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1.
Neuroepidemiology ; 57(1): 1-6, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36366822

RESUMO

BACKGROUND: Guillain-Barré syndrome is an immune-mediated acute inflammatory polyneuropathy that is associated with various triggers, including certain infections and vaccines. It has been suggested that both SARS-CoV-2 infection and vaccination may be triggering factors for Guillain-Barré syndrome, but evidence remains equivocal. Here, we conducted a population-based incidence study of Guillain-Barré syndrome spanning the 3 years immediately prior to and the 2 years during the pandemic. METHODS: Cases were identified by searching a regional diagnostic database for the ICD-10 code for Guillain-Barré syndrome. Individuals who fulfilled the Brighton criteria for Guillain-Barré syndrome were included. Information on clinical presentation, laboratory values, and vaccination status were retrieved from medical records. We calculated the incidence immediately prior to and during the pandemic. RESULTS: The Guillain-Barré syndrome incidence rate was 1.35/100,000 person-years for the pre-pandemic period and 0.66/100,000 person-years for the pandemic period (incidence rate ratio: 0.49; p = 0.003). Three cases were temporally associated with SARS-CoV-2 infection and 1 case each to the AstraZeneca and Pfizer-BioNTech COVID-19 vaccines. CONCLUSIONS: Our results show that the incidence of Guillain-Barré syndrome decreased during the pandemic. This is most likely due to decreased prevalence of triggering infections due to social restrictions. Our findings do not support a causal relationship between Guillain-Barré syndrome and COVID-19.


Assuntos
COVID-19 , Síndrome de Guillain-Barré , Vacinas contra Influenza , Humanos , Síndrome de Guillain-Barré/epidemiologia , Estudos Retrospectivos , Incidência , Pandemias , Vacinas contra COVID-19 , COVID-19/epidemiologia , COVID-19/complicações , SARS-CoV-2
2.
Epilepsia ; 64(10): 2690-2700, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37469165

RESUMO

OBJECTIVE: Higher levels of biochemical blood markers of brain injury have been described immediately after tonic-clonic seizures and in drug-resistant epilepsy, but the levels of such markers in epilepsy in general have not been well characterized. We analyzed neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and tau in a regional hospital-based epilepsy cohort and investigated what proportion of patients have levels suggesting brain injury, and whether certain epilepsy features are associated with high levels. METHODS: Biomarker levels were measured in 204 patients with an epilepsy diagnosis participating in a prospective regional biobank study, with age and sex distribution correlating closely to that of all patients seen for epilepsy in the health care region. Absolute biomarker levels were assessed between two patient groups: patients reporting seizures within the 2 months preceding inclusion and patients who did not have seizures for more than 1 year. We also assessed the proportion of patients with above-normal levels of NfL. RESULTS: NfL and GFAP, but not tau, increased with age. Twenty-seven patients had abnormally high levels of NfL. Factors associated with such levels were recent seizures (p = .010) and epileptogenic lesion on radiology (p = .001). Levels of NfL (p = .006) and GFAP (p = .032) were significantly higher in young patients (<65 years) with seizures ≤2 months before inclusion compared to those who reported no seizures for >1 year. NfL and GFAP correlated weakly with the number of days since last seizure (NfL: rs = -.228, p = .007; GFAP: rs = -.167, p = .048) in young patients. NfL also correlated weakly with seizure frequency in the last 2 months (rs = .162, p = .047). SIGNIFICANCE: Most patients with epilepsy do not have biochemical evidence of brain injury. The association with seizures merits further study; future studies should aim for longitudinal sampling and examine whether individual variations in NfL or GFAP levels could reflect seizure activity.


Assuntos
Lesões Encefálicas , Epilepsia , Humanos , Estudos Prospectivos , Proteína Glial Fibrilar Ácida , Filamentos Intermediários , Proteínas de Neurofilamentos , Biomarcadores , Convulsões
3.
Eur J Neurol ; 30(10): 3228-3235, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37483157

RESUMO

BACKGROUND AND PURPOSE: N-methyl-d-aspartate receptor (NMDAR) and leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis are important types of autoimmune encephalitis (AE) with significant morbidity. In this study, we used a proteomic approach in search of novel clinically relevant biomarkers in these types of encephalitides. METHODS: Swedish and Czech tertiary neuroimmunology centers collaborated in this retrospective exploratory study. Fifty-eight cerebrospinal fluid (CSF) samples of 28 patients with AE (14 definite NMDAR, 14 with definite LGI1 encephalitis) and 30 controls were included. CSF samples were analyzed using proximity extension assay technology (Olink Target 96 Inflammation panel). For each CSF sample, 92 proteins were measured. Clinical variables were retrospectively collected, and correlations with protein levels were statistically analyzed. RESULTS: Patients and controls differed significantly in the following 18 biomarkers: TNFRSF9, TNFRSF12, TNFRSF14, TNFß, TNFα, IL7, IL10, IL12B, IFNγ, CD5, CD6, CASP8, MMP1, CXCL8, CXCL10, CXCL11, IL20RA, and sirtuin 2 (SIRT2). In LGI1 encephalitis, no clinically useful association was found between biomarkers and clinical variables. In the NMDAR encephalitis group, SIRT2, TNFß, and CD5 were significantly associated with ovarian teratoma. For SIRT2, this was true even for the first patients' CSF sample (SIRT2 without vs. with tumor, mean ± SD = 2.2 ± 0.29 vs. 2.88 ± 0.48; p = 0.007, 95% confidence interval = -1.15 to -0.22; r statistic in point-biserial correlation (rpb) = 0.66, p = 0.011). SIRT2 was positively correlated with age (rpb = 0.39, p = 0.018) and total hospital days (r = 0.55, p = <0.001). CONCLUSIONS: SIRT2 should be investigated as a biomarker of paraneoplastic etiology in NMDAR encephalitis.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Feminino , Humanos , Recém-Nascido , Encefalite Antirreceptor de N-Metil-D-Aspartato/líquido cefalorraquidiano , Autoanticorpos , Biomarcadores/líquido cefalorraquidiano , Proteômica , Estudos Retrospectivos , Sirtuína 2
4.
Eur J Neurol ; 30(9): 2602-2610, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37312655

RESUMO

BACKGROUND AND PURPOSE: Autoantibodies have been found to contribute to pathology and are used in the diagnosis of some neurological diseases. We examined the prevalence of autoantibodies in patients with various neurological diseases and whether patients who had autoantibodies differed in age, sex, or disability from those who did not. METHODS: We examined the prevalence of neural surface and onconeural autoantibodies in cerebrospinal fluid (CSF) and serum from patients with multiple sclerosis (n = 64), Parkinson disease plus atypical parkinsonism (n = 150), amyotrophic lateral sclerosis (n = 43), or autoimmune encephalitis (positive control; n = 7) and a healthy control group (n = 37). A total of 12 onconeural autoantibodies and six neural surface autoantibodies were tested in all participants. RESULTS: Autoantibodies were present in all cohorts. The prevalence of autoantibodies was high (>80%) in the autoimmune encephalitis cohort but low (<20%) in all other cohorts. When comparing patients within cohorts who were positive for autoantibodies to patients who were not, there was no difference in age, sex, and disability. This was apart from the multiple sclerosis and Parkinson disease plus atypical parkinsonism cohorts, where those with positivity for autoantibodies in the CSF were significantly older. CONCLUSIONS: The presence of the autoantibodies examined does not appear to have a substantial clinical impact within the diseases examined in this study. The presence of autoantibodies in all cohorts presents a risk for misdiagnosis when the method is used incorrectly on patients with atypical clinical presentation.


Assuntos
Esclerose Múltipla , Doença de Parkinson , Humanos , Autoanticorpos , Doença de Parkinson/diagnóstico , Esclerose Múltipla/diagnóstico , Erros de Diagnóstico
5.
Eur J Neurol ; 30(12): 3789-3798, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37522464

RESUMO

BACKGROUND AND PURPOSE: Hybrid immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develops from a combination of natural infection and vaccine-generated immunity. Multiple sclerosis (MS) disease-modifying therapies (DMTs) have the potential to impact humoral and cellular immunity induced by SARS-CoV-2 vaccination and infection. The aims were to compare antibody and T-cell responses after SARS-CoV-2 mRNA vaccination in persons with MS (pwMS) treated with different DMTs and to assess differences between naïvely vaccinated pwMS and pwMS with hybrid immunity vaccinated following a previous SARS-CoV-2 infection. METHODS: Antibody and T-cell responses were determined in pwMS at baseline and 4 and 12 weeks after the second dose of SARS-CoV-2 vaccination in 143 pwMS with or without previous SARS-CoV-2 infection and 40 healthy controls (HCs). The MS cohort comprised natalizumab (n = 22), dimethylfumarate (n = 23), fingolimod (n = 38), cladribine (n = 30), alemtuzumab (n = 17) and teriflunomide (n = 13) treated pwMS. Immunoglobulin G antibody responses to SARS-CoV-2 antigens were measured using a multiplex bead assay and FluoroSpot was used to assess T-cell responses (interferon γ and interleukin 13). RESULTS: Humoral and T-cell responses to vaccination were comparable between naïvely vaccinated HCs and pwMS treated with natalizumab, dimethylfumarate, cladribine, alemtuzumab and teriflunomide, but were suppressed in fingolimod-treated pwMS. Both fingolimod-treated pwMS and HCs vaccinated following a previous SARS-CoV-2 infection had higher antibody levels 4 weeks after vaccination compared to naïvely vaccinated individuals. Antibody and interferon γ levels 12 weeks after vaccination were positively correlated with time from last treatment course of cladribine. CONCLUSION: These findings are of relevance for infection risk mitigation and for vaccination strategies amongst pwMS undergoing DMT.


Assuntos
COVID-19 , Esclerose Múltipla , Humanos , Esclerose Múltipla/tratamento farmacológico , Cladribina , Natalizumab , Vacinas contra COVID-19/uso terapêutico , SARS-CoV-2 , Interferon gama , Alemtuzumab , Fumarato de Dimetilo , Cloridrato de Fingolimode , COVID-19/prevenção & controle , Vacinação , Anticorpos , Imunidade Adaptativa , Anticorpos Antivirais
6.
J Peripher Nerv Syst ; 28(3): 407-414, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37288802

RESUMO

BACKGROUND AND AIMS: Guillain-Barré syndrome (GBS) is a rare, acute neuropathy characterized by ascending muscle weakness. Age, axonal GBS variants, and antecedent Campylobacter jejuni infection are associated with severe GBS, but the detailed mechanisms of nerve damage are only partly explored. Pro-inflammatory myeloid cells express NADPH oxidases (NOX) that generate tissue-toxic reactive oxygen species (ROS) that are implicated in neurodegenerative diseases. This study analyzed the impact of variants of the gene encoding the functional NOX subunit CYBA (p22phox ) on acute severity, axonal damage, and recovery in adult GBS patients. METHODS: Extracted DNA from 121 patients was genotyped for allelic variation at rs1049254 and rs4673 within CYBA using real-time quantitative polymerase chain reaction. Serum neurofilament light chain was quantified by single molecule array. Patients were followed for severity and motor function recovery for up to 13 years. RESULTS: CYBA genotypes linked to reduced formation of ROS, i.e. rs1049254/G and rs4673/A, were significantly associated with unassisted ventilation, shorter time to normalization of serum neurofilament light chain and shorter time to regained motor function. Residual disability at follow-up was confined to patients carrying CYBA alleles associated with high formation of ROS. INTERPRETATION: These findings implicate NOX-derived ROS in GBS pathophysiology and CYBA alleles as biomarkers of severity.


Assuntos
Síndrome de Guillain-Barré , Adulto , Humanos , Alelos , Biomarcadores , Síndrome de Guillain-Barré/genética , Síndrome de Guillain-Barré/fisiopatologia , NADPH Oxidases/genética , Espécies Reativas de Oxigênio , Gravidade do Paciente
7.
Proc Natl Acad Sci U S A ; 117(23): 12952-12960, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32457139

RESUMO

Effective biomarkers for multiple sclerosis diagnosis, assessment of prognosis, and treatment responses, in particular those measurable in blood, are largely lacking. We have investigated a broad set of protein biomarkers in cerebrospinal fluid (CSF) and plasma using a highly sensitive proteomic immunoassay. Cases from two independent cohorts were compared with healthy controls and patients with other neurological diseases. We identified and replicated 10 cerebrospinal fluid proteins including IL-12B, CD5, MIP-1a, and CXCL9 which had a combined diagnostic efficacy similar to immunoglobulin G (IgG) index and neurofilament light chain (area under the curve [AUC] = 0.95). Two plasma proteins, OSM and HGF, were also associated with multiple sclerosis in comparison to healthy controls. Sensitivity and specificity of combined CSF and plasma markers for multiple sclerosis were 85.7% and 73.5%, respectively. In the discovery cohort, eotaxin-1 (CCL11) was associated with disease duration particularly in patients who had secondary progressive disease (PCSF < 4 × 10-5, Pplasma < 4 × 10-5), and plasma CCL20 was associated with disease severity (P = 4 × 10-5), although both require further validation. Treatment with natalizumab and fingolimod showed different compartmental changes in protein levels of CSF and peripheral blood, respectively, including many disease-associated markers (e.g., IL12B, CD5) showing potential application for both diagnosing disease and monitoring treatment efficacy. We report a number of multiple sclerosis biomarkers in CSF and plasma for early disease detection and potential indicators for disease activity. Of particular importance is the set of markers discovered in blood, where validated biomarkers are lacking.


Assuntos
Quimiocina CCL11/análise , Quimiocina CCL20/sangue , Inflamação/imunologia , Esclerose Múltipla/diagnóstico , Adulto , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Estudos de Casos e Controles , Quimiocina CCL11/imunologia , Quimiocina CCL20/imunologia , Estudos de Coortes , Feminino , Humanos , Inflamação/sangue , Inflamação/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/imunologia , Prognóstico , Proteômica , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Adulto Jovem
8.
Perfusion ; : 2676591231213506, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37933726

RESUMO

BACKGROUND: Isolated limb perfusion (ILP) is a regional cancer treatment in which high-dose chemotherapy is administered in an isolated extremity. The main side effect is regional toxicity, which occasionally leads to nerve damage. Measuring neuroaxonal biomarkers, might be a method predicting such complications. Therefore, the primary aim of the study is to investigate if neuronal biomarkers are measurable and alters in an isolated extremity during ILP. Secondly, if postoperative regional toxicity, alterations in sensitivity, and/or muscle strength are correlated to the biomarker levels. METHODS: Eighteen scheduled ILP-patients were included in the study. Glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and tau concentrations were measured in plasma sampled preoperatively, at the start and end of the ILP, on days 3 and 30, using ultrasensitive Single molecule array (Simoa) technology. The patients were assessed by a physiotherapist pre- and postoperatively. RESULTS: At ILP end, significantly higher NfL and tau levels were measured in the extremity than in the corresponding systemic circulation (NfL; 17 vs 6 ng/L, p < .01, tau; 1.8 vs 0.6 ng/L, p < .01), and the extremity levels were significantly increased at ILP end (NfL; 66 ± 37%, p < .001, tau; 75 ± 45%, p = .001). On days 3 and 30, significantly increased NfL and GFAP levels were measured systemically (NfL day 3: 69 ± 30%, p < .001; day 30: 76 ± 26%, p < .001; GFAP day 3: 33 ± 22%, p < .002; day 30: 33 ± 23%, p ≤ .004). Finally, no significant correlations were found between regional toxicity or between postoperative muscle or sensitivity decrease and biomarker release. CONCLUSION: During ILP, NfL and tau levels increased significantly. No obvious correlations were observed between biomarker release and regional toxicity or decreased muscle strength or sensitivity, although large-scale studies are warranted.

9.
Mult Scler ; 28(6): 872-884, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34392718

RESUMO

BACKGROUND: Neurofilament light (NFL) has been increasingly recognized for prognostic and therapeutic decisions. OBJECTIVE: To validate the utility of cerebrospinal fluid NFL (cNFL) as a biomarker in clinical practice of relapsing-remitting multiple sclerosis (RRMS). METHODS: RRMS patients (n = 757) who had cNFL analyzed as part of the diagnostic work-up in a single academic multiple sclerosis (MS) center, 2001-2018, were retrospectively identified. cNFL concentrations were determined with two different immunoassays and the ratio of means between them was used for normalization. RESULTS: RRMS with relapse had 4.4 times higher median cNFL concentration (1134 [interquartile range (IQR) 499-2744] ng/L) than those without relapse (264 [125-537] ng/L, p < 0.001) and patients with gadolinium-enhancing lesions had 3.3 times higher median NFL (1414 [606.8-3210] ng/L) than those without (426 [IQR 221-851] ng/L, p < 0.001). The sensitivity and specificity of cNFL to detect disease activity was 75% and 98.5%, respectively. High cNFL at MS onset predicted progression to Expanded Disability Status Scale (EDSS) ⩾ 3 (p < 0.001, hazard ratios (HR) = 1.89, 95% CI = 1.44-2.65) and conversion to secondary progressive MS (SPMS, p = 0.001, HR = 2.5, 95% CI = 1.4-4.2). CONCLUSIONS: cNFL is a robust and reliable biomarker of disease activity, treatment response, and prediction of disability and conversion from RRMS to SPMS. Our data suggest that cNFL should be included in the assessment of patients at MS-onset.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Biomarcadores/líquido cefalorraquidiano , Progressão da Doença , Humanos , Filamentos Intermediários/patologia , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico , Esclerose Múltipla Recidivante-Remitente/patologia , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Recidiva , Sistema de Registros , Estudos Retrospectivos
10.
Mult Scler ; 28(13): 2070-2080, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35856574

RESUMO

BACKGROUND: Accumulating evidence supports the efficacy of administering natalizumab (NZ) with extended-interval dosing (EID) in patients with relapsing-remitting multiple sclerosis (RRMS). OBJECTIVES: We switched NZ dosing from 4-week to 6-week intervals in patients with RRMS, and investigated the effect on serum neurofilament light chain (sNfL) concentrations. METHODS: We included two cohorts of patients with RRMS treated with NZ: one received the standard-interval dosing (4 weeks) at baseline, and were switched to 6-week intervals (EID4-6, N = 45). The other cohort received EID (5- or 6-week intervals) both at baseline and during follow-up (EID5/6, N = 25). Serum samples were collected in the EID4-6 cohort at every NZ infusion, for 12 months. The primary outcome was the change in sNfL concentrations after switching to EID. RESULTS: The baseline mean sNfL concentration in the EID4-6 cohort was 10.5 ng/L (standard deviation (SD) = 6.1), and it remained unchanged at 12 months. Moreover, individual sNfL concentrations did not change significantly after extending the NZ dosing intervals. In addition, the EID4-6 and EID5/6 cohorts had similar baseline sNfL concentrations. CONCLUSION: We concluded that extending the NZ dosing interval did not increase axonal damage, as determined with sNfL, in patients with RRMS.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Estudos de Coortes , Humanos , Filamentos Intermediários , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab , Proteínas de Neurofilamentos
11.
J Neurochem ; 159(3): 618-628, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34478561

RESUMO

Kappa free light chain (KFLC) index, a measure for intrathecal production of free kappa chains, has been increasingly recognized for its diagnostic potential in multiple sclerosis (MS) as a quantitative alternative to IgG oligoclonal bands (OCBs). Our objective was to investigate the sensitivity, specificity, and overall diagnostic accuracy of KFLC index in MS. KFLC index was prospectively determined as part of the diagnostic workup in patients with suspected MS (n = 327) between May 2013 and February 2020. Patients with clinically isolated syndrome (CIS), radiologically isolated syndrome (RIS), and MS had markedly higher KFLC index (44.6, IQR 16-128) compared with subjects with other neuro-inflammatory disorders (ONID) and symptomatic controls (SC) (2.19, IQR 1.68-2.98, p < 0.001). KFLC index had a sensitivity of 0.93 (95% CI 0.88-0.95) and specificity of 0.87 (95% CI 0.8-0.92) to discriminate CIS/RIS/MS from ONID and SC (AUC 0.94, 95% CI 0.91-0.97, p < 0.001). KFLC index and intrathecal fraction (IF) KFLC had similar accuracies to detect MS. Treatment with disease-modifying therapy (DMT) did not influence the level of KFLC index and it was not affected by demographic factors or associated with degenerative or inflammatory biomarkers in cerebrospinal fluid (CSF). KFLC index in MS diagnostics has methodological advantages compared to OCB and is independent to subjective interpretation. Moreover, it is an attractive diagnostic tool since the diagnostic specificity and sensitivity of KFLC index are similar with that of OCBs and KFLCIF and better than for IgG index. We show that KFLC index was influenced neither by DMT nor by demographic factors or other inflammatory or degenerative processes in MS as determined by biomarkers in CSF.


Assuntos
Cadeias Leves de Imunoglobulina/análise , Esclerose Múltipla/diagnóstico , Adulto , Biomarcadores , Doenças Desmielinizantes/diagnóstico , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Imunoglobulina G/análise , Inflamação/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla/diagnóstico por imagem , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Medula Espinal/química , Medula Espinal/metabolismo
12.
J Neurol Neurosurg Psychiatry ; 92(2): 189-194, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33106366

RESUMO

OBJECTIVE: To compare outcomes after treatment with autologous haematopoietic stem cell transplantation (AHSCT) and alemtuzumab (ALZ) in patients with relapsing-remitting multiple sclerosis. METHODS: Patients treated with AHSCT (n=69) received a conditioning regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulinerG (6.0 mg/kg). Patients treated with ALZ (n=75) received a dose of 60 mg over 5 days, a repeated dose of 36 mg over 3 days after 1 year and then as needed. Follow-up visits with assessment of the expanded disability status scale score, adverse events and MR investigations were made at least yearly. RESULTS: The Kaplan-Meier estimates of the primary outcome measure 'no evidence of disease activity' was 88% for AHSCT and 37% for ALZ at 3 years, p<0.0001. The secondary endpoint of annualised relapse rate was 0.04 for AHSCT and 0.1 for ALZ, p=0.03. At last follow-up, the proportions of patients who improved, were stable or worsened were 57%/41%/1% (AHSCT) and 45%/43%/12% (ALZ), p=0.06 Adverse events grade three or higher were present in 48/69 patients treated with AHSCT and 0/75 treated with ALZ in the first 100 days after treatment initiation. The most common long-term adverse event was thyroid disease with Kaplan-Meier estimates at 3 years of 21% for AHSCT and 46% for ALZ, p=0.005. CONCLUSIONS: In this observational cohort study, treatment with AHSCT was associated with a higher likelihood of maintaining 'no evidence of disease activity'. Adverse events were more frequent with AHSCT in the first 100 days, but thereafter more common in patients treated with ALZ.


Assuntos
Alemtuzumab/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Esclerose Múltipla Recidivante-Remitente/terapia , Fármacos Neuroprotetores/uso terapêutico , Adulto , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Resultado do Tratamento
13.
Acta Neurol Scand ; 144(5): 566-575, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34278566

RESUMO

OBJECTIVES: In multiple sclerosis (MS), fatigue is the most prevalent cause of impaired ability to work. In narcolepsy, daytime sleepiness is the main symptom but some studies indicate fatigue being present. We aimed to assess fatigue and associated features in patients with MS or narcolepsy and healthy controls and to assess whether clinical parameters separate fatigued (MS-F) and non-fatigued MS patients (MS-NoF). MATERIALS & METHODS: In this non-interventional cross-sectional study, we recruited 34 MS patients, 15 narcolepsy type 1 patients and 17 healthy controls. An interviewer administered the Fatigue Severity Scale (FSS), the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale, the Patient Health Questionnaire-9 and the Saltin-Grimby Physical Activity Level Scale. Information about clinical parameters and current treatments was collected. RESULTS: In its fatigue profile, MS-F resembled the narcolepsy group rather than MS-NoF, which resembled the healthy control group. ISI alone was significantly associated with FSS, and only in MS-NoF and healthy controls; in MS-F and the narcolepsy group, no variable was associated with FSS. Months since diagnosis was the only clinical variable significantly separating MS-F from MS-NoF. In MS, disease duration correlated with fatigue. No clinical variables correlated with fatigue in the narcolepsy group. CONCLUSIONS: Fatigued MS patients resemble narcolepsy patients more than they resemble non-fatigued MS patients, who resemble healthy controls. Insomnia is the main factor associated with fatigue in MS, while disease duration is the only clinical variable separating fatigued and non-fatigued MS patients. In fatigued patients, variance in fatigue cannot be explained by insomnia, daytime sleepiness, depression or level of exercise.


Assuntos
Distúrbios do Sono por Sonolência Excessiva , Esclerose Múltipla , Narcolepsia , Distúrbios do Início e da Manutenção do Sono , Estudos Transversais , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Distúrbios do Sono por Sonolência Excessiva/etiologia , Fadiga/diagnóstico , Fadiga/epidemiologia , Fadiga/etiologia , Humanos , Esclerose Múltipla/complicações , Narcolepsia/complicações , Narcolepsia/diagnóstico , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/etiologia
14.
Acta Neurol Scand ; 142(2): 161-168, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32415852

RESUMO

OBJECTIVES: The risk of developing multiple sclerosis (MS) increases (OR: 3.1) after infectious mononucleosis (IM). However, the nature of this link is obscure. We tested the hypothesis that IM might incur long-term sequelae, including low-key inflammatory activity, with characteristics of an MS endophenotype (or presymptomatic trait) and that assays of MS-relevant cyto-/chemokines in the cerebrospinal fluid (CSF) post-IM may show a trend in this direction. MATERIALS AND METHODS: We selected seven CSF cytokines (IL-1b, IL-6, YKL-40, TNF-alpha) or chemokines (IL-8, CCL2, IP-10), representing pro-inflammatory factors previously associated with MS. We assayed the CSF levels of these seven cyto-/chemokines in healthy individuals with a median follow-up time of 10 years after serologically confirmed IM (post-IM group, n = 22), and in healthy controls without a history of IM (n = 19). A group of MS patients (n = 23) were included as reference. RESULTS: The CSF levels of IP-10, YKL-40, and CCL-2 were higher in the post-IM group than in our IM unexposed controls (P = .021, .049, .028). Seven of seven cyto-/chemokine assays showed a trend in the predicted direction (P of binomial ratio = .008). However, this trend was non-significant in a multivariate test (P = .22). A power analysis indicated that similar studies including a larger cohort would be numerically realistic. CONCLUSIONS: These results do not reject the hypothesis that the established epidemiological association between IM and MS results from a stepwise inflammatory propagation from IM sequelae to an MS endophenotype (or presymptomatic trait) in a proportion of IM patients, pending confirmation with adequate power.


Assuntos
Mononucleose Infecciosa/líquido cefalorraquidiano , Mononucleose Infecciosa/epidemiologia , Mediadores da Inflamação/líquido cefalorraquidiano , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/epidemiologia , Adolescente , Adulto , Biomarcadores/líquido cefalorraquidiano , Estudos de Coortes , Citocinas/líquido cefalorraquidiano , Feminino , Humanos , Mononucleose Infecciosa/diagnóstico , Interleucina-1beta/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , Adulto Jovem
15.
J Neuroinflammation ; 16(1): 16, 2019 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-30678707

RESUMO

BACKGROUND: HIV-1 infects the central nervous system (CNS) shortly after transmission. This leads to a chronic intrathecal immune activation. YKL-40, a biomarker that mainly reflects activation of astroglial cells, has not been thoroughly investigated in relation to HIV. The objective of our study was to characterize cerebrospinal fluid (CSF) YKL-40 in chronic HIV infection, with and without antiretroviral treatment (ART). METHODS: YKL-40, neopterin, and the axonal marker neurofilament light protein (NFL) were analyzed with ELISA in archived CSF samples from 120 HIV-infected individuals (85 untreated neuroasymptomatic patients, 7 with HIV-associated dementia, and 28 on effective ART) and 39 HIV-negative controls. RESULTS: CSF YKL-40 was significantly higher in patients with HIV-associated dementia compared to all other groups. It was also higher in untreated neuroasymptomatic individuals with CD4 cell count < 350 compared to controls. Significant correlations were found between CSF YKL-40 and age (r = 0.38, p < 0.001), CD4 (r = - 0.36, p < 0.001), plasma HIV RNA (r = 0.35, p < 0.001), CSF HIV RNA (r = 0.35, p < 0.001), CSF neopterin (r = 0.40, p < 0.001), albumin ratio (r = 0.44, p < 0.001), and CSF NFL (r = 0.71, p < 0.001). Age, CD4 cell count, albumin ratio, and CSF HIV RNA were found as independent predictors of CSF YKL-40 concentrations in multivariable analysis. In addition, CSF YKL-40 was revealed as a strong independent predictor of CSF NFL together with age, CSF neopterin, and CD4 cell count. CONCLUSIONS: CSF YKL-40 is a promising biomarker candidate for understanding the pathogenesis of HIV in the CNS. The strong correlation between CSF YKL-40 and NFL suggests a pathogenic association between astroglial activation and axonal injury, and implies its utility in assessing the prognostic value of YKL-40.


Assuntos
Lesões Encefálicas/líquido cefalorraquidiano , Lesões Encefálicas/etiologia , Proteína 1 Semelhante à Quitinase-3/líquido cefalorraquidiano , Infecções por HIV/complicações , Adulto , Correlação de Dados , Estudos Transversais , Citocinas/líquido cefalorraquidiano , Feminino , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neopterina/líquido cefalorraquidiano , Proteínas de Neurofilamentos/líquido cefalorraquidiano
16.
BMC Neurol ; 19(1): 89, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053103

RESUMO

BACKGROUND: Missense mutations in SAMD9L gene is associated with ataxia-pancytopenia syndrome (ATXPC), OMIM#159550. Common clinical features in these patients include neurological and hematological symptoms. The phenotype and age of onset is variable. CASE PRESENTATION: In this case report whole exome sequencing (WES) revealed a not previously reported de novo variant c.2686 T > G, p.(Phe896Val) in SAMD9L in a patient with widespread findings of slow developing pathology in the peripheral and central nervous system. The clinical picture was dominated by neurological symptoms, unlike previously described cases, and in addition dural ectasias and multiple cysts in the brain was observed using magnetic resonance imaging. CONCLUSIONS: This case underscores the effect of variable expressivity, i.e. different mutations in the same gene can cause different phenotypes.


Assuntos
Doenças Desmielinizantes/genética , Leucoencefalopatias/genética , Doenças do Sistema Nervoso Periférico/genética , Proteínas Supressoras de Tumor/genética , Adolescente , Criança , Pré-Escolar , Cistos/genética , Feminino , Humanos , Lactente , Recém-Nascido , Mutação , Mutação de Sentido Incorreto , Fenótipo
17.
Acta Neurol Scand ; 140(2): 147-156, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31070772

RESUMO

BACKGROUND: Mortality is increased in parkinsonian disorders, moderately in Parkinson's disease (PD) but markedly in atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). Still, there are no reliable quantitative biomarkers for mortality. The cerebrospinal fluid (CSF) neurodegeneration biomarkers such as neurofilament light chain (NF-L), total tau (t-tau), and the tau pathology marker phosphorylated tau (p-tau) are related to mortality in other neurological disorders (eg, amyotrophic lateral sclerosis, Alzheimer's disease), but have not been investigated in this respect in parkinsonian disorders. AIMS: To investigate the CSF biomarkers' (NF-L, t-tau, and p-tau) relationship to mortality in parkinsonian disorders. METHODS: Demographic, mortality, and CSF data were collected from 68 PD and 83 APD patients. Survival analysis was conducted using Cox regression, with age at lumbar puncture, gender, diagnosis, and levels of CSF biomarkers as predictors. RESULTS: NF-L in CSF was associated with increased mortality in synucleinopathies (PD, MSA; HR 3.698 [2.196-6.228, 95% confidence interval (CI)], P < 0.001), in PSP (HR 2.767 [1.126-6.802 95% CI], P = 0.027), and in the entire cohort (HR 1.661 [1.082-2.55, 95% CI], P = 0.02). t-Tau in CSF was associated with increased mortality in PSP (HR 9.587 [1.143-80.418], P = 0.037). p-Tau in CSF was associated with decreased mortality in synucleinopathies (HR 0.196 [0.041-0.929, 95% CI], P = 0.040). Atypical parkinsonian disorders and tauopathies were associated with higher mortality (HR 8.798 [4.516-17.14, 95% CI] and HR 3.040 [1.904-4.854], respectively, P < 0.001). CONCLUSION: NF-L and tau protein in CSF might be useful for mortality prognosis in patients with parkinsonian disorders and should be investigated in larger studies.


Assuntos
Proteínas de Neurofilamentos/líquido cefalorraquidiano , Transtornos Parkinsonianos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Parkinsonianos/mortalidade , Transtornos Parkinsonianos/patologia
18.
Acta Neurol Scand ; 139(5): 422-427, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30657162

RESUMO

BACKGROUND: Little is known about what leads to recovery between relapses in multiple sclerosis (MS), particularly following treatment. In the past, it has been demonstrated that soluble neural cell adhesion molecule (sNCAM), a putative biomarker of neuroplasticity, increased following steroid treatment in the Cerebrospinal fluid (CSF) of MS subjects undergoing acute relapses. Taking this a step further, we have evaluated the effect of disease-modifying treatment (DMTs) on CSF sNCAM levels in various subtypes of MS. METHODS: We measured CSF sNCAM levels at baseline and after 12-24 months of DMT in 69 patients, 49 relapsing-remitting MS (RRMS), 20 progressive MS(PMS), and 24 healthy controls (HC) using an in-house ELISA. Of this, 31 patients had received natalizumab, 17 mitoxantrone, and 21 fingolimod. Changes in disability were measured using EDSS and disease severity by MSSS. In conjunction, CSF NfL levels were also measured. RESULTS: At baseline, the mean sNCAM level was 268.7 ng/mL (SD: 109 ng/mL) in MS patients compared with 340.6 ng/ml (SD: 139 ng/mL) in HC, and PMS had significantly lower sNCAM (239.2 ng/mL, SD: 123.0, P = 0.019) compared to RRMS (269.4, SD: 127.4, P = 0.043). After natalizumab and mitoxantrone treatments, we observed an increase in mean sNCAM. However, in the fingolimod-treated group, mean sNCAM decreased. There was no correlation found with EDSS or MSSS, or NfL levels as a whole. CONCLUSIONS: Cerebrospinal fluid sNCAM levels were found to be lower in MS than in HC and the lowest sNCAM levels were found in PMS. Following natalizumab and mitoxantrone treatments, we observed an elevation in sNCAM levels, an effect that was not observed following fingolimod treatment. These changes, however, did not appear to correlate with disability in the short-term or NfL levels.


Assuntos
Biomarcadores/líquido cefalorraquidiano , Antígeno CD56/líquido cefalorraquidiano , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Esclerose Múltipla Recidivante-Remitente/dietoterapia , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Cloridrato de Fingolimode/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Mitoxantrona/uso terapêutico , Esclerose Múltipla/líquido cefalorraquidiano , Natalizumab/uso terapêutico
19.
Acta Neurol Scand ; 140(3): 177-183, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31087810

RESUMO

BACKGROUND: Elevated levels of the cerebrospinal fluid (CSF) neuronal injury markers (neurofilament light chain [NF-L] and total tau protein [t-tau]) and of the astroglial marker glial fibrillary acidic protein (GFAP) are found in etiologically different neurological disorders affecting the peripheral and the central nervous system. AIMS: To explore the role of CSF biomarkers in the clinical management of patients admitted for alarming neurological symptoms, but in whom neurological disorders could be excluded. METHODS: Study participants were patients seeking medical attention for neurological symptoms primarily considered to be caused by a neurological diagnosis and investigated according to clinical routine. Demographic, clinical, and CSF data were extracted retrospectively from medical records. Patients with a final neurological diagnosis were excluded. RESULTS: Out of 990 patients, 900 with a neurological diagnosis were excluded leaving 90 patients without a final neurological diagnosis. Sixty-eight (75.6%) were females. Median (range) age at lumbar puncture was 34.7 (16.9-65.1) years. Age-adjusted CSF-NF-L, CSF-t-tau, and CSF-GFAP concentrations were normal in 89 (98.9%), 86 (95.6%), and 87 (96.7%) patients, respectively. CONCLUSION: In patients with significant neurological symptoms but in whom a neurological diagnosis could not be made, the CSF markers NF-L, t-tau, and GFAP did not indicate signs of neuronal or astroglial cell damage close to symptom onset. Consequently, increased levels of CSF markers are not expected in this patient group and, if present, should raise suspicion of underlying neurological disorders and motivate further investigations.


Assuntos
Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/patologia
20.
J Neurochem ; 146(3): 322-332, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29676479

RESUMO

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Several biomarkers including proteins and lipids have been reported in MS cerebrospinal fluid (CSF), reflecting different aspects of the pathophysiology particularly of relapsing-remitting MS (RRMS). Sulfatide, abundant in the myelin sheath and a proposed target for autoimmune attack in MS, has been reported altered in MS CSF. Here, we investigated the potential of CSF sulfatide and its isoforms as biomarkers in MS. A highly sensitive and quantitative mass spectrometry method was employed to determine levels of sulfatide isoforms in CSF from RRMS and progressive MS (PMS) patients, and healthy donors (HD). We demonstrate that levels of total CSF sulfatide and C24:1, C26:1, and C26:1-OH isoforms were significantly increased in PMS compared with RRMS patients and HD, while C23:0-OH was significantly decreased in CSF from PMS patients compared to the other two groups. Multivariate discriminant analysis showed that CSF sulfatide isoform pattern in PMS patients was distinct and non-overlapping with that of RRMS patients and HD. Sulfatide levels did not correlate with tested biomarkers or clinical parameters. The results suggest that CSF sulfatide isoform levels may be used to discriminate the phenotype of MS and might play a role in the progression of the disease.


Assuntos
Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico , Sulfoglicoesfingolipídeos/líquido cefalorraquidiano , Adulto , Estudos de Casos e Controles , Citocinas/líquido cefalorraquidiano , Progressão da Doença , Feminino , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Análise de Componente Principal , Isoformas de Proteínas/líquido cefalorraquidiano , Curva ROC , Sulfoglicoesfingolipídeos/química , Linfócitos T/metabolismo , Adulto Jovem
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