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AIM: To evaluate the effectiveness of the ketogenic diet treatment in a cohort of patients with drug-resistant epilepsy with a mutation in the DEPDC5 gene. MATERIALS AND METHODS: We followed four paediatric patients with drug resistant DEPDC5-related epilepsy through a ketogenic diet (KD) treatment course. We analyzed the following parameters of their clinical profiles: past medical history, clinical characteristics of seizure morphology, EEG records pre- and post-KD treatment, the results of MRI head and neurological and psychological examinations (pre-treatment and throughout treatment course). We evaluated the effectiveness of previous therapeutic approaches and the current treatment with ketogenic diet alongside results of neuroimaging studies. Effect of KD on co-morbid behavioural and psychiatric symptoms, as well as adverse effects from KD were also assessed. RESULTS: In three patients, the introduction of the ketogenic diet resulted in the cessation of seizures, while in 1 patient with co-morbid cortical dysplasia, epileptic seizures of lesser severity returned after an initial seizure-free period of several weeks. Further, 1 patient was able to transition to a KD-only treatment regimen. The remaining patients were able to reduce the number of antiseizure medicine (ASM) to a monotherapy. In all cases we observed improvements in EEG results. Our cohort included one patient whose MRI head showed cortical dysplasia. However, no patients demonstrated any neurological signs in neurological examination. Psychological examination showed normal intellectual development in all patients, although behavioral disorders and difficulties at school were observed. The introduction of KD treatment correlated with improvement in school performance and improved behavioral regulation. No clinically significant adverse events were observed. CONCLUSIONS: KD seems to be both effective and well tolerated in young patients with DEPDC5-related epilepsy, both as a monotherapy and as an adjunct to ASM. We recommend an early adoption of this therapeutic approach in this patient demographic. Our results demonstrate that the positive effects of KD treatment encompass improvements in general functioning, particularly in the context of school performance and behavior, in addition to the achievement of good seizure control.
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Dieta Cetogênica , Epilepsia Resistente a Medicamentos , Epilepsia , Malformações do Desenvolvimento Cortical , Criança , Humanos , Dieta Cetogênica/métodos , Resultado do Tratamento , Estudos Retrospectivos , ConvulsõesRESUMO
Missense variants in the synaptic vesicle glycoprotein SV2A gene have been previously found in a few individuals with epilepsy. Adverse reaction to levetiracetam in individuals with various variants of this gene has recently been described. Here, we report on a family with several members affected by epilepsy. In affected members of this family, we identified a variant in the SV2A gene (NM_014849.5: c.1978 G>A, p.(Gly660Arg). This family case further supports the role of the SV2A gene in autosomal dominant epilepsy. It provides new information on the course of epilepsy in people with variants in the SV2A gene who have never been treated with SV2A agonists and specific neurodevelopmental features of this syndrome.
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Artrogripose , Epilepsia , Humanos , Artrogripose/induzido quimicamente , Epilepsia/tratamento farmacológico , Epilepsia/genética , Epilepsia/induzido quimicamente , Levetiracetam/uso terapêutico , Glicoproteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Variação GenéticaRESUMO
BACKGROUND: Epidemiologic data on pediatric-onset multiple sclerosis (POMS) in Central and Eastern Europe are limited. The aim of this study was to determine the incidence, prevalence and the clinical features of POMS in Poland. METHODS: Registry-based retrospective study was conducted among Polish children population (age ≤ 18 years), between 1 January 2010 and 31 December 2019. A total of 329 pediatric or juvenile patients fulfilled the International Pediatric MS Study Group (IPMSSG) criteria for MS, reported to the Polish Multiple Sclerosis Registry, were considered for estimation of age- and sex-specific prevalence (per 100,000 persons), and incidence rates (per 100,000 person-years). The demographic data, clinical presentation and treatment strategies also were investigated. RESULTS: On December 31, 2019 in the database were collected data of 329 patients up to 18 years with POMS diagnosis (101 boys and 228 girls; mean age 15.3 ± 3.8 years). The age-adjusted prevalence standardized to the European Standard Population was 5.19/100,000 (95% confidence interval (CI), 4.64-5.78). A significantly higher prevalence was recorded in girls (7.41; 95% CI, 6.48-8.44) than in boys (3.08; 95% CI, 2.50-3.74; P<0.001). The mean annual standardized incidence in Poland between 2015 - 2019 was 0.77 (95%CI, 0.45-1.02) per 100,000 person-years. The highest overall standardized incidence 1.06 (95%CI, 0.82-1.34) was noted in 2018. Most of patients (95.7%) had relapsing-remitting disease with polysymptomatic onset in one-thirds of the cases, and 82.3% were treated with disease-modifying drugs. Family history of MS was reported in 26 cases (7.9%). CONCLUSION: In this first report of registry-based study from Poland an increasing prevalence and incidence of POMS was found during the last years. This temporal trend corroborate the findings of studies conducted elsewhere.
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Esclerose Múltipla , Adolescente , Adulto , Criança , Feminino , Humanos , Incidência , Masculino , Esclerose Múltipla/epidemiologia , Polônia/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Adulto JovemRESUMO
Background. Paediatric-onset MS (POMS) has a unique clinical profile compared to the more prevalent adult-onset MS. For this study, we aimed to determine the demographic and clinical characteristics of POMS in Poland as well as addressing some of its epidemiological aspects. Methods. A retrospective study was conducted based on the Polish Multiple Sclerosis Registry, considering a population of children and adolescents with MS (age ≤ 18 years). Data were collected by all 13 centres across Poland specializing in diagnosing and treating POMS. The actual course of the disease and its clinical properties were compared between child (≤12 years) and juvenile (>12 years) patients. MS onset and its prevalence were assessed at the end of 2019, stratified by age range. Results. A total of 329 paediatric or juvenile patients (228 girls, 101 boys) with a clinically definite diagnosis of MS, in conformity with the 2017 McDonald Criteria, were enrolled. For 71 children (21.6%), the first symptoms appeared before the age of 12. The female: male ratio increased with age, amounting to 1:1 in the ≤12 years group and to 2.9:1 in the >12 years group. In most cases, the disease had multi-symptomatic onset (31.3%), and its course was mostly of a relapsing−remitting character (95.7%). The initial Expanded Disability Status Score for both groups was 1.63 ± 1.1, whereas the annual relapse rate was 0.84 during the first 2 years. The time between the onset of symptoms and diagnosis was longer in the younger patients (8.2 ± 4.2 vs. 4.6 ± 3.6 months; p < 0.005). On 31 December 2019, the age-adjusted prevalence standardized to the European standard population was 5.19/100,000 (95% CI, 4.64−5.78). Significantly higher prevalence was noted in the 13−18 years group (7.12; 95% CI, 6.64−7.86) than in the 9−12 years group (3.41; 95% CI, 2.98−3.86) and the <9 years group (0.56; 95% CI, 0.46−0.64; p < 0.001). Conclusion. POMS commencing at the age of ≤12 years is rare, differing significantly from the juvenile-onset and adult MS in terms of clinical characteristics, course, and incidence, as stratified by gender.
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BACKGROUND: The severity of neurological deficits arising from ischemic stroke may be related to serum redox homeostasis. The aim of this study was to estimate the effect of serum paraoxonase (PON), arylesterase (ARE) activities and conjugated dienes (CD) on patient outcome during a 1-year follow-up period. METHODS: The study included 468 consecutive ischemic stroke patients (251 males, 217 females) with an average age of 67.5 ± 12.4 years. Clinical evaluation was based on vital signs, National Institutes of Health Stroke Scale (NIHSS) scored at the time of admission and on the 7th day after stroke, as well as modified Rankin scale (mRS) and Barthel index (BI) scored at 30, 90, 180 and 360 days after stroke onset. Serum PON, ARE activities and CD concentration were measured with the use of spectrophotometric methods. RESULTS: Serum PON activity alone correlated directly with a favorable outcome during a 3-month observation period. Serum ARE activity correlated directly only with the mRS score in a 1-year observation. PON/ARE ratio showed the strongest direct correlation with favorable stroke outcome expressed by BI and inverse correlation with mRS as compared to serum PON or ARE activities assessed alone. PON/ARE affected the NIHSS score on admission (rS = -0.119, p = 0.014) and on the 7th day after stroke (rS = 0.120, p = 0.015); it also showed an association with the BI and mRS on the 30th (rS = 0.145, p = 0.007 and rS = -0.098, p = 0.049, respectively), 90th (rS = 0.147, p = 0.009, rS = -0.133, p = 0.008, respectively), as well as 180th, and 360th day after stroke. We did not find correlations between the serum CD concentration and stroke outcome. CONCLUSION: The PON/ARE ratio is an important predictor of ischemic stroke outcome and can be used in clinical practice rather than evaluating either PON or ARE activity alone.
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Arildialquilfosfatase/sangue , Hidrolases de Éster Carboxílico/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Idoso , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Índice de Gravidade de DoençaRESUMO
UNLABELLED: Cigarette smoking is one of most important modifiable risk factors of stroke. Lipids peroxidation remains crucial among pathomechanisms leading to increased risk of stroke in tobacco smokers. AIM OF THE STUDY: To evaluate the effect of cigarette smoking on the activity of paraoxonase and arylesterase as enzymes involved in protection against oxidation of low-density lipoproteins. We have included in the study 431 subsequent stroke patients hospitalized in Department of Neurology in Poznan in a period from February 2007 to May 2008. The control group consisted of 16 healthy, nonsmoking volunteers. The activity of paraoxonase (PON) and arylesterase (ARE) in patients' sera was estimated by spectrophotometric methods. All patients admitted to emergency room underwent clinical examination. General examination, neurological examination and clinimetric assessment with the use of GCS (Glasgow Coma Scale) and NIHSS (National Institute of Health Stroke Scale) scales were performed. RESULTS: The group of ischemic stroke patients consisted of 26.7% current smokers, 31.3%--ex-smokers, and 42% never-smokers. Among patients with hemorrhagic transformation of ischemic stroke 13.6 % actively smoked cigarettes, 22.7% were ex-smokers, and 63.7%--never-smokers. The statistical analysis of age of patients in all studied groups showed the younger onset of stroke in smokers (p < 0.0001). The activity of arylesterase was significantly disturbed by cigarette smoking in patients with ischemic stroke. In smokers with ischemic stroke ARE activity correlated negatively with number of cigarettes smoked daily (r = -0.2133; p = 0.0322). We have showed positive correlation of duration of smoking with ARE activity (r = 0.2573; p = 0.0239). In non-smoking ischemic stroke patients PON activity increased significantly (p < 0.01) comparing to controls. Tobacco smoking caused impairment of enzymatic antioxidant mechanisms related to paraoxonase activity, because there was no significant (p > 0.05) up-regulation of PON activity in smokers with ischemic stroke. The activity of arylesterase is modified by tobacco smoking in ischemic stroke patients. Smoking causes disturbances in paraoxonase--associated enzymatic antioxidant effects in ischemic stroke patients. Abnormalities of activities of antioxidant enzymes may cause earlier onset of stroke in tobacco smokers.
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Arildialquilfosfatase/sangue , Hidrolases de Éster Carboxílico/sangue , Fumar/sangue , Fumar/epidemiologia , Acidente Vascular Cerebral/enzimologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Idade de Início , Idoso , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Interferon beta (IFNb) preparations are commonly used as first-line therapy in relapsing-remitting multiple sclerosis (RRMS). They are, however, characterized by limited efficacy, partly due to the formation of anti-IFNb antibodies in patients.In this pilot study, we assessed with the ELISA method the presence of the binding antibodies (BAbs) against interferon beta after 2 years of therapy with subcutaneous interferon beta 1a (Rebif) in 49 RRMS patients. Antibody levels were established again within 1 year after treatment withdrawal. We used 3 interferons that are commercially available for MS therapy, namely Avonex (Biogen Idec Limited), Rebif (Merck Serono), and Betaferon (Bayer Pharma AG), as antigens.BAbs reacting with Rebif were found in 24.4% to 55% of patients, depending on the units of their expression. The levels of anti-Rebif antibodies remained high in 8 patients and in 4 patients they dropped significantly. Strong correlations were obtained in all assays (anti-Rebif-anti-Avonex, anti-Rebif-anti-Betaferon, and anti-Betaferon-anti-Avonex) and the existence of cross-reactivity in the formation of antibodies against all the tested formulations of interferon beta was confirmed. The levels of BAbs remain significant in the clinical context, and their assessment is the first choice screening; however, methods of BAbs evaluation can be crucial for further decisions. More studies are needed to confirm our results; specifically it would be of interest to evaluate methods of neutralizing antibodies identification, as we only assessed the binding antibodies. Nevertheless, our results support the concept that in interferon nonresponders, that are positive for binding antibodies, switching the therapy to alternative disease-modifying agent (for example glatiramer acetate, fingolimod, or natalizumab) is justified, whereas the switch to another interferon formulation will probably be of no benefit.
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Anticorpos/imunologia , Interferon beta-1a/imunologia , Interferon beta-1a/uso terapêutico , Interferon beta-1b/imunologia , Interferon beta-1b/uso terapêutico , Interferon beta/imunologia , Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/imunologia , Adulto , Reações Cruzadas , Feminino , Humanos , Masculino , Projetos Piloto , Estudos ProspectivosRESUMO
INTRODUCTION: Chronic venous disease is a group of symptoms caused by functional and structural defects of the venous vessels. One of the most common aspects of this disease is the occurrence of varicose veins. There are many ways of prevention and treatment of varicose veins, but in Poland the leading one is still surgery. As in every medical procedure there is the possibility of some complications. One of them is deep vein thrombosis (DVT). The diagnosis of DVT can be difficult, especially when access to a specialist is limited, such as in case of rural patients. The aim of the study. The aim of the study was estimation of the influence of LMWH primary prophylaxis on the formation of postoperative DVT, as well as sensitivity and specificity of clinical examination and D-dimer value in diagnosis of postoperative DVT in women. MATERIALS AND METHODS: The study was conducted in a group of 93 women operated on in the Department of General, Vascular Surgery and Angiology at the Karol Marcinkowski University of Medical Sciences in Poznan, Poland. The patients had undergone a varicose vein operation and were randomly divided into two groups: A - 48 women receiving LMWH during two days of the perioperative period, B - 45 women receiving LMWH during seven days of the perioperative period. RESULTS: There was no significant difference in the postoperative DVT complications in both groups. The value of D-dimer > 0.987 mcg/ml and swelling > 1.5 cm of shin (in comparison to the preoperative period) plays a significant role in diagnosis of DVT. CONCLUSIONS: The extended primary prophylaxis with LMWH does not affect the amount or quality of thrombotic complications after varicose vein operation. If the DVT occurs, the evaluation of the D - dimer and careful clinical examination can be a useful method for its diagnosis.
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Anticoagulantes/uso terapêutico , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Heparina de Baixo Peso Molecular/uso terapêutico , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Varizes/cirurgia , Trombose Venosa/diagnóstico , Trombose Venosa/prevenção & controle , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Polônia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , População Rural , Varizes/terapia , Trombose Venosa/etiologiaRESUMO
OBJECTIVE: To evaluate the significance of circulating tight-junction (TJ) proteins as predictors of hemorrhagic transformation (HT) in ischemic stroke patients. METHODS: We examined 458 consecutive ischemic stroke patients, 7.2% of whom had clinically evident HT. None of the patients was treated with thrombolytic drugs. Serum levels of standard markers of blood-brain barrier (BBB) breakdown (S100B, neuron-specific enolase), TJ proteins (occludin [OCLN], claudin 5 [CLDN5], zonula occludens 1 [ZO1]), and molecules involved in BBB disintegration (matrix metalloproteinase 9 and vascular endothelial growth factor [VEGF]) were assessed upon admission to the emergency department. A clinical deterioration caused by HT (cdHT) was defined as an increase of ≥4 points in the NIH Stroke Scale score in combination with a visible HT on a CT scan performed immediately after the onset of new neurologic symptoms. RESULTS: Patients with cdHT had higher concentrations of OCLN, S100B, and the CLDN5/ZO1 ratio, and a lower level of VEGF than those without cdHT. CLDN5 levels also correlated with cdHT occurrence when estimated within 3 hours of stroke onset. We also demonstrated correlations between the levels of circulating TJ molecules and the level of S100B, which is a previously established marker of BBB disruption. CONCLUSIONS: Analyzing serum levels of TJ proteins, like CLDN5, OCLN, and CLDN5/ZO1 ratio, as well as S100B and VEGF, is an effective way to screen for clinical deterioration caused by HT in ischemic stroke patients, both within and after the IV thrombolysis time window.