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CLINICAL RATIONALE FOR THE STUDY: The rapid spread of SARS-CoV-2 throughout the world has highlighted the importance of vaccinations to control the pandemic and to protect people at risk for severe disease courses. Disease-modifying therapies (DMT) in multiple sclerosis (MS), whether immunomodulatory or immunosuppressive, may affect the immune response. Therefore, the question arose as to whether these vaccinations would be effective. AIM OF THE STUDY: We planned a study to assess the immune response to SARS-CoV-2 vaccines by type of therapy. MATERIAL AND METHODS: Participants were recruited from 14 Polish MS centres. The data was obtained by neurologists using a questionnaire. We collected data on 353 MS patients (269 females, 84 males) who received complete primary SARS-CoV-2 vaccination. All persons with MS (PwMS) were treated with disease-modifying therapies. RESULTS: 305 out of 353 PwMS (86.4%) were positive for IgG Abs against SARS-CoV-2 S domain S1 Ag after vaccination. A strong immune response was noted in 129 PwMS (36.5%). The rate of seroconversion after SARS-CoV-2 vaccination in PwMS who received immunomodulatory DMTs (interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab) was 91.5%, in PwMS receiving immune reconstruction therapy (alemtuzumab, cladribine) was 92%, and in immunosuppressive DMTs (fingolimod, ocrelizumab), the seroconversion rate was 59%. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study shows that, in PwMS receiving immunomodulatory therapy, the immune response to vaccination is generally excellent. Even in immunosuppressive patients, seroconversion is satisfactory.
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COVID-19 , Esclerosis Múltiple , Femenino , Masculino , Humanos , Esclerosis Múltiple/tratamiento farmacológico , Polonia , Vacunas contra la COVID-19 , Seroconversión , COVID-19/prevención & control , SARS-CoV-2 , Inmunosupresores/uso terapéuticoRESUMEN
INTRODUCTION: Multiple sclerosis (MS) is one of the most common autoimmune diseases worldwide, and various autoimmune comorbidities have been reported with MS. The aim of this study was to estimate the prevalence of autoimmune disease comorbidity in patients with MS and their relatives in a Polish population. MATERIAL AND METHODS: In this retrospective multicentre study, we investigated a group of patients with MS, and their relatives, in terms of age, gender, and the presence of simultaneous autoimmune diseases such as Graves's Disease, Hashimoto's thyroiditis, type 1 diabetes mellitus, myasthenia gravis, psoriasis, ulcerative enteritis, Crohn's Disease, coeliac disease, rheumatoid arthritis, autoimmune hepatitis and systemic lupus erythematous. RESULTS: This study included 381 patients with MS, of whom 52.23% were women. 27 patients (7.09%) had at least one autoimmune disease. The most common comorbidity was Hashimoto's thyroiditis (14 patients). 77 patients (21.45%) had relatives with an autoimmune disease, of which the most common was Hashimoto's thyroiditis. CONCLUSIONS: Our study revealed that the probability of autoimmune diseases co-occurring in patients with MS, and in their relatives, is higher and we found the greatest risk to be for Hashimoto's thyroiditis.
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Esclerosis Múltiple , Miastenia Gravis , Tiroiditis , Humanos , Femenino , Masculino , Esclerosis Múltiple/epidemiología , Estudios de Casos y Controles , Comorbilidad , Tiroiditis/epidemiologíaRESUMEN
CLINICAL RATIONALE FOR THE STUDY: The course of COVID-19 in people with multiple sclerosis (PwMS) has been described, while the serological status after SARS-CoV-2 infection or vaccination, especially in patients treated with disease-modifying therapies (DMT), is still under investigation. This is a significant clinical problem, as certain DMTs may predispose to a severe course of viral infections. AIM OF THE STUDY: We analyzed the presence of antibodies against spike (S) and nucleocapsid (N) proteins of SARS-CoV-2 in relapsing-remitting PwMS treated with DMT, especially dimethyl fumarate, interferon beta, and glatiramer acetate, in a single multiple sclerosis (MS) centre in north-eastern Poland (the Department of Neurology, Medical University of Bialystok). MATERIAL AND METHODS: The presence of antibodies against S and N proteins in PwMS was assessed twice: on visit one (between May and June 2020) (n = 186) and on visit two (between May and June 2021) (n = 88). Samples were taken from 68 individuals on both visits. Demographic and clinical data was collected: duration of MS, Expanded Disability Status Scale Score (EDSS), type of DMT, history of COVID-19 (positive PCR or antigen test in the past), vaccination status, and the type of vaccine. RESULTS: It was shown that on visit one: 3.7% (n = 7) PwMS were positive for IgA against S protein (IgA-S), 3.2% (n = 6) for IgG against S (IgG-S) protein, and none of those examined was positive for IgG against N protein (IgG-N). On visit two, the most common detected antibodies were IgG-S (71.3%; n = 62), then IgA-S (65.1%; n = 55), and the least common was IgG-N (18.2%; n = 16). On visit two: 20.45% of PwMS had a history of a positive SARS-CoV-2 PCR or antigen test during the last year. By the time of visit two, 42.05% (n = 37) of patients who participated in visit two had been full-course vaccinated against COVID-19. It was demonstrated that vaccination against SARS-CoV-2 significantly induces the production of IgG-S and IgA-S (p < 0.0001), while no difference between vaccinated and unvaccinated patients was shown in the detection of IgG-N. There was no correlation between COVID-19 infection and antibodies against proteins S and N in the study group. Moreover, the presented study did not show any relationship between the ability to produce antibodies against the S protein with any of the used DMTs. CONCLUSIONS AND CLINICAL IMPLICATIONS: According to our study, PwMS treated with dimethyl fumarate, interferon beta, or glatiramer acetate can efficiently produce antibodies against SARS-CoV-2 both after infection and after vaccination.
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COVID-19 , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , SARS-CoV-2 , Acetato de Glatiramer/uso terapéutico , Dimetilfumarato/uso terapéutico , Interferón beta , N,N-Dimetiltriptamina , Inmunoglobulina A , Inmunoglobulina G , Anticuerpos AntiviralesRESUMEN
INTRODUCTION: Happiness is crucial to patient well-being and their acceptance of their disease. The aim of this study was to assess the sense of happiness in persons with multiple sclerosis (PwMS), compare it to the level of happiness in patients with other neurological conditions, and determine which factors affect the sense of happiness in PwMS. MATERIAL AND METHODS: Five hundred and eighty-nine PwMS and 145 control subjects (post-stroke patients with chronic pain syndromes and neuropathies) were included in the study. Due to the differences between the groups in terms of demographic variables, an adjusted group of PwMS (n = 145) was selected from the entire group of PwMS. All patients were assessed using the Oxford Happiness Questionnaire (OHQ), the Satisfaction with Life Scale (SLS), and the Family APGAR Questionnaire. Based on regression analysis, the study examined which variables affected the level of happiness in the groups. RESULTS: Analysis of the OHQ scores showed that PwMS had a lower sense of happiness compared to the control group in the overall score [113.21 (25-42) vs. 119.88 (25-49), respectively; p = 0.031] and the subscales (OHQ subscale 1 - 54.52 vs. 57.84, respectively; p = 0.027; subscale 2 - 35.61 vs. 37.67; respectively; p = 0.044). Based on linear regression analysis, life satisfaction (ß = 0.40; p < 0.001), positive orientation (ß = 0.32; p < 0.001), and primary education (ß = 0.08; p = 0.009) were the most significant predictors of a higher level of happiness in PwMS. Similar results were found in the control group. CONCLUSIONS: The sense of happiness in PwMS was lower than in patients with other conditions. The most important factors influencing happiness included life satisfaction and positive orientation. Influencing these predictors should be the aim of psychological interventions, especially in patients with a reduced sense of happiness.
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Felicidad , Esclerosis Múltiple , Humanos , Polonia , Encuestas y CuestionariosRESUMEN
INTRODUCTION: The aim of this study was to report the course and outcome of SARS-CoV-2 infection in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs) in Poland. A major concern for neurologists worldwide is the course and outcome of SARS-CoV-2 infection in patients with MS treated with different DMTs. Although initial studies do not suggest an unfavourable course of infection in this group of patients, the data is limited. MATERIALS AND METHODS: This study included 396 MS patients treated with DMTs and confirmed SARS-CoV-2 infection from 28 Polish MS centres. Information concerning patient demographics, comorbidities, clinical course of MS, current DMT use, as well as symptoms of SARS-CoV-2 infection, need for pharmacotherapy, oxygen therapy, and/or hospitalisation, and short-term outcomes was collected up to 30 January 2021. Additional data about COVID-19 cases in the general population in Poland was obtained from official reports of the Polish Ministry of Health. RESULTS: There were 114 males (28.8%) and 282 females (71.2%). The median age was 39 years (IQR 13). The great majority of patients with MS exhibited relapsing-remitting course (372 patients; 93.9%). The median EDSS was 2 (SD 1.38), and the mean disease duration was 8.95 (IQR 8) years. Most of the MS patients were treated with dimethyl fumarate (164; 41.41%). Other DMTs were less frequently used: interferon beta (82; 20.70%), glatiramer acetate (42; 10.60%), natalizumab (35;8.84%), teriflunomide (25; 6.31%), ocrelizumab (20; 5.05%), fingolimod (16; 4.04), cladribine (5; 1.26%), mitoxantrone (3; 0.76%), ozanimod (3; 0.76%), and alemtuzumab (1; 0.25%). The overall hospitalisation rate due to COVID-19 in the cohort was 6.81% (27 patients). Only one patient (0.3%) died due to SARS-CoV-2 infection, and three (0.76%) patients were treated with mechanical ventilation; 106 (26.8%) patients had at least one comorbid condition. There were no significant differences in the severity of SARS-CoV-2 infection regarding patient age, duration of the disease, degree of disability (EDSS), lymphocyte count, or type of DMT used. CONCLUSIONS AND CLINICAL IMPLICATIONS: Most MS patients included in this study had a favourable course of SARS-CoV-2 infection. The hospitalisation rate and the mortality rate were not higher in the MS cohort compared to the general Polish population. Continued multicentre data collection is needed to increase the understanding of SARS-CoV-2 infection impact on the course of MS in patients treated with DMTs.
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COVID-19 , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Adulto , Femenino , Humanos , Factores Inmunológicos , Inmunosupresores , Masculino , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/epidemiología , Polonia/epidemiología , SARS-CoV-2RESUMEN
INTRODUCTION: Presence of anti-JC-virus antibodies (JCVAbs) is associated with the increased risk of natalizumab (NAT)-related progressive multifocal leukoencephalopathy (PML). Little is known about seroconversion rate and time to seroconversion in relapsing-remitting multiple sclerosis (RRMS) patients treated with NAT in Poland. The aim of the study was to assess the true risk of PML, seroconversion rate, and time to seroconversion in all JCVAb-negative RRMS patients treated with NAT in Poland. METHODS: Demographic and clinical data of all Polish RRMS patients treated with NAT reimbursed by National Health Fund (NFZ) were prospectively collected in electronic files using the Therapeutic Programme Monitoring System provided by NFZ. The assessment of JCVAb presence (without collection of JCVAb index value) in serum (Unilabs, STRATIFY JCV: anti-JCV antibody ELISA) was done at the beginning of therapy and then repeated every 6 months. The maximum follow-up time was 4 years. In Poland, since 2013, according to the NFZ drug program guidance, only patients with negative JCVAb test have started treatment with NAT. RESULTS: In all Polish multiple sclerosis centers, 210 negative JCVAb RRMS patients with at least 9 (±3) months of observation (146 females, 64 males, and the median age at baseline: 33 years) were included in the study. During the follow-up period, JCVAb status changed from negative to positive in 34 patients (16.2%). For half of the patients, the seroconversion was diagnosed 1 year after starting NAT treatment. In 4 patients (1.9%) during follow-up, JCVAb status changed again from positive to negative. In Poland, before establishment of NFZ drug program, 4 cases of PML in patients treated with NAT in clinical trials were diagnosed. In the NFZ drug program, since 2013, no patient treated with NAT has been diagnosed with PML. CONCLUSIONS: NAT therapy in JCV-seronegative RRMS patients is safe and results in the absence of PML cases. In Poland, JCV seroconversion rate is similar to that observed in other European countries.
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Factores Inmunológicos/efectos adversos , Leucoencefalopatía Multifocal Progresiva/inmunología , Esclerosis Múltiple Recurrente-Remitente/virología , Natalizumab/efectos adversos , Seroconversión , Adulto , Anticuerpos Antivirales/sangre , Femenino , Humanos , Huésped Inmunocomprometido/inmunología , Virus JC/inmunología , Leucoencefalopatía Multifocal Progresiva/epidemiología , Masculino , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Polonia , Adulto JovenRESUMEN
AIM OF STUDY: The aim of this study was to collect and analyse data on relapsing-remitting multiple sclerosis (RRMS) patients receiving disease-modifying therapies (DMTs) in Poland. MATERIAL AND METHODS: This observational, multicentre study with prospective data collection included RRMS patients receiving DMTs reimbursed by the National Health Fund (NFZ) in Poland, monitored by the Therapeutic Programme Monitoring System (SMPT). Demographic profiles, disability status, and treatment modalities were analysed. RESULTS: Data from 11,632 RRMS patients was collected (from 15,368 new prescriptions), including 10,649 patients in the first-line and 983 in the second-line therapeutic programme of DMTs. The proportion of females to males was 2.39 in the first-line and 1.91 in the second-line. The mean age at DMTs start was 36.6 years in the first-line and 35.1 in the second-line. The median time from the first symptoms to MS diagnosis was 7.4 months, and from MS diagnosis to treatment it was 18.48 months. A total of 43.4% of MS patients started DMT during the 12 months following diagnosis. There was a positive correlation between the duration from MS diagnosis to the start of DMT and a higher initial EDSS value [correlation 0.296 (p < 0.001)]. About 10% of patients stopped DMTs. In Poland, about one third of all MS patients are treated in both lines, and the choice of first-line treatment depends on the region of the country. CONCLUSIONS: In Poland there is a need to increase MS patient access to DMTs by improving the organisation of drug programmes.
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Esclerosis Múltiple , Adulto , Femenino , Humanos , Masculino , Polonia , Estudios ProspectivosRESUMEN
BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic inflammatory, autoimmune disease with a still unknown aetiology. The main initial mechanism of demyelination and injury to the central nervous system (CNS) appears to be inflammation. Neurotoxicity induced by homocysteine (Hcy) may be a factor affecting this process. 5,10-methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme involved in Hcy metabolism. It leads to Hcy remethylation to methionine. In the present study, we aimed to investigate a possible association between two variants of MTHFR gene in patients with MS in Poland and healthy individuals. METHODS: In this study, we genotyped 174 relapsing-remitting MS patients and 186 healthy controls using the TaqMan technique. RESULTS AND CONCLUSIONS: It was found that, regardless of the presence of a specific allele, the gender of MS patients affects age at the time of the clinical onset of the disease: in rs1801133 for the C allele and T, the average age was 35 years for women and 29 for men (p = 0.0004; p = 0.034 respectively). Similarly for the second polymorphism rs1801131 for the A allele and C, the average age was 35 years for women and 29 for men (p = 0.001; p = 0.01 respectively). No significant allelic / genotypic frequency differences have been observed between the studied groups (c.677C > T, CT/TT p = 0.719, p = 0.262; c.1298A > C, AC/CC of p = 0.686; p = 0.66). We found no association between polymorphisms of a folate-homocysteine-methionine-SAM metabolising gene enzyme and multiple sclerosis in a Polish population.
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Esclerosis Múltiple , Adulto , Femenino , Ácido Fólico , Frecuencia de los Genes , Genotipo , Homocisteína , Humanos , Masculino , Metionina , Metilenotetrahidrofolato Reductasa (NADPH2) , PoloniaRESUMEN
BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that leads to inflammation, demyelination and neurodegeneration. Viral aetiology has been suspected to be an MS trigger for a long time, and herpesviruses (HSs) are among the potential pathogens involved. OBJECTIVES: The present investigation aims to detect the presence of antibodies against the herpes simplex virus (HSV), varicella-zoster virus, Epstein-Barr virus (EBV), human cytomegalovirus (CMV) and human herpesvirus 6 (HHV6) in the serum of MS patients and control individuals in north-eastern Poland. METHOD: Plasma was collected from 141 MS patients and 44 blood donors who served as the control group. These individuals were assessed for the presence of antibodies using an enzyme-linked immunosorbent assay. RESULTS: The statistical analysis showed a higher probability of EBV (p = 0.037, OR 4.359) and HHV6 (p = 0.020, OR 3.343) antibody presence in patients with MS compared to that in the control group. In the MS patient group, the prevalence of CMV IgG antibodies was significantly higher in females (p = 0.025). Patients who tested positive for anti-EBV IgG were diagnosed 7.9 years earlier than patients who tested negative for anti-EBV IgG (p = 0.048). CONCLUSIONS: The study showed that MS patients in north-eastern Poland were more likely to be seropositive for EBV and HHV6 than healthy individuals. Further work should be undertaken in other regions of Poland and other European countries with particular attention paid to testing seropositivity in all HSs, particularly in the MS patient population, to evaluate the impact of HSs on MS patients in different environments.
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Infecciones por Herpesviridae/epidemiología , Esclerosis Múltiple Recurrente-Remitente/virología , Adulto , Anticuerpos Antivirales/sangre , Europa (Continente) , Femenino , Herpesviridae , Humanos , Masculino , Persona de Mediana Edad , Polonia , Adulto JovenRESUMEN
A 41-year-old female with history of Graves' disease, bilateral cataract, paroxysmal atrial fibrillation was admitted because of muscle weakness, daytime sleepiness, fatigability, drowsiness, bilateral eyelid ptosis, descending of head and lower jaw. On neurological examination the patient was presented with muscle weakness, muscle atrophy (in face and sternocleidomastoid muscles), features of myotonia and apocamnosis (orbicular muscles). Electromyography revealed myopathic changes, myotonic and pseudomyotonic discharges, positive repetitive nerve stimulation test in proximal muscles. Myotonic dystrophy (MD) diagnosis was confirmed by genetic testing and myasthenia gravis (MG) by a positive titer of cholinergic receptor autoantibodies. In the CSF concentration of hypocretin was significantly decreased.
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Trastornos de Somnolencia Excesiva/diagnóstico , Enfermedad de Graves/diagnóstico , Miastenia Gravis/diagnóstico , Distrofia Miotónica/diagnóstico , Adolescente , Adulto , Autoanticuerpos/sangre , Comorbilidad , Trastornos de Somnolencia Excesiva/genética , Electromiografía , Femenino , Pruebas Genéticas , Enfermedad de Graves/genética , Humanos , Masculino , Debilidad Muscular/diagnóstico , Miastenia Gravis/genética , Distrofia Miotónica/genética , Examen Neurológico , Receptores Colinérgicos/inmunologíaRESUMEN
BACKGROUND: Comprehensive epidemiologic data for multiple sclerosis (MS) in Poland are limited. The aim of this cross-sectional population-based study was to determine the incidence and prevalence of MS in the Swietokrzyskie Region (central Poland). METHODS: This study identified MS cases every year between 1 January 2010 and 31 December 2014. The study area population on the prevalence day (December 31, 2014) was 1,263,176 (646,506 women and 616,670 men). A total of 1462 patients with a clinically definite diagnosis of MS according to McDonald's criteria (2005), recorded in the Polish Multiple Sclerosis Registry, were considered for estimation of crude, age- and sex-specific prevalence, and incidence. RESULTS: The overall crude prevalence rate of confirmed MS patients was 115.7/100,000 (95 % confidence interval (CI), 111.2-121.4). A significantly higher prevalence was recorded in females (159.6/100,000; 95 % CI, 151.1-165.3) than in males (69.7/100,000; 95 % CI, 62.4-77.3) (P < 0.001). Age-adjusted rates for the Polish and European Standard Population were 109.8/100,000 (95 % CI, 105.4-114.8) and 106.6/100,000 (95 % CI, 101.1-111.2), respectively. The female/male ratio was 2.4. The mean annual incidence was 4.2/100,000 (95 % CI. 3.7-4.4). CONCLUSION: The incidence and prevalence of MS in the Swietokrzyskie region confirm that central Poland is a high risk area for MS. Compared with previous epidemiologic studies from Poland, the prevalence of MS has increased during recent years.
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Esclerosis Múltiple/epidemiología , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Polonia/epidemiología , PrevalenciaRESUMEN
BACKGROUND/AIMS: We evaluated renal function and the impact of renal function on in-hospital outcomes in patients with ischaemic and haemorrhagic stroke. METHODS: We collected data from 766 patients with stroke; 637 (83.2 %) with ischaemic and 129 with haemorrhagic one. RESULTS: The mean serum creatinine on admission in patients with both types of stroke, who died, was significantly higher than in those who survived. Multivariate analysis showed that independent predictors of mortality in patients with ischaemic stroke were: ischemic heart disease or prior myocardial infarction, diabetes, admission glucose and eGFR on admission. Also, multivariate analysis showed that independent predictors of mortality in patients with haemorrhagic stroke were: age and admission glucose. CONCLUSIONS: Patients with haemorrhagic stroke, in particular with acute kidney injury during hospitalisation had significantly worse outcomes than patients with ischaemic stroke. Assessment of kidney function is prerequisite to employ the necessary measures to decrease the risk of in-hospital mortality among patients with acute stroke. Appropriate approach to patients with renal dysfunction (adequate hydration, avoidance of nephrotoxic drugs, drug dose adjustment etc) should be considered as preventive and therapeutic strategies in the management of acute stroke.
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Isquemia Encefálica/mortalidad , Hemorragia Cerebral/mortalidad , Accidente Cerebrovascular/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Manejo de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Enfermedades Renales/diagnóstico , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/prevención & control , Resultado del TratamientoRESUMEN
Xanthomatosis is a genetic disease inherited in an autosomal recessive manner. The specific phenotypic features are associated with patient's genetic profile. The result of the mutation is disorder of cholesterol synthesis and the accumulation of its precursors in tissues. The characteristic symptoms are progressive cerebellar ataxia, cataract, diarrhea, and the deposition of cholesterol in the tendons. Our objective is to follow-up information to treatment efficacy of 22-year-old patient diagnosed with cerebrotendinous xanthomatosis through 1.5 year observation. In 2012, an 11-year-old patient with a long history of deformed feet and frequent yellowing of the skin, was admitted to the Department of Neurology due to seizures. In 2013, the patient began to suffer from diarrhea, and its frequency was correlated with the concentration of bilirubin in the blood. In the same year cataract was diagnosed. Gradually, the patient starts to complain about progressive difficulties in moving. In 2019, genetic tests confirmed the diagnosis of cerebrotendinous xanthomatosis. Since July 2021, the patient has been treated with chenodeoxycholic acid. The deterioration of patient's mobility has been significantly inhibited, consequently his quality of life has improved. The presented case report underscores the efficacy of CDCA supplementation in halting the progression of CTX, resulting in marked improvements in the patient's quality of life.
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The coronavirus 2019 disease (COVID-19) course and serological statuses of patients with relapsing-remitting multiple sclerosis (RRMS), treated with disease-modifying therapies (DMTs) are generally parallel that of the general population. Over the pandemic's course, however, a notable increase in the number of RRMS patients who received vaccination against severe acute respiratory coronavirus 2 (SARS-CoV-2) and those who had COVID-19 (symptomatic and asymptomatic) was reported. This virus and/or vaccination likely influenced DMT-treated RRMS patients' serological statuses regarding the presence of SARS-CoV-2 antibodies and their quantitative expression. This investigation assesses the presence and levels of the antibody directed against the S1 protein receptor binding domain (SRBD) and against the N protein of SARS-CoV-2 in 38 DMT-treated RRMS patients. The findings indicate that people vaccinated against SARS-CoV-2 exhibited significantly higher levels of IgG antibodies against S1-RBD at both assessment points. Patients with a prior history of COVID-19 demonstrated statistically significant increases in anti-N antibodies at visit 1, whereas such statistical significance was not observed at visit 2. DMT-treated RRMS patients generated neutralizing antibodies following vaccination and/or COVID-19 infection. Nevertheless, it is noteworthy that antibody levels more accurately reflect the serological status and exhibit a stronger correlation with vaccination than just the presence of antibodies.
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Andexanet alfa (AA) is a recombinant inactive analog of human activated factor X (FXa), effectively reversing the effects of its inhibitors - rivaroxaban and apixaban, which are available in Poland. The drug was approved for clinical use registration after the publication of the results of the ANNEXA-4 trial (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXa Inhibitors 4), in which its efficacy in restoring hemostasis in life-threatening hemorrhages in patients receiving using the aforementioned anticoagulants was demonstrated. Hence, AA is now recommended for patients on apixaban or rivaroxaban therapy with massive and uncontrollable hemorrhages, including hemorrhagic strokes (HS) and gastrointestinal bleeding. Drug-specific chromogenic anti-Xa assays are generally best suited for estimating rivaroxaban and apixaban plasma levels, aside from direct assessment of their concentrations. The absence of anti-Xa activity, determined using these assays, allows us to rule out the presence of clinically relevant plasma concentrations of any FXa inhibitor. On the other hand, the dose of AA should not be modified based on the results of coagulation tests, as it depends solely on the time that elapsed since the last dose of FXa inhibitor and oon the dose and type of FXa inhibitor. AA is administered as an intravenous (i.v.) bolus, followed by an i.v. infusion of the drug. The maximum reversal of anti-Xa activity occurs within two minutes of the end of the bolus treatment, with the continuation of the continuous i.v. infusion allowing the effect to be maintained for up to two hours afterwards. Because anticoagulant activity can reappear after the infusion is completed, it is currently unclear at what point after AA administration FXa inhibitors or heparin should be re-administered. In Poland AA is starting to become available and its urgent need to administer it to patients with severe bleeding on apixaban or rivaroxaban.
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Factor Xa , Rivaroxabán , Humanos , Rivaroxabán/uso terapéutico , Factor Xa/uso terapéutico , Polonia , Inhibidores del Factor Xa/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Proteínas Recombinantes/uso terapéutico , Anticoagulantes/uso terapéuticoRESUMEN
Intrathecal synthesis of the antibodies specific to neurotrofic viruses: measles (M), rubella (R), Varicella-Zoster (Z), and/or H. simplex (H), known as "MRZH-reaction" plays important diagnostic role in multiple sclerosis (MS). Whereas the analysis of the oligoclonal IgG bands provides high sensitivity, the MRZH-reaction shows high specificity, and hence these methods complement each other. For the first time we applied multiplexing bead-based technology to simultaneously analyze cerebrospinal fluid (CSF) and serum concentrations of antibodies against these viruses, and to calculate the antibody specific indices (ASI's). The method shows reasonable precision: intra-assay, 2.9-6.7%, and inter-assay, 2.0-3.2%. The results are comparable with these obtained with other methods (ELISAs), including two runs of the certified external quality control schemes. Eighty-one percent of the MS cases (n=27) and none of the sex- and age-matched controls (n=14), except one subject with "borderline" anti-measles ASI of 1.5, showed intrathecal synthesis of IgG against at least one of the viruses discussed. The ratios of the MRZH-positive cases in the MS group were: 12/22 for M, 12/19 for R, 13/26 for Z, and 7/26 for H. We conclude that the multiplexing technology can be applied as a tool to study the intrathecal immune response in the diagnosis of MS.
Asunto(s)
Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/líquido cefalorraquídeo , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/metabolismo , Adulto , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Femenino , Herpesvirus Humano 3/inmunología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/líquido cefalorraquídeo , Técnicas de Inmunoadsorción/normas , Masculino , Virus del Sarampión/inmunología , Microesferas , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/virología , Control de Calidad , Juego de Reactivos para Diagnóstico/normas , Reproducibilidad de los Resultados , Virus de la Rubéola/inmunología , Simplexvirus/inmunología , Programas Informáticos , Adulto JovenRESUMEN
Variants in the ERCC4 gene have been described to be associated with the following autosomal recessive diseases: xeroderma pigmentosum group F (XPF), xeroderma pigmentosum type F/Cockayne syndrome (XPF/CS), Fanconi anemia complementation group Q (FANCQ), and XFE progeroid syndrome (XFEPS). In this paper, we present a case of a 53-year-old Caucasian female patient with rare variants in the ERCC4 gene. When she was 42 years old, falls and loss of balance occurred. At the age of 48, involuntary, uncoordinated movements of the upper limbs and head, tongue stereotypes (licking and extending movements), speech problems (dysarthria), memory deterioration, and hearing loss occurred. Since childhood, she has shown hypersensitivity to UV radiation. The neurological examination revealed chorea syndrome, cerebellar ataxia, dysarthria, and bilateral hearing loss. She has numerous pigmented lesions on the skin. Brain MRI demonstrated massive cortico-subcortical atrophy. The neuropsychological examination revealed dysfunctions in the executive domain in terms of attention, working memory, organizing, and planning activities. The genetic diagnostics was performed which excluded spinocerebellar ataxia types 1, 2, 3, 6, and 17, Huntington's disease, and FMR1 premutation. In the genetic analysis of next-generation sequencing (NGS), two variants: c.2395C > T and c.1349G > A in the ERCC4 gene were identified in a heterozygote configuration. So far, a few cases of ERCC4 gene variants, which are associated with nucleotide excision repair pathways, have been described in connection with symptoms of cerebellar ataxia. In patients with ERCC4 biallelic variants, the adult neurological phenotype can sometimes be the first symptom and reason for access to genetic testing. The aforementioned case highlights the occurrence of rare genetic causes of progressive neurodegenerative diseases in adults, especially with the spectrum of autosomal recessive nucleotide excision repair pathway disorders (NERDs).
RESUMEN
There are several case reports describing a temporal correlation between the first clinical manifestation of multiple sclerosis (MS) and the occurrence of relapses with vaccination against SARS-CoV-2. Here we report a case of a 33-year-old male who developed partial right upper and lower extremities numbness 2 weeks after receiving Johnson & Johnson's Janssen COVID-19 vaccine. The brain MRI performed during diagnostics in the Department of Neurology detected several demyelinating lesions, one with enhancement. Oligoclonal bands were present in the cerebrospinal fluid. The patient was treated with high-dose glucocorticoid therapy with improvement and the diagnosis of MS was made. It seems plausible that the vaccination revealed the underlying autoimmune condition. Cases like the one we reported here are rare, and-based on current knowledge-the benefits of vaccination against SARS-CoV-2 far outweigh the potential risks.