Intracranial Arachnoiditis and Hydrocephalus.

A 62-year-old man presented a diffuse and predominantly cisternal acute nonaneurysmal subarachnoid hemorrhage associated with hydrocephalus. An external ventricular drain was placed, followed by clinical deterioration after its removal. At this point, a heavily T2-weighted high-resolution sequence of a brain magnetic resonance imaging showed acute hydrocephalus recrudescence and multiple arachnoid adhesions in the supravermian and interpeduncular cisterns, creating a loculated/cystic appearance. The diagnosis of intracranial arachnoiditis was made. Intracranial arachnoiditis results from meningeal inflammation. Fibrosis and adhesions at the subarachnoid spaces may follow, restricting cerebrospinal fluid circulation, particularly at the cranial base. Hydrocephalus probably resulted from the combination of subarachnoid hemorrhage and extensive scaring at the basal cisterns, precluding transdural and transvenous cerebrospinal fluid efflux. Heavily T2-weighted high-resolution magnetic resonance imaging sequences allow an exquisite depiction of arachnoiditis, displaying obstructive cisternal membranes, and contribute to better etiologic assessment and management of hydrocephalus.

Inflammatory Activity and Treatment Response in Pediatric Compared to Adult Multiple Sclerosis: A Pilot, Retrospective and Observational Study of the First Year After Diagnosis.

INTRODUCTION: Pediatric-onset multiple sclerosis may contrast with adult-onset multiple sclerosis, in terms of disease activity. We aimed to determine differentiating features between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis, at diagnosis and after one year under disease modifying therapies, and analyse the attainment of the status of "No Evidence of Disease Activity" between groups. MATERIAL AND METHODS: We analyzed demographical, laboratory, clinical and imaging features of patients with relapsing-remitting multiple sclerosis diagnosed at our center, according to the McDonald's 2010 criteria, with ≥ 1 year under disease modifying therapies and with available magnetic resonance imaging scans at diagnosis and one year after disease modifying therapies initiation. Patients were paired according to gender and disease modifying therapies in use. "No Evidence of Disease Activity" status was assessed, and differences were studied. RESULTS: Fifteen pediatric-onset multiple sclerosis (aged ≥ 8 and < 18 years) and 15 adult-onset multiple sclerosis (≥ 18 and < 55 years) patients were recruited. We found a statistically significant difference in the number of T2 weighted image diffuse lesions/with poorly defined borders (p = 0.015). The mean expanded disability status scale score after one year under disease modifying therapies was lower in the pediatric-onset multiple sclerosis group (1.6 ± 0.8) compared to the adult-onset multiple sclerosis group (2.3 ± 0.8; p = 0.032). Nevertheless, no differences were found regarding the percentage of cases achieving "No Evidence of Disease Activity" in either group. DISCUSSION: Although there is an empirical impression about the difference in inflammatory activity between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis, it was not possible to corroborate it in our study. Nevertheless, this was an exploratory and retrospective analysis of a small sample of patients, identifying variables in which such differences appear to be most important. CONCLUSION: Extensive studies of children, adolescents and adults with multiple sclerosis will be needed to categorize the clinical and radiological differences that allow the identification of drug response biomarkers in the early stages of the disease.

Introdução: A esclerose múltipla de início em idade pediátrica pode contrastar com a esclerose múltipla de início na idade adulta, em termos de atividade da doença. Pretendemos determinar características diferenciadoras entre esclerose múltipla de início em idade pediátrica e esclerose múltipla de início na idade adulta ao diagnóstico e um ano após o início de terapêuticas modificadoras da doença e analisar o atingimento do estado de "Ausência de Evidência de Atividade de Doença". Material e Métodos: Analisámos as características demográficas, laboratoriais, clínicas e imagiológicas de doentes com esclerose múltipla surto-remissão diagnosticados no nosso centro, segundo os critérios de McDonald 2010, com ≥ 1 ano sob terapêuticas modificadoras de doença e com ressonâncias magnéticas disponíveis no diagnóstico e um ano após o início de terapêuticas modificadoras da doença. Os doentes foram emparelhados de acordo com o género e terapêuticas em uso. O estado de "Ausência de Evidência de Atividade de Doença" foi avaliado e as diferenças estudadas. Resultados: Quinze doentes com esclerose múltipla de início em idade pediátrica (≥ 8 e < 18 anos de idade) e 15 com esclerose múltipla de início na idade adulta (≥ 18 e < 55 anos de idade) foram recrutados para este estudo. Encontrámos uma diferença estatisticamente significativa no número de lesões difusas/com bordos mal definidos ponderadas em T2 (p = 0,015). A pontuação média da escala expandida de incapacidade após um ano sob a respetiva terapêutica modificadora de doença foi menor no grupo esclerose múltipla de início em idade pediátrica (1,6 ± 0,8) em comparação com o grupo esclerose múltipla de início na idade adulta (2,3 ± 0,8; p = 0,032). Ainda assim, não se encontraram diferenças relativamente à percentagem de casos alcançando "Ausência de Evidência de Atividade de Doença" em ambos os grupos. Discussão: Apesar de existir uma impressão empírica sobre uma diferença de atividade inflamatória entre a esclerose múltipla de início em idade pediátrica e a esclerose múltipla de início na idade adulta, não foi possível corroborá-la no nosso estudo. De qualquer modo, esta foi uma análise exploratória e retrospetiva de uma amostra pequena de doentes, em que identificámos as variáveis em que tais diferenças parecem ser mais importantes. Conclusão: Estudos alargados de crianças, adolescentes e adultos com esclerose múltipla serão necessários para categorizar as diferenças clínicas e radiológicas que permitam identificar biomarcadores de resposta a fármacos, em fases precoces da doença.

Oxidative stress assessment in sickle cell anemia patients treated with hydroxyurea.

Hydroxyurea (HU) is used as a therapy in sickle cell anemia (SCA). Many studies have established that HU improves patient quality of life by reducing symptoms. However, the effect of HU on erythrocytes is not well-described. We evaluated several parameters related to oxidative stress and total lipid content of erythrocytes in patients with SCA. The patient cohort consisted of 7 SCA patients treated with HU, 17 untreated SCA patients, and 15 healthy subjects. Erythrocytes from patients with SCA displayed increased oxidative stress relative to the control group, including higher thiobarbituric acid reactive substances (TBARS), Fe3+ content, and osmotic fragility, and decreased total cholesterol. We observed that treatment of SCA patients with HU increased Fe3+ content and activity of glutathione peroxidase, and decreased glutathione reductase activity, glutathione levels, total cholesterol, and phospholipid content comaperaded to patients untreated with HU. Thus, HU alters biochemical characteristics of erythrocytes; future studies will determine whether they are beneficial or not.

Influence of ACE I/D Polymorphism on Circulating Levels of Plasminogen Activator Inhibitor 1, D-Dimer, Ultrasensitive C-Reactive Protein and Transforming Growth Factor ß1 in Patients Undergoing Hemodialysis.

BACKGROUND: There is substantial evidence that chronic renal and cardiovascular diseases are associated with coagulation disorders, endothelial dysfunction, inflammation and fibrosis. Angiotensin-Converting Enzyme Insertion/Deletion polymorphism (ACE I/D polymorphism) has also be linked to cardiovascular diseases. Therefore, this study aimed to compare plasma levels of ultrassensible C-reactive protein (usCRP), PAI-1, D-dimer and TGF-ß1 in patients undergoing HD with different ACE I/D polymorphisms. METHODS: The study was performed in 138 patients at ESRD under hemodialysis therapy for more than six months. The patients were divided into three groups according to the genotype. Genomic DNA was extracted from blood cells (leukocytes). ACE I/D polymorphism was investigated by single polymerase chain reaction (PCR). Plasma levels of D-dimer, PAI-1 and TGF-ß1 were measured by enzyme-linked immunosorbent assay (ELISA), and the determination of plasma levels of usCRP was performed by immunonephelometry. Data were analyzed by the software SigmaStat 2.03. RESULTS: Clinical characteristics were similar in patients with these three ACE I/D polymorphisms, except for interdialytic weight gain. I allele could be associated with higher interdialytic weight gain (P = 0.017). Patients genotyped as DD and as ID had significantly higher levels of PAI-1 than those with II genotype. Other laboratory parameters did not significantly differ among the three subgroups (P = 0.033). Despite not reaching statistical significance, plasma levels of usCRP were higher in patients carrying the D allele. CONCLUSION: ACE I/D polymorphisms could be associated with changes in the regulation of sodium, fibrinolytic system, and possibly, inflammation. Our data showed that high levels of PAI-1 are detected when D allele is present, whereas greater interdialytic gain is associated with the presence of I allele. However, further studies with different experimental designs are necessary to elucidate the mechanisms involved in these associations.