Exploratory study of blood biomarkers in patients with post-stroke epilepsy.

INTRODUCTION: In addition to clinical factors, blood-based biomarkers can provide useful information on the risk of developing post-stroke epilepsy (PSE). Our aim was to identify serum biomarkers at stroke onset that could contribute to predicting patients at higher risk of PSE. PATIENTS AND METHODS: From a previous study in which 895 acute stroke patients were followed-up, 51 patients developed PSE. We selected 15 patients with PSE and 15 controls without epilepsy. In a biomarker discovery setting, 5 Olink panels of 96 proteins each, were used to determine protein levels. Biomarkers that were down-regulated and overexpressed in PSE patients, and those that showed the strongest interactions with other proteins were validated using an enzyme-linked immunosorbent assay in samples from 50 PSE patients and 50 controls. A ROC curve analysis was used to evaluate the predictive ability of significant biomarkers to develop PSE. RESULTS: Mean age of the PSE discovery cohort was 68.56 ± 15.1, 40% women and baseline NIHSS 12 [IQR 1-25]. Nine proteins were down-expressed: CASP-8, TNFSF-14, STAMBP, ENRAGE, EDA2R, SIRT2, TGF-alpha, OSM and CLEC1B. VEGFa, CD40 and CCL4 showed greatest interactions with the remaining proteins. In the validation analysis, TNFSF-14 was the single biomarker showing statistically significant downregulated levels in PSE patients (p = 0.006) and it showed a good predictive capability to develop PSE (AUC 0.733, 95% CI 0.601-0.865). DISCUSSION AND CONCLUSION: Protein expression in PSE patients differs from that of non-epileptic stroke patients, suggesting the involvement of several different proteins in post-stroke epileptogenesis. TNFSF-14 emerges as a potential biomarker for predicting PSE.

Epileptiform electroencephalogram discharges increase seizure recurrence risk in patients with acute symptomatic seizure due to a structural brain lesion.

OBJECTIVE: The risk factors for seizure recurrence after acute symptomatic seizure due to a structural brain lesion are not well established. The aim of this study was to analyze possible associations between demographic, clinical, and electroencephalographic variables and epilepsy development in patients with acute symptomatic seizure due to an acute structural brain lesion. METHODS: We designed an observational prospective study of patients with acute symptomatic seizure due to an acute structural brain lesion (hemorrhagic stroke, ischemic stroke, traumatic brain injury, or meningoencephalitis) who underwent EEG during their initial admission between January 2015 and January 2020. We analyzed prospectively recorded demographic, clinical, electroencephalographic (EEG), and treatment-related variables. All variables were compared between patients with and without seizure recurrence during 2 years of follow up. RESULTS: We included 194 patients (41.2 % women; mean [SD] age, 57.3 [15.8] years) with acute symptomatic seizure due to an acute structural brain lesion. They all underwent EEG during admission and were followed for at least 2 years. The identifiable causes were hemorrhagic stroke (44.8 %), ischemic stroke (19.5 %), traumatic brain injury (18.5 %), and meningoencephalitis (17 %). Fifty-six patients (29 %) experienced a second seizure during follow-up. Seizure recurrence was associated with epileptiform discharges on EEG (52% vs 32 %; OR 2.3 [95 % CI, 1.2-4.3], p = 0.008) and onset with status epilepticus (17% vs 0.05 %, OR 4.03 [95 % CI 1.45-11.2], p = 0.009). CONCLUSIONS: Epileptiform discharges on EEG and status epilepticus in patients with acute symptomatic seizure due to an acute structural brain lesion are associated with a higher risk of epilepsy development.

Prevalence of Radiological Chronic Pancreatitis and Exocrine Pancreatic Insufficiency in Patients with Decompensated Liver Disease: Is Fecal Elastase Useful in This Setting?

Chronic alcohol consumption is a well-known etiological factor for both chronic pancreatitis (CP) and liver cirrhosis. However, there is discussion over how often these two entities are present together in the same patient. The main goal of our study is to establish the prevalence of CP and low fecal elastase (FE-1) in patients with decompensated liver disease (DLD). In addition, we aim to identify the demographic, epidemiological and clinical factors associated with EPI and CP in patients with decompensated liver cirrhosis. This was an observational single-center study including 119 consecutive patients hospitalized for acute decompensation of cirrhosis, mostly of alcoholic etiology. Patients underwent computed tomography (CT) or magnetic resonance imaging (MRI) to assess the radiological features of CP. We also performed two FE-1 tests and complete blood tests to assess the presence of exocrine pancreatic insufficiency (EPI) and nutritional status, including micronutrients. The results of our study show that 32 patients (26.9%) had low fecal elastase suggesting EPI and 11 (9.2%) had CP. Patients meeting radiological CP criteria had lower FE-1 than patients without CP. There were no statistically significant differences in micronutrient deficiencies according to the presence of CP or not. Likewise, we did not find any statistically significant differences in micronutrient deficiencies among patients with normal and low FE-1 indicative of EPI. FE-1 alone may not be suitable for assessing EPI in patients with acute DLD. Detecting co-existing pancreatic disease may be important in a subset of patients with DLD, when the FE-1 levels are significantly low, potentially suggestive of a pancreatic anomaly. Moreover, the clinical manifestations of EPI and CP are not useful in detecting CP in DLD patients. Likewise, CP cannot explain all causes of EPI in these patients.

Psychogenic nonepileptic seizures: The effect of accurate diagnosis on cognition.

OBJECTIVE: Much remains to be elucidated about the cognitive profile of patients with psychogenic nonepileptic seizures (PNES) and about how this changes over time and compares to that of patients with epilepsy. The aim of this study was to study the neuropsychological profile of patients with PNES and an age-matched group of patients with temporal lobe epilepsy (TLE) during admission to a video electroencephalography monitoring unit (VEMU) and 1 year after discharge. METHODS: Patients diagnosed with PNES or TLE at a VEMU were prospectively recruited. Neuropsychological, demographic, clinical, and treatment variables were collected at baseline and 1 year. To minimize multiple comparisons, scores from different cognitive tests were computed for attention and psychomotor speed, verbal memory, visual memory, language, and executive function. A global cognitive impairment index (GCII) was also created. Post hoc analyses were conducted to identify clinical variables that might mediate the differences observed in cognition over time between the groups. These included seizure frequency, number of antiseizure medication (ASM), number of psychotropic drugs, depression, and quality of life. RESULTS: We studied 24 patients with PNES and 24 patients with TLE. The groups performed similarly in the baseline neuropsychological tests. There was a significant time (baseline to 1-year follow-up) by group (PNES vs TLE) interaction for the GCII (p = 0.006), language (p = 0.04), and executive function (p = 0.013), with PNES patients showing improvement and TLE patients remaining stable. The time by group interaction for attention and psychomotor speed showed a trend toward significance (p = 0.056), Reduction in number of ASM was associated with improved cognition in PNES patients at 1 year. CONCLUSION: PNES patients showed improved cognition at 1 year of follow-up, particularly in language and executive functions. This finding shows the potential benefits of an early, accurate diagnosis, which range from improved cognition to better management.

Insomnia Symptoms in Patients With Substance Use Disorders During Detoxification and Associated Clinical Features.

Background: Insomnia is highly prevalent in patients with substance use disorders (SUD), and it has been related to a worse course of addiction. Insomnia during detoxification in a hospital has not been adequately studied. This study aims to compare sociodemographic, clinical, and psychopathological characteristics of SUD patients undergoing a detoxification program, by comorbidity and insomnia symptoms. Methodology: We recruited 481 patients who received pharmacological and psychotherapeutic treatment for detoxification. They were evaluated through semi-structured interviews, standardized questionnaires, and a specific sleep log. A bivariate and multivariate analysis of the data was performed. Results: Insomnia was reported by 66.5% patients, with sleep-maintenance insomnia the most frequent issue, followed by early morning awakening and sleep-onset insomnia. Patients with alcohol use disorder and cannabis use disorder had higher prevalence of sleep-onset insomnia. Patients with cocaine and heroin use disorder had higher prevalence of sleep-maintenance insomnia. Independent factors that allowed the identification of insomnia symptoms included being female (OR: 3.43), polysubstance use (OR: 2.85), comorbid anxiety disorder (OR: 2.02), and prior admission for detoxification (OR: 1.22). Conclusions: Insomnia symptoms are very prevalent in patients admitted for detoxification. The diagnosis and therapeutic strategies for the insomnia symptoms should be improved, especially in women and in patients with greater addiction severity and with anxiety disorders.

Blood biomarkers predictive of epilepsy after an acute stroke event.

OBJECTIVE: Blood biomarkers have not been widely investigated in poststroke epilepsy. In this study, we aimed to describe clinical factors and biomarkers present during acute stroke and analyze their association with the development of epilepsy at long term. METHODS: A panel of 14 blood biomarkers was evaluated in patients with ischemic and hemorrhagic stroke. Biomarkers were normalized and standardized using Z-scores. Stroke and epilepsy-related variables were also assessed: stroke severity, determined by National Institutes of Health Stroke Scale (NIHSS) score, stroke type and cause, time from stroke to onset of late seizures, and type of seizure. Multiple Cox regression models were used to identify clinical variables and biomarkers independently associated with epilepsy. RESULTS: From a cohort of 1115 patients, 895 patients were included. Mean ± standard deviation (SD) age was 72.0 ± 13.1 years, and 57.8% of patients were men. Fifty-one patients (5.7%) developed late seizures, with a median time to onset of 232 days (interquartile range [IQR] 86-491). NIHSS score ≥8 (P < .001, hazard ratio [HR] 4.013, 95% confidence interval [CI] 2.123-7.586) and a history of early onset seizures (P < .001, HR 4.038, 95% CI 1.802-9.045) were factors independently associated with a risk of developing epilepsy. Independent blood biomarkers predictive of epilepsy were high endostatin levels >1.203 (P = .046, HR 4.300, 95% CI 1.028-17.996) and low levels of heat shock 70 kDa protein-8 (Hsc70) <2.496 (P = .006, HR 3.795, 95% CI 1.476-9.760) and S100B <1.364 (P = .001, HR 2.955, 95% CI 1.534-5.491). The risk of epilepsy when these biomarkers were combined increased to 17%. The area under the receiver-operating characteristic (ROC) curve of the predictive model was stronger when clinical variables were combined with blood biomarkers (74.3%, 95% CI 65.2%-83.3%) than when they were used alone (68.9%, 95% CI 60.3%-77.6%). SIGNIFICANCE: Downregulated S100B and Hsc70 and upregulated endostatin may assist in prediction of poststroke epilepsy and may provide additional information to clinical risk factors. In addition, these data are hypothesis-generating for the epileptogenic process.

Clinical predictors of adverse events during continuous video-EEG monitoring in an epilepsy unit.

Patients admitted to epilepsy monitoring units (EMUs) for diagnostic and presurgical evaluation have an increased risk of seizure-related injury, particularly in the many cases in which medication is withdrawn. The purpose of this study was to assess the prevalence of adverse events (AEs) in this setting and to analyse associated clinical factors and costs. We evaluated consecutive patients admitted to an EMU at a tertiary care hospital over a 10-year period based on a descriptive, longitudinal study. We analysed the occurrence of AEs (traumatic injury, psychiatric complications, status epilepticus, cardiorespiratory disturbances, and death), investigated potential risk factors using univariate and multivariate logistic regression analysis, and compared admission costs between patients with and without AEs. In total, 411 EMU admissions were studied corresponding to 352 patients (55% women; mean [SD] age: 41.7 [12.1] years). Twenty-five patients (6%) experienced an AE. The most common event was traumatic injury (n=9), followed by status epilepticus (n=8), psychiatric complications (n=7), and cardiorespiratory disturbances (n=1). On comparing patients with and without AEs, we observed that the former were more likely to experience generalized seizures (OR: 7.81; 95% CI: 3.51-12.23; p<0.001) or have more seizures overall during admission (OR: 3.2; 95% CI: 1.42-6.8; p=0.002). Patients with AEs also had longer EMU stays (6.91 [2.64] vs 5.08 [1.1]; p=0.004), longer hospital stays (8.45 [3.6] vs 5.18 [1.2]; p<0.001), and higher costs (€7277.71 [€2743.9] vs €5175.7 [€1182.5]; p<0.001). Patients with generalized seizures and more seizures during admission were at greater risk of AEs, which were associated with higher admission costs.

Correlation of blood biomarkers with early-onset seizures after an acute stroke event.

INTRODUCTION: Blood biomarkers have not been widely studied in stroke-related seizures. In this study, we aimed to describe clinical factors and biomarkers present during acute stroke and to analyze their association with early-onset seizures. METHODS: We retrospectively evaluated a panel of 14 blood biomarkers in 1115 patients with ischemic and hemorrhagic stroke. Biomarkers were normalized and standardized using Z scores. We also recorded stroke and epilepsy-related variables, including stroke severity (National Institute of Health Stroke Scale [NIHSS] scores), type, and causes, time from onset of stroke to occurrence of early seizures, and type of seizure. Adjusted logistic regression models were built to identify clinical variables and biomarkers independently associated with early seizures. RESULTS: Mean ±â€¯standard deviation (SD) age was 72.3 ±â€¯13.2 years, and 56.8% of the patients were men. Thirty-eight patients (3.9%) developed early seizures with a median time to onset of 1 day (interquartile range (IQR), 0-4). A higher NIHSS score (odds ratio [OR] = 1.046; 95% confidence interval (CI): 1.001-1.094; p = 0.044) and hemorrhagic stroke (OR = 2.133; 95% CI: 1.010-4.504; p = 0.047) were independently associated with a greater risk of early seizures. Independent blood biomarkers predictive of early seizures were lower levels of tumor necrosis factor receptor 1 (TNF-R1) (<0.013) (p = 0.006; OR = 3.334; 95% CI: 1.414-7.864) and higher levels of neural cell adhesion molecule (NCAM) (>0.326) (p = 0.009; OR = 2.625; 95% CI: 1.271-5.420). The predictive power of the regression model was greater when clinical variables were combined with blood biomarkers (73.5%; 95% CI: 65.1%-81.9%) than when used alone (64%; 95% CI: 55%-72.9%). CONCLUSION: Higher NCAM and lower TNF-R1 levels may help predict the occurrence of early seizures. The combined use of these biomarkers and clinical variables could be useful for identifying patients at risk of seizures. This article is part of the Special Issue "Seizures & Stroke".

Refractory status epilepticus: Impact of baseline comorbidity and usefulness of STESS and EMSE scoring systems in predicting mortality and functional outcome.

PURPOSE: Little has been published on the prognostic value of the Status Epilepticus Severity Score (STESS) or the Epidemiology-based Mortality score in Status Epilepticus (EMSE) in refractory status epilepticus (RSE). We sought to analyze the prognostic value of STESS and EMSE and the impact of baseline comorbidities in mortality and functional outcome in RSE. METHODS: We designed an observational retrospective study of patients diagnosed with RSE between August 2013 and September 2017. For each patient, we analyzed prospectively recorded demographic, clinical, comorbidity, electroencephalographic, treatment, and hospital stay-related data and calculated STESS and EMSE. All variables were compared statistically between patients with good and poor functional outcome at discharge and between patients who died in hospital and those who were alive at discharge. RESULTS: Fourty-nine patients had RSE; 35.4% died in hospital and 88% showed functional decline at discharge. Mortality was associated with baseline chronic kidney disease (CKD) (OR 19.25, p = 0.006), baseline modified Rankin scale score (mRS) (OR 3.38, p = 0.005), non-convulsive status epilepticus (NCSE) with coma (OR 11.9, p = 0.04), STESS (OR 2, p = 0.04), and EMSE (OR 1.3, p = 0.02). Functional outcome was associated with baseline mRS (OR 13.9, p = 0.02), and EMSE (OR 1.3, p = 0.02). The optimal cutoff scores for predicting mortality were 4 for STESS and 60 for EMSE. EMSE predicted functional outcome with an optimal cutoff of 40. CONCLUSIONS: CKD, NCSE with coma and STESS were associated with mortality. mRS and EMSE were associated with mortality and functional outcome. EMSE was useful for predicting functional outcome, while EMSE and STESS were useful for predicting in-hospital mortality.

Neurological manifestations of excessive alcohol consumption. / Manifestaciones neurológicas del alcoholismo.

This article reviews the different acute and chronic neurological manifestations of excessive alcohol consumption that affect the central or peripheral nervous system. Several mechanisms can be implicated depending on the disorder, ranging from nutritional factors, alcohol-related toxicity, metabolic changes and immune-mediated mechanisms. Recognition and early treatment of these manifestations is essential given their association with high morbidity and significantly increased mortality.

Diagnostic Yield of Routine Electroencephalography With Concurrent Video Recording in Detecting Interictal Epileptiform Discharges in Relation to Reasons for Request: A Prospective Study of 1,080 Video-Electroencephalograms.

PURPOSE: The aim of this study was to prospectively analyze the sensitivity and specificity of routine electroencephalography with concurrent video recording (vEEG) in relation to the reasons for requesting the test and to investigate when routine vEEG should be requested. METHODS: We prospectively analyzed 1,080 consecutive vEEGs performed between April 2015 and April 2016. The requests for vEEG were classified as requests with a low suspicion of epilepsy (syncope, confusion or delirium, suspicion of psychogenic nonepileptic seizures, and paroxysmal focal neurological deficit) or requests with a high suspicion of epilepsy (first clinical seizure, suspected status epilepticus, follow-up study of a patient with epilepsy, and acute symptomatic seizures). Predominant vEEG findings (ictal and interictal epileptiform activities, diffuse, or focal slowing and triphasic waves) were analyzed, and sensitivity and specificity [ZERO WIDTH SPACE][ZERO WIDTH SPACE]values calculated. RESULTS: The most common indication for vEEG was a follow-up study of patients with epilepsy (38%), followed by first clinical seizure (19.3%) and suspected status epilepticus (11%). The respective specificity and sensitivity values were 93% and 58% for 235 vEEGs performed in children/adolescents (≤18 years), 95% and 40% for 533 vEEGs performed in adults (>18 ≤ 65 years), and 93% and 39% for 312 vEEGs performed in older adults (>65 years). Twenty-four patients with false-positive paroxysms had a clinical diagnosis of confusional state or paroxysmal focal neurological deficit. Neurologists and neuropediatricians with experience in managing epilepsy had higher specificity values than general neurologists or physicians (P = 0.012). CONCLUSIONS: In our series, vEEG abnormalities were mainly observed in patients with clinical findings highly suggestive of epilepsy. In confusional states, and paroxysmal focal neurological deficit vEEG could be indicated.

Importance of neuropsychological and clinical features to predict seizure control in medically treated patients with mesial temporal epilepsy and hippocampal sclerosis.

OBJECTIVE: It is not yet understood why seizures in certain patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) develop resistance to antiepileptic drugs (AEDs) while others achieve good seizure control with this treatment. We analyzed clinical and neuropsychological features associated with seizure control in patients with MTLE-HS who had not undergone resective surgery. METHODS: We enrolled 40 patients with medically treated MTLE-HS and retrospectively collected the following data from prospective databases: sex, febrile seizures, central nervous system infection, history of head trauma, cognitive impairment, psychiatric disturbances, history of status epilepticus, age at onset of epilepsy, aura, seizure type and frequency, electroencephalography abnormalities, HS side, AEDs, global cognitive status, and neuropsychological functions such as cognitive processing speed, attention and executive functions, verbal and visual memory, language, and visuospatial ability. These factors were compared between patients who achieved seizure control (no seizures or a >50% reduction in seizure frequency) with AED treatment and those who continued with poor seizure control (increase or no change in frequency or <50% reduction) after starting treatment. RESULTS: The factors associated with poor seizure control in the multivariate analysis were >2seizures per month before treatment (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.2-4.8, p=0.04), moderate or severe cognitive impairment (OR 2.1, 95% CI 1.8-7.6, p=0.02), and impairment of >2 neuropsychological functions (OR 2.88, 95% CI 2-6.6, p=0.04). No associations were observed between poor seizure control and specific neuropsychological function impairment. CONCLUSIONS: Poor seizure control in MTLE-HS is associated with moderate-severe cognitive impairment but not with a specific profile of impairment. Recognizing poor prognostic features such as a high frequency of monthly seizures prior to starting AED treatment could help to identify patients with medically intractable MTLE-HS who may be good candidates for early epilepsy surgery.

Risk factors for temporary work disability.

INTRODUCTION: The relationship among labor difficulties and psychiatric disorders is important and bidirectional. However, current information about the influence of psychiatric disorders in temporary work disability in Spain is inconclusive. For this reason, we aimed to describe the prevalence of the conclusions of psychiatric expert’s reports including maintain o revoke the temporary disability (TD). We also aimed to compare sociodemographic, clinical and therapeutic variables according with the decision of maintain or revoke this condition. METHODOLOGY: A descriptive study was conducted in psychiatric patients that were examined by psychiatric experts during one year. At the examination time, the patients had a sick leave mean of 5 months. The psychiatric experts assessed their ability to work according to the interference of the psychiatric symptoms. RESULTS: A total of 380 patients were included (66.8% women, 42±10.9 years), 87.9% had a result of revoke the temporary work disability. No sociodemographic or therapeutic factors were associated with the continuity of sick leave. The most common diagnosis of patients who obtained a revoked temporary work disability was adjustment disorder (66.2% vs 13%, p=0.001) and patients who maintained the temporary work disability was major depressive disorder (45.7% vs 3.9%, p=0.001). CONCLUSIONS: After a psychiatric expert’s examination the most of the results suggest to revoke the temporary work disability. Major depressive disorder is the most commonly diagnostic associated to continue sick leave.

Administrative prevalence of insomnia and associated clinical features in patients with addiction during active substance use.

INTRODUCTION: A bidirectional relation between substance use and insomnia has been described, although there are few studies examining insomnia in the population of people with addiction. The aim of this study was to describe the prevalence of insomnia during active substance use in patients with addiction and its associated clinical features. PATIENTS AND METHODS: Descriptive study in patients diagnosed with substance dependence disorder admitted to a Hospital Detoxification Unit. The existence of insomnia prior to admission was assessed using the Oviedo Sleep Questionnaire (OSQ). Demographic variables, consumptionrelated clinical variables, and diagnostic variables were collected and the SCID-I and -II (Structured Clinical Interview for DSM-IV) and CAADID (Conners’ Adult ADHD Diagnostic Interview for DSM-IV) were administered to evaluate the psychiatric diagnoses. Bivariate and multivariate analyses were made of the data. RESULTS: 481 patients (72.6% men, age 40.6±10.1 years) were enrolled. 64.3% of the patients reported insomnia during active substance use. The most common type of insomnia was fragmented nocturnal sleep (49.9%). The factors significantly associated with insomnia were polysubstance drug use, medical comorbidities (most notably, infectious diseases), anxiety disorder, personality disorder (particularly cluster C), a greater number of previous admissions for detoxication, and early age at onset of substance use. CONCLUSIONS: Insomnia is highly prevalent in patients with addiction during active use of the substance. Fragmented nocturnal sleep was the most common type of insomnia. Patients with addiction and comorbid anxiety disorder, medical comorbidity, and early onset of dependence were more likely to experience insomnia.

Baseline Differences in Minor Lymphocyte Subpopulations may Predict Response to Fingolimod in Relapsing-Remitting Multiple Sclerosis Patients.

AIMS: Fingolimod, oral treatment for relapsing-remitting multiple sclerosis (RRMS), is an agonist of sphingosine and its metabolite S1P that binds their receptors, blocking the egress of lymphocytes from lymph nodes. The aim of this study was immunomonitoring of minor peripheral lymphocyte subpopulations in RRMS patients under treatment with fingolimod and correlation with treatment response. METHODS: Prospective study. T- and B-cell subpopulations were analyzed using multiparametric flow cytometry in peripheral blood from 14 RRMS patients under treatment with fingolimod at baseline, +1, +3, +6, +9, and +12 months of follow-up. Response to therapy was assessed at month +12. RESULTS: Most changes in minor lymphocyte subpopulations occurred in the first month of treatment and were maintained until the end of follow-up. The basal percentages of recent thymic emigrants (RTEs) and transitional B cells were lower in responder patients than in nonresponders. After 1 month of follow-up, the percentages of late effector memory CD4(+) T cells in peripheral blood were higher in responder patients. CONCLUSION: If confirmed in a bigger cohort of patients, analysis of percentages of minor lymphocyte subpopulations in peripheral blood of patients with RRMS prior and after +1 month of treatment might predict clinical response to fingolimod.

Multiparametric flow cytometric analysis of whole blood reveals changes in minor lymphocyte subpopulations of multiple sclerosis patients.

OBJECTIVE: The objective of this study is to characterise the functionally relevant minor lymphocyte subpopulations in whole blood of multiple sclerosis (MS) patients and their potential utility as biomarkers for treatment follow up. MATERIAL AND METHODS: Peripheral blood from 40 healthy donors (HD) and 66 MS patients [23 relapsing-remitting (RRMS) without treatment, 27 RRMS undergoing treatment (16 IFN-ß, 11 natalizumab), and 16 progressive forms (eight secondary progressive and eight primary progressive)] was analysed by multiparametric flow cytometry. RESULTS: Untreated MS patients showed a decrease in early effector memory (CD45RA(-)CCR7(-)CD27(+)) CD4(+) and CD8(+) T cells and an increase in Th17 lymphocytes in peripheral blood compared with HD. Regarding the effect of treatment, whereas no differences in relative percentages of cellular subpopulations were observed in patients under IFN-ß treatment, those under treatment with natalizumab had an increased percentage of early effector memory CD4(+) (CD45RA(-)CCR7(-)CD27(+)), central memory CD8(+) (CD45RA(-)CCR7(+)CD27(+)) T cells, recent thymic emigrants (CD4(+) CD45RA(+)CCR7(+)CD27(+)CD31(+)PTK7(+)) and transitional B cells (CD19(+)CD27(-)CD24(hi)CD38(hi)). CONCLUSIONS: Multiparametric flow cytometry analysis of whole blood is a robust, reproducible, and sensitive technology to monitor the effect of MS treatments even in minor lymphocyte subpopulations that might represent useful biomarkers of treatment response.

Baseline clinical status as a predictor of methylprednisolone response in multiple sclerosis relapses.

BACKGROUND: To date, there are no available factors to predict the outcome after multiple sclerosis relapse. AIM: To investigate factors that may be useful for predicting response to methylprednisolone treatment, following a relapse of multiple sclerosis (MS). METHODS: The study included 48 MS patients enrolled in a double-blind multicenter trial to receive intravenous versus oral high-dose methylprednisolone treatment. Associations were sought between the disability status prior to relapse and the relapse severity, determined by changes in the Expanded Disability Status Scale (EDSS) score, as well as the improvements after treatment. We also analyzed the relationships between the number of magnetic resonance imaging (MRI) gadolinium-enhancing lesions (Gd+) and improvement. RESULTS: A higher EDSS score before relapse was associated with more severe relapses (p = 0.04) and less marked improvement (odds ratio (OR) 1.8; 95% CI (1.2-2.2); p = 0.05) after methylprednisolone treatment. Relapse severity (p = 0.29) and the number of Gd+ lesions at relapse (p = 0.41) were not related with improvement. CONCLUSIONS: Clinical baseline status prior to MS relapse is a predictor of response to methylprednisolone treatment.

Beneficial effect of tolerogenic dendritic cells pulsed with MOG autoantigen in experimental autoimmune encephalomyelitis.

BACKGROUND: Treatment with tolerogenic dendritic cells (TolDC) is a promising, cell-based strategy to regulate autoimmune diseases such as multiple sclerosis (MS) in an antigen-specific way. This technique involves the use of TolDC from MS patients cultured in the presence of vitamin D(3) (VitD3) and pulsed with myelin peptides to induce a stable hyporesponsiveness in myelin-specific autologous T cells. AIM: The purpose of this study was to analyze the in vivo effect of VitD3-TolDC treatment on experimental autoimmune encephalomyelitis, an animal model of MS. METHODS: Bone marrow-derived TolDC cultured in the presence of VitD3 and pulsed with peptide 40-55 of the myelin oligodendrocyte glycoprotein (MOG(40-55)) were administrated preventively, preclinically, and therapeutically to EAE-induced mice. RESULTS: We found that VitD3-TolDC-MOG treatment showed a beneficial effect, not only decreasing the incidence of the disease but also reducing the severity of the clinical signs mediated by induction of regulatory T cells (Treg), as well as IL-10 production and reduction of Ag-specific lymphoproliferation. Our results support VitD3-TolDC-peptide(s) treatment as a potential strategy to restore tolerance in autoimmune diseases such as MS.