses were carried out using the track-based spatial statistics tool of FMRIB software library (FSL). Correlations between DTI parameters and clinical outcomes were analyzed in the patient group. Results: We recruited 12 patients with p-NBD and 12 healthy individuals. We found significant fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) differences in the superior longitudinal fasciculus, superior corona radiata, anterior corona radiata, body and genu of the corpus callosum, external capsule, and anterior limb of the internal capsule, mainly in the frontal white matter. Conclusion: Patients with p-NBD exhibit significant DTI alterations in the otherwise normal-appearing frontal association tracts. This study may contribute to a better understanding of the neuropsychological impairment pattern in patients with p-NBD, which is often associated with frontal cognitive networks.
Asunto(s)
Encéfalo/diagnóstico por imagen , Lipodistrofia , Glicoproteínas de Membrana/genética , Mutación/genética , Osteocondrodisplasias , Receptores Inmunológicos/genética , Panencefalitis Esclerosante Subaguda , Adulto , Trastornos del Conocimiento/etiología , Femenino , Humanos , Lipodistrofia/complicaciones , Lipodistrofia/diagnóstico por imagen , Lipodistrofia/genética , Osteocondrodisplasias/complicaciones , Osteocondrodisplasias/diagnóstico por imagen , Osteocondrodisplasias/genética , Panencefalitis Esclerosante Subaguda/complicaciones , Panencefalitis Esclerosante Subaguda/diagnóstico por imagen , Panencefalitis Esclerosante Subaguda/genéticaRESUMEN
Crohn's disease is an inflammatory, autoimmune disorder that predominantly affects the intestines but can also affect extraintestinal organs. Certain neurological conditions, such as autoimmune encephalitis, can develop along with this disease. In this case report, we present a case of anti-glutamic acid decarboxylase (GAD) antibody-associated autoimmune encephalitis that occurred shortly after the diagnosis of Crohn's disease and was unrelated to the treatment and nutritional deficiencies. After a significant weight loss (24 kg) and persistent diarrhea, the patient was diagnosed with Crohn's disease by colonoscopy and biopsy. Within two weeks after the diagnosis, he experienced altered consciousness and memory impairment, followed by a rapid deterioration in consciousness and respiratory distress, leading to intubation and admission to the intensive care unit. His brain MRI revealed asymmetrical diffuse cortical diffusion restrictions, hyperintense signals on fluid-attenuated inversion recovery (FLAIR) sequences, and diffuse pachymeningeal contrast enhancement involving both cingulate gyri, bilateral insular cortices, amygdalae, hippocampi, and the right precuneus. Analysis of cerebrospinal fluid (CSF) revealed a slight elevation of CSF proteins, and the patient tested positive for serum anti-GAD antibodies. The patient responded favorably to a seven-day course of intravenous methylprednisolone, five days of intravenous immunoglobulin (IVIG), and oral corticosteroids. Subsequent treatment consisted of monthly IVIG, azathioprine, and vedolizumab, resulting in no neurologic sequelae except mild amnesia. A follow-up MRI at three months showed a nearly complete disappearance of the lesions. This is the first reported case of anti-GAD-associated encephalitis occurring in the presence of Crohn's disease.
RESUMEN
BACKGROUND: Given the significance of glial cells in maintenance of neurons, antibodies directed against glial cells of the optic nerve might reasonably be expected to have a pathogenic impact in relapsing inflammatory optic neuropathy (RION). METHODS: We investigated IgG immunoreactive with the optic nerve tissue by indirect immunohistochemistry using sera of 20 RION patients. Commercial Sox2-antibody was used for double immunolabeling. RESULTS: Serum IgG of 5 RION patients reacted with cells aligned in the interfascicular regions of the optic nerve. IgG binding sites significantly co-localized with the Sox2-antibody. CONCLUSION: Our results suggest that a subset of RION patients may harbor anti-glial antibodies.
Asunto(s)
Neuritis , Enfermedades del Nervio Óptico , Neuritis Óptica , Humanos , Nervio Óptico , Ojo , Neuroglía , Inmunoglobulina G , Factores de Transcripción SOXB1RESUMEN
AIM: Behçet's disease (BD) is a multisystemic inflammatory disease. Cerebral venous sinus thrombosis (CVST) is the second most common form of neuro-BD after parenchymal central nervous system involvement. The purpose of this study was to construct flow-void probability maps of patients with CVST with and without BD to visually illustrate the impacted cerebral venous sinuses, to compare the subgroups of patients, and investigate the effect of thrombus localization on clinical findings. METHODS: Seventeen patients with a diagnosis of BD-related CVST (CVST-BD) and 23 patients with a diagnosis of CVST related to other etiologies (CVST-O) were included. We collected data including gender, age at onset of BD and CVST, presenting symptoms, neurological findings, and the etiology. High-resolution magnetic resonance venographies obtained during CVST were used to mark and digitalize thrombosed areas. Thrombus probability and subtraction maps were created to reveal the differences between the subgroups. RESULTS: Remarkably, all patients with CVST-BD had thrombosis in the transverse sinus (TS). However, TS was affected in 73.9% of the CVST-O patients (17/17 in CVST-BD vs 17/23 in CVST-O, P = .03). Thrombosis developed mostly in the superior sagittal sinus (SSS) and TS in the CVST-O group (11/23, 47.8% and 17/23, 73.9%, respectively). The frequency of SSS thrombosis tended to be higher in the CVST-O (47.8% vs 23.5%, P = .19). CONCLUSION: Venous infarction and hemorrhage were less common in patients with CVST-BD. The only clinical symptom in most of the CSVT patients with BD was headache due to elevated intracranial pressure. TS thrombosis was more common in patients with BD.
Asunto(s)
Síndrome de Behçet , Venas Cerebrales , Trombosis de los Senos Intracraneales , Humanos , Síndrome de Behçet/complicaciones , Síndrome de Behçet/diagnóstico , Venas Cerebrales/diagnóstico por imagen , Venas Cerebrales/patología , Trombosis de los Senos Intracraneales/diagnóstico por imagen , Trombosis de los Senos Intracraneales/etiología , Cefalea , Imagen por Resonancia MagnéticaRESUMEN
INTRODUCTION: Antibodies to cell surface proteins of astrocytes have been described in chronic inflammatory demyelinating disorders (CIDD) of the central nervous system including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Our aim was to identify novel anti-astrocyte autoantibodies in relapsing remitting MS (RRMS) patients presenting predominantly with spinal cord and optic nerve attacks (MS-SCON). METHODS: Sera of 29 MS-SCON patients and 36 healthy controls were screened with indirect immunofluorescence to identify IgG reacting with human astrocyte cultures. Putative target autoantigens were investigated with immunoprecipitation (IP) and liquid chromatography-mass/mass spectrometry (LC-MS/MS) studies using cultured human astrocytes. Validation of LC-MS/MS results was carried out by IP and ELISA. RESULTS: Antibodies to astrocytic cell surface antigens were detected in 5 MS-SCON patients by immunocytochemistry. LC-MS/MS analysis identified chloride intracellular channel protein-1 (CLIC1) as the single common membrane antigen in 2 patients with MS-SCON. IP experiments performed with the commercial CLIC1 antibody confirmed CLIC1-antibody. Home made ELISA using recombinant CLIC1 protein as the target antigen identified CLIC1 antibodies in 9/29 MS-SCON and 3/15 relapsing inflammatory optic neuritis (RION) patients but in none of the 30 NMOSD patients, 36 RRMS patients with only one or no myelitis/optic neuritis attacks and 36 healthy controls. Patients with CLIC1-antibodies showed trends towards exhibiting reduced disability scores. CONCLUSION: CLIC1-antibody was identified for the first time in MS and RION patients, confirming once again anti-astrocytic autoimmunity in CIDD. CLIC1-antibody may potentially be utilized as a diagnostic biomarker for differentiation of MS from NMOSD.
RESUMEN
BACKGROUND: COVID-19 vaccines are recommended for people with multiple sclerosis (pwMS). Adequate humoral responses are obtained in pwMS receiving disease-modifying therapies (DMTs) after vaccination, with the exception of those receiving B-cell-depleting therapies and non-selective S1P modulators. However, most of the reported studies on the immunity of COVID-19 vaccinations have included mRNA vaccines, and information on inactivated virus vaccine responses, long-term protectivity, and comparative studies with mRNA vaccines are very limited. Here, we aimed to investigate the association between humoral vaccine responses and COVID-19 infection outcomes following mRNA and inactivated virus vaccines in a large national cohort of pwMS receiving DMTs. METHODS: This is a cross-sectional and prospective multicenter study on COVID-19-vaccinated pwMS. Blood samples of pwMS with or without DMTs and healthy controls were collected after two doses of inactivated virus (Sinovac) or mRNA (Pfizer-BioNTech) vaccines. PwMS were sub-grouped according to the mode of action of the DMTs that they were receiving. SARS-CoV-2 IgG titers were evaluated by chemiluminescent microparticle immunoassay. A representative sample of this study cohort was followed up for a year. COVID-19 infection status and clinical outcomes were compared between the mRNA and inactivated virus groups as well as among pwMS subgroups. RESULTS: A total of 1484 pwMS (1387 treated, 97 untreated) and 185 healthy controls were included in the analyses (male/female: 544/1125). Of those, 852 (51.05%) received BioNTech, and 817 (48.95%) received Sinovac. mRNA and inactivated virus vaccines result in similar seropositivity; however, the BioNTech vaccination group had significantly higher antibody titers (7.175±10.074) compared with the Sinovac vaccination group (823±1.774) (p<0.001). PwMS under ocrelizumab, fingolimod, and cladribine treatments had lower humoral responses compared with the healthy controls in both vaccine types. After a mean of 327±16 days, 246/704 (34.9%) of pwMS who were contacted had COVID-19 infection, among whom 83% had asymptomatic or mild disease. There was no significant difference in infection rates of COVID-19 between participants vaccinated with BioNTech or Sinovac vaccines. Furthermore, regression analyses show that no association was found regarding age, sex, Expanded Disability Status Scale score (EDSS), the number of vaccination, DMT type, or humoral antibody responses with COVID-19 infection rate and disease severity, except BMI Body mass index (BMI). CONCLUSION: mRNA and inactivated virus vaccines had similar seropositivity; however, mRNA vaccines appeared to be more effective in producing SARS-CoV-2 IgG antibodies. B-cell-depleting therapies fingolimod and cladribine were associated with attenuated antibody titer. mRNA and inactive virus vaccines had equal long-term protectivity against COVID-19 infection regardless of the antibody status.
Asunto(s)
COVID-19 , Esclerosis Múltiple , Femenino , Humanos , Masculino , Vacunas contra la COVID-19/uso terapéutico , COVID-19/prevención & control , Esclerosis Múltiple/tratamiento farmacológico , Cladribina , ARN Mensajero , Estudios Transversales , Clorhidrato de Fingolimod , Estudios Prospectivos , SARS-CoV-2 , Anticuerpos Antivirales , VacunaciónRESUMEN
Introduction: Coronavirus disease 2019 (COVID-19) is the biggest health challenge of recent times. Studies so far reveal that vaccination is the only way to prevent this pandemic. There may be factors that decrease or increase vaccine effectiveness. In multiple sclerosis (MS), some of these factors may cause changes in the effectiveness of the vaccine, depending on the nature of the disease and disease-modifying treatments (DMT). In this study, we aimed to investigate the relationship between antibody titer and smoking in non-treated and DMT-treated MS patients who received inactivated vaccine (Sinovac) and messenger RNA BNT162b2 (BioNTech) mRNA vaccines. Method: Vaccine antibody responses were measured between 4-12 weeks after two doses of inactivated vaccine and mRNA vaccines. Patients were separated into 6 groups as: patients with MS without treatment PwMS w/o T, ocrelizumab, fingolimod, interferons (interferon beta-1a and interferon beta-1b), dimethyl fumarate, and teriflunomide. Antibody titers of smokers and non-smokers were compared for both vaccines and for each group. Results: The study included 798 patients. In the mRNA vaccine group, smokers (n=148; 2982±326 AU/mL) had lower antibody titers compared to the non-smokers (n=244; 5903±545 AU/mL) in total (p=0.020). In the inactivated vaccine group, no significant difference was detected between smokers (n=136; 383±51 AU/mL) and non-smokers (n=270; 388±49 AU/mL) in total (p=0.149). In both vaccine groups, patients receiving ocrelizumab and fingolimod had lower antibody titers than those receiving other DMTs or PwMS w/o T. In untreated MS patients, antibody levels in smokers were lower than in non-smokers in the mRNA vaccine group. No difference was found between antibody levels of smokers and non-smokers in any of the inactivated vaccine groups. Conclusion: Ocrelizumab and fingolimod have lower antibody levels than PwMS w/o T or other DMTs in both mRNA and inactivated vaccine groups. Smoking decreases antibody levels in the mRNA vaccine group, while it has no effect in the inactivated vaccine group.
RESUMEN
Both multiple sclerosis (MS) and neuro-Behcet's disease (NBD) can cause a cognitive dysfunction mainly involving the executive functions. We conducted this study to clarify the probable differential cognitive/behavioral profiles of MS and NBD. Twenty consecutive cases with parenchymal NBD (13 male, seven female), and 20 cases with MS (five male, 15 female) were evaluated. Both groups had a thorough neurological examination; an evaluation for Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Beck's Depression Scale; and a detailed neuropsychological evaluation masked to the diagnosis. Among the two groups, male/female ratio differed significantly while other demographic and clinical features were not different. In California Verbal Learning Test, both short- and long-term delayed recall and cued recognition were worse in neuro-Behcet's cases. They had impaired semantic clustering and increased false positives. Stroop Test was also more impaired in neuro-Behcet's cases. They needed significantly more trials to complete the first category of the Wisconsin Card Sorting Test and had a poorer total Frontal Behavioral Inventory Score. Our results suggest that neuro-Behcet's patients have a more severe "frontal"-executive dysfunction than MS patients.
Asunto(s)
Síndrome de Behçet/complicaciones , Encéfalo/patología , Trastornos del Conocimiento/etiología , Demencia/etiología , Esclerosis Múltiple/complicaciones , Adulto , Síndrome de Behçet/patología , Síndrome de Behçet/fisiopatología , Encéfalo/fisiopatología , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/fisiopatología , Demencia/patología , Demencia/fisiopatología , Evaluación de la Discapacidad , Función Ejecutiva/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/patología , Esclerosis Múltiple/fisiopatología , Pruebas NeuropsicológicasRESUMEN
BACKGROUND AND PURPOSE: Behçet's disease (BD) is an inflammatory disorder with multisystemic involvement. The most disabling aspect of BD is Neuro-Behçet's disease (NBD). In NBD, parenchymal lesions tend to occur in the mesodiencephalic region and brainstem, as reported in large series of NBD. Our study aimed to generate probability maps of parenchymal lesions to compare patient subgroups with different clinical and laboratory features. METHOD: We included 66 non-standardized acute relapse MRIs of 55 patients with parenchymal NBD (p-NBD). We used T2-weighted axial images to digitalize the lesions using the CAD software. Boundaries of lesions were determined as polygons and converted into high-definition raster datasets. Then, digitalized lesion maps were transferred into the ICBM-152 brain template to perform spatial analyses. Finally, we created subtraction maps to compare the patient subgroups. RESULTS: We used a total of 66 MRIs of 55 patients to generate the probability maps. The most frequently affected parenchymal structures were the rostral pons, mesencephalon, and diencephalic region. Interestingly, the brainstem was more commonly affected in females than males (p<0.01). In the late-onset disease, lesions were localized in the corticospinal tracts and caudal brainstem (p<0.01). Progressive disease and severe disability at the end of the follow-up period were associated with corticospinal tract lesions during relapses (p<0.01). Patients with positive pathergy tests were more likely to present right hemisphere involvement (p<0.01). Additionally, cyclosporine-induced lesions tend to be in atypical locations such as hemispheric white matter. CONCLUSIONS: In the published studies, lesions in NBD were localized according to coarse anatomical regions. Our study uses visual maps to offer accurate lesion localizations using non-standardized brain MRIs, allowing comparisons across different NBD subgroups. By using this technique, we investigated the relationship of the clinical and laboratory features with the lesion locations. We found that the late age of onset was associated with a poor prognosis. Additionally, corticospinal lesions may predict severe and progressive disease course, requiring aggressive treatment. Interestingly, females had more brainstem lesions and lesion lateralization might be influenced by the pathergy test status.