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BACKGROUND: Incidence and prevalence rates of myasthenia gravis (MG) vary considerably across studies, and mortality risk is rarely addressed. We examined the prevalence and incidence rates, mortality and factors associated with mortality with MG. METHOD: This was a registry linkage study based on nationwide health and administrative registries of Denmark, Finland and Sweden (populations of 5.9, 5.6 and 10.5 million, respectively). Patients with MG were identified based on International Classification of Diseases codes from inpatient and outpatient specialised care registries. Yearly prevalence, incidence and mortality rates in relation to the total background population were calculated from 2000 to 2020 (study period). The causes of death and factors associated with mortality were addressed separately. RESULTS: The overall incidence of MG was 1.34 (95% CI 1.27 to 1.41), 1.68 (95% CI 1.60 to 1.75) and 1.62 (95% CI 1.56 to 1.68) per 100 000, and the overall prevalence per 100 000 was 18.56 (95% CI 18.31 to 18.81), 20.89 (95% CI 20.62 to 21.16) and 23.42 (95% CI 23.21 to 23.64) in Denmark, Finland and Sweden, respectively. The overall standardised mortality ratio (SMR) was 1.32 (95% CI 1.23 to 1.42) among patients with MG in Denmark, 1.23 (95% CI 1.15 to 1.33) in Finland, and 1.20 (95% CI 1.14 to 1.26) in Sweden, with higher SMR observed in women than men. Annual incidence and prevalence increased over time, whereas the SMR remained stable. The most common causes of death were MG, chronic ischaemic heart disease and acute myocardial infarction. CONCLUSIONS: This population-based study from three Nordic countries highlights the need for improved care of patients with MG, especially young women.
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BACKGROUND AND PURPOSE: There is an absence of data from large population-based cohort studies on the incidence of radiologically isolated syndrome (RIS). The incidence of RIS and the subsequent risk for multiple sclerosis (MS) were investigated. METHODS: A population-based, retrospective cohort study was conducted using a data-lake-based analysis of digitalized radiology reports. All brain and spinal cord magnetic resonance imaging (MRI) in people aged 16-70 during the years 2005-2010 (n = 102,224) were screened using optimized search terms to detect cases with RIS. The subjects with RIS were followed up until January 2022. RESULTS: The cumulative incidence of RIS was 0.03% when all MRI modalities were included and 0.06% when only brain MRI was included according to MAGNIMS 2018 recommendation criteria. With the Okuda 2009 criteria, the respective figures were 0.03% and 0.05% (86% concordance). The overall risk for MS after RIS was similar, 32% by using the MAGNIMS and 32% by using the Okuda definition of RIS. Individuals aged <35.5 years exhibited the most significant predisposition to MS (80%), whilst those >35.5 years had less than 10% risk of MS. MS diagnosed after RIS constituted 0.8% of the incident MS cases in the population during 2005-2010. CONCLUSIONS: A population-wide context was provided for the incidence of RIS and its relationship to MS. MAGNIMS recommendations were only slightly more sensitive to detect RIS compared to the Okuda criteria. RIS has a subtle effect on the overall incidence of MS, yet the risk for MS in individuals under the age of 35.5 years is substantial.
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Enfermedades Desmielinizantes , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/epidemiología , Estudios de Cohortes , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Enfermedades Desmielinizantes/diagnóstico por imagen , Enfermedades Desmielinizantes/epidemiología , Enfermedades Desmielinizantes/patologíaRESUMEN
The ability of thymic histopathology to predict the long-term impact of thymectomy in non-thymomatous myasthenia gravis (NTMG) is mainly uncharted. We applied digital pathology to quantitatively characterize differences of thymic histology between early-onset (EOMG) and late-onset MG (LOMG) and to investigate the role of thymic changes for thymectomy outcomes in MG. We analyzed 83 thymic H&E slides from thymectomized NTMG patients, of which 69 had EOMG and 14 LOMG, using digital pathology open-access software QuPath. We compared the results to the retrospectively assessed clinical outcome at two years after thymectomy and at the last follow-up visit where complete stable remission and minimal use of medication were primary outcomes. The automated annotation pipeline was an effective and reliable way to analyze thymic H&E samples compared to manual annotation with mean intraclass correlation of 0.80. The ratio of thymic tissue to stroma and fat was increased in EOMG compared to LOMG (p = 8.7e-07), whereas no difference was observed in the ratio of medulla to cortex between these subtypes. AChRAb seropositivity correlated with the number of ectopic germinal centers (eGC; p = 0.00067) but not with other histological areas. Patients with an increased number of eGCs had better post-thymectomy outcomes at two years after thymectomy (p = 0.0035) and at the last follow-up (p = 0.0267). ROC analysis showed that eGC area predicts thymectomy outcome in EOMG with an AUC of 0.79. Digital pathology can thus help in providing a predictive tool to the clinician, the eGC number, to guide the post-thymectomy treatment decisions in EOMG patients.
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Miastenia Gravis , Timectomía , Centro Germinal/patología , Humanos , Miastenia Gravis/tratamiento farmacológico , Miastenia Gravis/patología , Miastenia Gravis/cirugía , Pronóstico , Estudios Retrospectivos , Timectomía/métodos , Resultado del TratamientoRESUMEN
OBJECTIVES: The association of trigeminal neuralgia (TN) with multiple sclerosis (MS) is still widely unaddressed in larger, systematical clinical series. In this study, a cohort of Finnish MS patients was assessed regarding the incidence and prevalence of TN, as well as the presence of demyelinating lesions near the trigeminal ganglion, thus searching for a causative role of MS plaques in TN onset. MATERIALS & METHODS: All consecutive patients treated and followed up for MS (ICD-code G35) in Helsinki University Hospital during 2004-2017 were identified from the Finnish MS register. A hospital administrative database search was used to identify all patients treated and followed up for TN during the same period. Among the MS patients, head MRI scans available from the diagnostic phase of TN or thereafter were analysed. RESULTS: We identified a total of 2575 patients with MS and 2008 patients with TN. Both diagnoses could be verified for 55 patients, giving a prevalence of 2.1% for TN in MS. The incidence of TN in MS patients was 149/100 000 person-years (95% CI 108-190). In the general outpatient population of our neurological department, the incidence of TN was 9.9/100 000 person-years (95% CI 9.5-10.3). A demyelinating lesion in the proximity of the trigeminal ganglia was seen for 63% of the 41 patients with relevant MRI data available. CONCLUSIONS: Incidence of TN among MS patients was 15-fold higher than in the general neurological outpatient population, thus in favour of a strong association between MS and TN.
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Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/epidemiología , Neuralgia del Trigémino/diagnóstico por imagen , Neuralgia del Trigémino/epidemiología , Adulto , Anciano , Enfermedades Desmielinizantes/diagnóstico por imagen , Enfermedades Desmielinizantes/epidemiología , Femenino , Finlandia/epidemiología , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética/tendencias , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: To explore adherence, persistence, and treatment patterns in patients with multiple sclerosis (MS) in Finland treated with disease-modifying therapies (DMTs) for active MS in 2005-2018. MATERIALS AND METHODS: The study cohort was identified using the Drug Prescription Register of Social Insurance Institute, Finland. All patients had at least one prescription of glatiramer acetate (GA), beta-interferons, teriflunomide, or delayed-release dimethyl fumarate (DMF). Adherence was calculated using proportion of days covered (PDC) (cutoff ≥0.8). Time to non-persistence was calculated by the number of days on index DMT treatment before the first treatment gap (≥90 days) or switch and analyzed with time-to-event methodology. RESULTS: The cohort included 7474 MS patients (72.2% female; mean age 38.9 years). Treatment switches were steady over 2005-2012, peaked in 2015. PDC means (standard deviations) were GA, 0.87 (0.17); beta-interferons, 0.88 (0.15); DMF, 0.89 (0.14); teriflunomide, 0.93 (0.10). Adherence frequencies were GA, 78.4%; beta-interferons, 81.3%; DMF, 86.9%; teriflunomide, 91.7%. Logistic regression showed that age group, DMT and the starting year, sex, and hospital district independently affected adherence. Patients receiving teriflunomide and DMF, males, and older patients were more likely to persist on treatment. There was no difference in persistence between patients prescribed teriflunomide and DMF, or between GA and beta-interferons. CONCLUSIONS: Oral DMTs had greater adherence and persistence than injectable DMTs.
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Inmunosupresores/uso terapéutico , Cumplimiento de la Medicación/estadística & datos numéricos , Esclerosis Múltiple/tratamiento farmacológico , Adulto , Estudios de Cohortes , Femenino , Finlandia , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVES: Finland is a high-risk multiple sclerosis (MS) region, but a national MS register has not existed until 2014. In this paper, we present the Finnish MS register variables and data collected by 31 December 2018. MATERIALS AND METHODS: Numbers and data counts of MS patients in the register (ICD-10 code G35) are presented. The disease types and proportion of patients receiving disease-modifying treatments (DMTs) were analysed in five hospital districts with most complete data sets. MS prevalence in Finland was estimated using administrative hospital discharge data as an additional resource. RESULTS: There were a total of 8722 MS patients in the Finnish MS register by 31 December 2018 (71.5% females). Mean age at MS diagnosis was 38.7 years and peak prevalence was at age 50-54 years. Disease course was relapsing remitting (RRMS) in 66.7%, secondary progressive (SPMS) in 13.5%, and primary progressive (PPMS) in 7.9% of the 5365 MS patients in the selected districts with most complete data. A total of 66.0% of RRMS patients, 19.6% of SPMS patients and 9.9% of PPMS patients were receiving DMTs. By combining MS register data with databases of those hospitals that had not joined the register, the nationwide prevalence estimate was between 10 and 11 thousand patients (corresponding to crude prevalence 180-200/100 000). CONCLUSIONS: The Finnish MS register is currently used in 15/21 Finnish hospital districts. By register integration into the electronic patient files, the coverage of the register has increased to approximately 80% of the estimated Finnish MS population.
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Esclerosis Múltiple/epidemiología , Adulto , Femenino , Finlandia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Sistema de RegistrosRESUMEN
BACKGROUND: Doppler ultrasound (US) has been widely used to evaluate the cervical venous system of multiple sclerosis patients according to the hypothesis of chronic cerebrospinal venous insufficiency with contradictory results. Venous anatomy and pathology can be examined with less operator-dependent magnetic resonance imaging (MRI). Our aim is to assess the interobserver agreement in measuring internal jugular vein (IJV) cross-sectional area (CSA) in MR images and to explore the agreement between US and MRI in the detection of calibers of ≤0.3 cm2 in the IJV CSA in the prospective study. METHODS: Thirty-seven multiple sclerosis patients underwent MRI of the cervical venous system. Two independent neuroradiologists measured the CSA of IJV at the mid-thyroid level. Furthermore, the time from contrast enhancement of common carotid arteries to that of each IJV (transit time in seconds) was assessed, and recorded whether IJV or the vertebral plexus visualized first during the contrast passage. US examination had been performed earlier. RESULTS: Interobserver agreement for assessing IJV CSA in MR images was substantial: the measurements differed >0.5 cm2 between the examiners in only 5 IJVs (7%), Cohen's kappa 0.79. Transit times from common carotid artery to IJV varied between 5.1 and 14.1 sec. Fifteen patients had left-to-right asymmetry in the speed of IJV contrast filling. IJV CSA ≤ 0.3 cm2 was found in 51 IJVs on the basis of US. Ten of these IJVs (19.6%) showed IJV CSA ≤ 0.3 cm2 also in MRI. All IJVs defined as CSA ≤ 0.3 cm2 in MRI met this caliber criterion also in US. CONCLUSIONS: Interobserver agreement at the thyroid level of the IJV was good at MRI measurements. The US defines more IJVs as narrow (CSA ≤ 0.3 cm2) than MRI. The US measurements for IJV CSA are not comparable with these methods. The US seems too sensitive in terms of finding venous stenosis.
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Venas Yugulares/diagnóstico por imagen , Angiografía por Resonancia Magnética , Esclerosis Múltiple/diagnóstico por imagen , Ultrasonografía Doppler , Adulto , Velocidad del Flujo Sanguíneo , Estudios de Casos y Controles , Constricción Patológica , Femenino , Humanos , Venas Yugulares/fisiopatología , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/fisiopatología , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Estudios Prospectivos , Flujo Sanguíneo Regional , Reproducibilidad de los Resultados , Glándula Tiroides , Adulto JovenRESUMEN
Myasthenia gravis (MG) is the most common neuromuscular transmission disorder, causing weakness of skeletal muscles on exertion. The course of the disease is highly variable, symptoms and signs may change rapidly due to infection or pregnancy. MG is classified using serological, electrophysiological and pharmaceutical tools. A precise diagnosis allows for the choice of right treatment, predicts the course of disease and hence helps with the follow-up. In this review we present Finnish guidelines for diagnostics, treatment and follow-up of MG patients.
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Miastenia Gravis/diagnóstico , Miastenia Gravis/terapia , Finlandia , Humanos , Guías de Práctica Clínica como AsuntoRESUMEN
The treatment of Parkinson's disease may be initiated with dopamine agonist or MAO-B-inhibitor for people under 60-65 years of age. For older patients, the treatment may also be started with levodopa. If there are motor complications, such as on-off-symptoms, apomorphin injections can be beneficial in addition to other medications. In the case of difficult on-off-symptoms and dyskinesias in spite of optimal treatment, deep brain stimulation, duodenal levodopa infusion and apomorphine infusion should be considered. Rehabilitation can improve gait speed and balance, decrease falls and improve speech. However, with advancing disease the results are not maintained if trainino is discontinued.
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Enfermedad de Parkinson/terapia , Guías de Práctica Clínica como Asunto , Anciano , Antiparkinsonianos/uso terapéutico , Apomorfina/uso terapéutico , Estimulación Encefálica Profunda , Agonistas de Dopamina/uso terapéutico , Humanos , Levodopa/uso terapéutico , Persona de Mediana Edad , Inhibidores de la Monoaminooxidasa/uso terapéuticoRESUMEN
Treatment for relapsing-remitting multiple sclerosis (RRMS) is initiated upon fulfillment of new McDonald 2010 criteria for RRMS. In addition, lumbar puncture is an essential diagnostic method. Interferon-ß, dimethyl fumarate, glatiramer acetate and teriflunomide are the first-line immunomodulating drugs (IMD) for RRMS. If the disease is active according to clinical or MRI evaluation during the first-line IMD treatment, alemtuzumab, fingolimod or natalizumab may be considered as second-line therapies. IMD treatment is discontinued upon the transition of RRMS to secondary progressive phase. Rehabilitation should be considered at every phase of the disease.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Factores Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Humanos , Punción EspinalRESUMEN
OBJECTIVES: To identify factors associated with favorable outcome in ischemic stroke patients having considerable post-thrombolytic neurological deficits but without endovascular treatment. MATERIALS AND METHODS: We registered 1427 consecutive thrombolysis-treated ischemic stroke patients, of which 473 (33%) had ≥8 NIH Stroke Scale (NIHSS) points after thrombolysis but did not undergo any further rescue intervention. We dichotomized them based on 3-month modified Rankin Scale (mRS) to those with favorable (mRS 0-2, n = 126, 27%) and unfavorable (mRS 3-6, n = 347) outcome. Univariate and multivariable methods tested associations of baseline and post-thrombolysis parameters with outcome. RESULTS: Lower post-thrombolysis NIHSS score and younger age had strongest association with favorable outcome. Most of patients with post-thrombolytic NIHSS score ≥11 achieved unfavorable outcome. In contrast, half of patients with favorable outcome had post-thrombolytic NIHSS≤10, and 62% of patients younger than 75 years and having post-thrombolytic NIHSS 8-9 achieved favorable outcome. Weaker independent association was observed for blood glucose level and baseline diastolic blood pressure. CONCLUSIONS: As expected, NIHSS score and patient age showed the strongest association with final outcome in a subpopulation of patients having considerable post-thrombolytic neurological deficit. A relatively high proportion of patients with post-thrombolytic NIHSS 8-9 (10) achieved a favorable 3-month outcome without any further intervention.
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Fibrinolíticos/efectos adversos , Enfermedades del Sistema Nervioso/inducido químicamente , Accidente Cerebrovascular/tratamiento farmacológico , Resultado del Tratamiento , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Índice de Severidad de la EnfermedadRESUMEN
Myasthenia gravis (MG) is an autoantibody-mediated neuromuscular disease with an unpredictable clinical course. Serum free light chains (FLCs) have risen as a promising biomarker for MG, but their role in different subtypes of MG and in predicting disease progression is still uncharted. We investigated plasma from 58 generalized MG patients during post-thymectomy follow-up to determine κ and λ FLC and κ/λ ratio. In a subcohort of 30 patients, we examined the expression of 92 proteins associated with immuno-oncology using Olink. We further studied the ability of FLCs or proteomic markers to differentiate disease severity. Patients with late-onset MG (LOMG) displayed significantly higher mean κ/λ ratio than patients with early-onset MG (P = 0.004). Inducible T-cell co-stimulator ligand (ICOSLG), matrix metalloproteinase 7 (MMP7), hepatocyte growth factor (HGF), and arginase 1 (ARG1) were differentially expressed in MG patients compared to healthy controls. There were no significant associations between clinical outcomes and FLCs or the assayed proteins. In conclusion, an elevated κ/λ ratio suggests long-lasting aberrant clonal plasma cell function in LOMG. Immuno-oncology-related proteomic analysis showed alterations in immunoregulatory pathways. Our findings pinpoint the FLC ratio as a biomarker for LOMG and call for further investigation of the immunoregulatory pathways in MG.
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Miastenia Gravis , Proteómica , Humanos , Miastenia Gravis/diagnóstico , Cadenas Ligeras de Inmunoglobulina , Biomarcadores , Autoanticuerpos , Cadenas kappa de Inmunoglobulina , Cadenas lambda de InmunoglobulinaRESUMEN
OBJECTIVES: To study the safety and efficacy of vitamin D3 as an add on therapy to interferon ß-1b (IFNB) in patients with multiple sclerosis (MS). METHODS: 1 year, double blind, placebo controlled, randomised study in 66 MS patients. The primary outcomes were T2 burden of disease (BOD) on MRI scans, proportion of patients with serum levels of 25-hydroxyvitamin D (25(OH)D) ≥85 nmol/l or intact parathyroid hormone (PTH) ≤20 ng/l, and number of adverse events. Secondary outcomes were number of MRI enhancing T1 lesions and new T2 lesions, annual relapse rate, changes in the Expanded Disability Status Scale score, timed 25 foot walk test and timed 10 foot tandem walk tests. RESULTS: Median change in BOD was 287 mm(3) in the placebo group and 83 mm(3) in the vitamin D group (p=0.105). Serum levels of 25(OH)D increased from a mean of 54 (range 19-82) nmol/l to 110 (range 67-163) nmol/l in the vitamin D group. 84% of patients reached a serum 25(OH)D level >85 nmol/l in the vitamin D group and 3% in the placebo group (p<0.0001). Patients in the vitamin D group showed fewer new T2 lesions (p=0.286) and a significantly lower number of T1 enhancing lesions (p=0.004), as well as a tendency to reduced disability accumulation (p=0.071) and to improved timed tandem walk (p=0.076). There were no significant differences in adverse events or in the annual relapse rate. CONCLUSION: Vitamin D3 add on treatment to IFNB reduces MRI disease activity in MS. TRIAL REGISTRATION NUMBER: EudraCT number 2007-001958-99 and ClinicalTrialsGov number NCT01339676.
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Adyuvantes Inmunológicos/uso terapéutico , Colecalciferol/uso terapéutico , Interferón beta/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Vitaminas/uso terapéutico , Adyuvantes Inmunológicos/administración & dosificación , Adolescente , Adulto , Encéfalo/patología , Colecalciferol/administración & dosificación , Colecalciferol/efectos adversos , Colecalciferol/farmacocinética , Método Doble Ciego , Quimioterapia Combinada/efectos adversos , Femenino , Humanos , Inyecciones Subcutáneas , Interferon beta-1b , Interferón beta/administración & dosificación , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Esclerosis Múltiple/patología , Neuroimagen/métodos , Hormona Paratiroidea/sangre , Recurrencia , Índice de Severidad de la Enfermedad , Vitamina D/análogos & derivados , Vitamina D/sangre , Vitaminas/administración & dosificación , Vitaminas/efectos adversos , Vitaminas/farmacocinética , CaminataRESUMEN
STUDY OBJECTIVE: The necessity for rapid administration of intravenous thrombolysis in patients with acute ischemic stroke may lead to treatment of patients with conditions mimicking stroke. We analyze stroke patients treated with intravenous thrombolysis in our center to characterize cases classified as stroke mimics. METHODS: We identified and reviewed all cases with a diagnosis other than ischemic stroke in our large-scale single-center stroke thrombolysis registry. We compared these stroke mimics with patients with neuroimaging-negative and neuroimaging-positive ischemic stroke results. RESULTS: Among 985 consecutive intravenous thrombolysis-treated patients, we found 14 stroke mimics (1.4%; 95% confidence interval 0.8% to 2.4%), 694 (70.5%) patients with neuroimaging-positive ischemic stroke results, and 275 (27.9%) patients with neuroimaging-negative ischemic stroke results. Stroke mimics were younger than patients with neuroimaging-negative or -positive ischemic stroke results. Compared with patients with neuroimaging-positive ischemic stroke results, stroke mimics had less severe symptoms at baseline and better 3-month outcome. No differences appeared in medical history or clinical features between stroke mimics and patients with neuroimaging-negative ischemic stroke results. None of the stroke mimics developed symptomatic intracerebral hemorrhage compared with 63 (9.1%) among patients with neuroimaging-positive ischemic stroke results and 6 (2.2%) among patients with neuroimaging-negative ischemic stroke results. CONCLUSION: Stroke mimics were infrequent among intravenous thrombolysis-treated stroke patients in this cohort, and their treatment did not lead to harmful complications.
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Accidente Cerebrovascular/diagnóstico , Terapia Trombolítica , Adulto , Anciano , Errores Diagnósticos/efectos adversos , Errores Diagnósticos/estadística & datos numéricos , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen/estadística & datos numéricos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/estadística & datos numéricos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: Cladribine tablets for adult patients with highly active relapsing multiple sclerosis (MS) have been available in Finland since 2018. Real-world data from different genetic and geographical backgrounds are needed to complement data from clinical trials. METHODS: We investigated the use of cladribine tablets in Finland in a non-interventional cohort study, based on real-world data from the nationwide Finnish MS registry. All eligible patients who had initiated treatment with cladribine tablets in 2018-2020 were included. Descriptive analyses for outcomes were conducted using summary statistics. Time-dependent endpoints were analyzed using cumulated events analysis based on 1-Kaplan-Meier estimates and curves. Subgroups were analyzed separately according to the number of previous disease-modifying therapies (DMTs) and the most common last preceding therapies. RESULTS: Data of 179 patients were analyzed. Median follow-up time was 19.0 months (interquartile range [IQR] 12.0-26.2). Of the 134 patients who were followed for at least 12 months, 112 patients (83.6%) remained relapse-free during follow-up. Mean annualized relapse rate (ARR) was 1.0 (standard deviation [SD] 0.89) at baseline, and 0.1 (SD 0.30) at follow-up. Patients with two or more previous DMTs had shorter time to first relapse (median 2.5 months, IQR 0.6-9.3) when compared to patients with 0-1 previous DMTs (median 11.4 months, IQR 8.7-13.1) (p=0.013). After excluding patients switching from fingolimod (n=33), a statistically significant difference in time to first relapse was no longer observed between the two groups (p=0.252). Adverse events (AEs) were reported in 30 patients (16.8%). The most frequent AE was headache (n=14, 7.8%). One patient (0.6%) died of cardiac arrest. Discontinuation of cladribine tablets was reported in nine patients (5.0%). CONCLUSION: The mean ARR observed in this cohort was similar to what has been reported in clinical trials. Approximately half of the patients had used two or more previous DMTs before cladribine tablets. These patients had a shorter time to first relapse when compared to patients with 0-1 previous DMTs, mostly driven by early relapses in patients switching from fingolimod.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Adulto , Cladribina/efectos adversos , Estudios de Cohortes , Clorhidrato de Fingolimod/efectos adversos , Finlandia/epidemiología , Humanos , Inmunosupresores/efectos adversos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/inducido químicamente , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Recurrencia , Sistema de Registros , ComprimidosRESUMEN
BACKGROUND AND PURPOSE: treating ischemic stroke with thrombolytic therapy is effective and safe, but limited data exist on its efficacy and safety in different etiologic subtypes. METHODS: patients with acute ischemic stroke treated with intravenous thrombolysis between 1995 and 2008 at our hospital were classified according to the Trial of ORG 10172 in Acute Stroke Treatment criteria based on diagnostic evaluation. Clinical outcome of the stroke subtypes by 3-month modified Rankin Scale was compared by multivariate logistic regression. A good outcome was defined as modified Rankin Scale ≤ 2. Symptomatic intracranial hemorrhage was defined according to both National Institute of Neurological Disorders and Stroke and European Cooperative Acute Stroke Study criteria. RESULTS: of the 957 eligible patients, 41% (389) had cardioembolisms, 23% (217) large-artery atherosclerosis, and 11% (101) small-vessel disease (SVD). A good outcome was more common in SVD than in the other subtypes. Patients with SVD were more often male (64% versus 54%), had a lower baseline National Institutes of Health Stroke Scale score, lower mortality rate, and experienced no symptomatic intracranial hemorrhage. Patients with SVD had a prior stroke more often (20% versus 11%), whereas hypertension, diabetes, hypercholesterolemia, and transient ischemic attacks were equally distributed in all subtypes. Patients with SVD had a better outcome even after adjusting for baseline National Institutes of Health Stroke Scale and glucose level, age, and hyperdense artery sign (OR, 1.81; 1.01 to 3.23). In the adjusted multivariate model, other etiologic groups showed no significant correlation to good outcome. CONCLUSIONS: patients with SVD were spared from bleeding complications and had the best outcome even after adjustment for confounding factors.
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Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/terapia , Terapia Trombolítica , Anciano , Anciano de 80 o más Años , Aterosclerosis/complicaciones , Aterosclerosis/mortalidad , Aterosclerosis/terapia , Complicaciones de la Diabetes/mortalidad , Complicaciones de la Diabetes/terapia , Embolia/complicaciones , Embolia/mortalidad , Embolia/terapia , Femenino , Finlandia/epidemiología , Humanos , Hipercolesterolemia/complicaciones , Hipercolesterolemia/mortalidad , Hipercolesterolemia/terapia , Hipertensión/complicaciones , Hipertensión/mortalidad , Hipertensión/terapia , Hemorragias Intracraneales/etiología , Hemorragias Intracraneales/mortalidad , Hemorragias Intracraneales/terapia , Ataque Isquémico Transitorio/complicaciones , Ataque Isquémico Transitorio/mortalidad , Ataque Isquémico Transitorio/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios RetrospectivosRESUMEN
BACKGROUND: A part of ischemic stroke patients score 0 on the National Institutes of Health Stroke Scale (NIHSS) within 24 h following thrombolysis. Their clinical characteristics and long-term outcome are poorly studied. We report a single-center assessment of such patients. METHODS: The cohort comprises 874 consecutive patients from the Helsinki Stroke Thrombolysis Registry, out of whom 113 scored 0 on 24-hour NIHSS. We analyzed their baseline demographic, clinical and radiological characteristics and 3-month outcome (modified Rankin Scale, mRS). Associations between the study parameters were tested by multivariate analysis. RESULTS: Patients with a 24-hour NIHSS score = 0 (n = 113) were younger than the rest of the population (n = 761; median: 65.6 vs. 71.5 years; p < 0.001), their NIHSS score on admission was lower (median: 5 vs. 10; p < 0.001), as was their glucose level (median: 6.2 vs. 6.7 mmol/l; p = 0.02). The onset-to-treatment time was similar in both groups (median: 120 vs. 115 min; p = 0.89). Patients with a 24-hour NIHSS score = 0 more often achieved an excellent outcome (mRS scores: 0-1; 81 vs. 31%; p < 0.001) and had lower mortality (1.8 vs. 11.8%; p < 0.01). One third of these patients had a brain infarction visible on 24-hour imaging. Lower baseline NIHSS score and younger age were independently associated with 24-hour NIHSS score = 0, which, in turn, was independently associated with excellent 3-month outcome. CONCLUSIONS: Patients with an NIHSS score = 0 at 24 h following thrombolysis are younger, have milder symptoms and have a lower glucose level on admission. They achieve more often excellent outcome and lower mortality. Still, 8% of them required help in daily activities or were dead at 3 months (mRS scores: 3-6).
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Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica , Activador de Tejido Plasminógeno/administración & dosificación , Factores de Edad , Anciano , Glucemia/análisis , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidad , Evaluación de la Discapacidad , Femenino , Finlandia , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Admisión del Paciente , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Treating hyperglycemia in acute ischemic stroke may be beneficial, but knowledge on its prognostic value and optimal target glucose levels is scarce. We investigated the dynamics of glucose levels and the association of hyperglycemia with outcomes on admission and within 48 h after thrombolysis. METHODS: We included 851 consecutive patients with acute ischemic stroke treated with intravenous thrombolysis in the Helsinki University Central Hospital during 1998-2008. Outcome measures were unfavorable 3- month outcome (3-6 on the modified Rankin Scale), death, and symptomatic intracerebral hemorrhage (sICH) according to NINDS criteria. Hyperglycemia was defined as a blood glucose level of ≥8.0 mmol/l. Four groups were identified based on (a) admission and (b) peak glucose levels 48 h after thrombolysis: (1) persistent normoglycemia (baseline plus 48-hour normoglycemia), (2) baseline hyperglycemia (48-hour normoglycemia), (3) 48-hour hyperglycemia (baseline normoglycemia), and (4) persistent hyperglycemia (baseline plus 48-hour hyperglycemia). RESULTS: 480 (56.4%) of our patients (median age 70 years; onset-to-needle time 199 min; National Institutes of Health Stroke Scale score 9), had persistent normoglycemia, 59 (6.9%) had baseline hyperglycemia, 175 (20.6%) had 48-hour hyperglycemia, while persistent hyperglycemia appeared in 137 (16.1%) patients. Persistent and 48-hour hyperglycemia independently predicted unfavorable outcome [odds ratio (OR) = 2.33, 95% confidence interval (CI) = 1.41-3.86, and OR = 2.17, 95% CI = 1.30-3.38, respectively], death (OR = 6.63, 95% CI = 3.25-13.54, and OR = 3.13, 95% CI = 1.56-6.27, respectively), and sICH (OR = 3.02, 95% CI = 1.68-5.43, and OR = 1.89, 95% CI = 1.04-3.43, respectively), whereas baseline hyperglycemia did not. CONCLUSIONS: Hyperglycemia (≥8.0 mmol/l) during 48 h after intravenous thrombolysis of ischemic stroke is strongly associated with unfavorable outcome, sICH, and death.
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Glucemia/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Hiperglucemia/sangre , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica , Anciano , Glucemia/efectos de los fármacos , Isquemia Encefálica/sangre , Isquemia Encefálica/mortalidad , Distribución de Chi-Cuadrado , Femenino , Fibrinolíticos/efectos adversos , Finlandia , Humanos , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/mortalidad , Hipoglucemiantes/uso terapéutico , Hemorragias Intracraneales/inducido químicamente , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/mortalidad , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/mortalidad , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The effect of comorbidities on the prognosis of myasthenia gravis (MG) remains unclear. In particular, the role of other autoimmune diseases (AD) is controversial. METHODS: In this retrospective single-center cohort study, we investigated 154 consecutive generalized thymectomized MG patients, with a mean follow-up time of 8.6 (±5.0) years post-thymectomy. Comorbidities diagnosed at any timepoint were retrieved from medical records and Charlson comorbidity index (CCI) scores were calculated. Patients were categorized into subgroups MG alone (n = 45) and MG with any comorbidity (n = 109); the latter was further categorized into MG with other ADs (n = 33) and MG with non-AD comorbidities (n = 76). The endpoints analyzed were complete stable remission (CSR), minimal need for medications, and need for in-hospital treatments. RESULTS: CSR was more frequent in MG alone than in MG with any comorbidity group (26.7% vs 8.3%, p = 0.004). Minimal need for medication was reached more often in the MG alone than in the MG with non-AD comorbidities group (p = 0.047). Need for in-hospital treatments was lower in the MG alone group than in MG patients with any comorbidity (p = 0.046). Logistic regression analysis revealed that lower CCI scores increased the likelihood of CSR (p = 0.033). Lower CCI scores were more prevalent both in patients with minimal need for medication and in patients who did not need in-hospital treatments (p < 0.001). CONCLUSIONS: Patients with generalized MG and comorbidities have a poorer prognosis than patients with MG alone during almost 9 years follow-up after thymectomy. AD comorbidities appeared not to translate into a higher risk compared to other comorbidities.
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Miastenia Gravis , Timectomía , Estudios de Cohortes , Comorbilidad , Humanos , Miastenia Gravis/complicaciones , Miastenia Gravis/epidemiología , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Gelsolin amyloidosis (AGel amyloidosis) is a hereditary form of systemic amyloidosis featuring ophthalmological, neurological and cutaneous symptoms. Previous studies based mainly on patients' self-reporting have indicated that hearing impairment might also be related to the disease, considering the progressive cranial neuropathy characteristic for AGel amyloidosis. In order to deepen the knowledge of possible AGel amyloidosis-related hearing problems, a clinical study consisting of the Speech, Spatial and Qualities of Hearing Scale (SSQ) questionnaire, clinical examination, automated pure-tone audiometry and a speech-in-noise test was designed. RESULTS: Of the total 46 patients included in the study, eighteen (39%) had self-reported hearing loss. The mean scores in the SSQ were 8.2, 8.3 and 8.6 for the Speech, Spatial and Qualities subscales, respectively. In audiometry, the mean pure tone average (PTA) was 17.1 (SD 12.2) and 17.1 (SD 12.3) dB HL for the right and left ears, respectively, with no difference to gender- and age-matched, otologically normal reference values. The average speech reception threshold in noise (SRT) was - 8.2 (SD 1.5) and - 8.0 (SD 1.7) dB SNR for the right and left ears, respectively, which did not differ from a control group with a comparable range in PTA thresholds. CONCLUSION: Although a significant proportion of AGel amyloidosis patients experience subjective difficulties in hearing there seems to be no peripheral or central hearing impairment at least in patients up to the age of 60 years.