Emerging biomarkers for improving pregnancy planning in multiple sclerosis.

Background: Patient disability, relapse rate, and age are used for family planning in multiple sclerosis (MS). However, the need for more accurate biomarkers is widely recognized. We aimed to explore the influence of age on neurofilament light chain (sNfL), which reflects acute inflammation; glial fibrillary acidic protein (GFAP), associated with disability progression independent of relapses; and anti-Müllerian hormone (AMH), reflecting ovarian reserve, to provide a tailored family planning strategy. Methods: This case-control study included 95 MS patients and 61 healthy control women (HCW). sNfL and GFAP levels were measured using a sensitive single-molecule array assay. AMH levels were measured by the automated Elecsys® Anti-Müllerian Hormone Assay. Results: We observed no significant differences in AMH values between MS patients and the control group within any of the age-matched categories. Age exhibited a negative correlation with AMH values in both groups, as expected. Nevertheless, our findings suggest a slight tendency toward reduced ovarian reserve in MS patients (rho MS patients = -0.67, p < 0.0001; rho HCW = -0.43, p = 0.0006). Interestingly, among the 76 MS participants under 40 years old, we identified ten individuals (13.1%) with AMH levels below 0.7 ng/ml, indicative of a low ovarian reserve, and an additional six individuals (7.8%) with AMH levels between 0.7 ng/ml and 0.9 ng/ml, suggesting a potential risk of premature ovarian failure. Conversely, sNfL and GFAP levels in the MS group exhibited high variability but showed no significant association with age intervals. Conclusion: We found no significant differences in AMH, sNfL or GFAP values between MS patients and the control group within any of the age-matched categories. The assessment of AMH, sNFL and GFAP levels at MS onset facilitates personalized therapeutic and family planning strategies for childbearing-age women.

Spasticity-Plus syndrome in multiple sclerosis patients in a tertiary hospital in Spain.

Introduction: Spasticity is a common symptom in multiple sclerosis (MS) and it is often associated with other symptoms such as spasms/cramps and pain. The concept of Spasticity-Plus syndrome takes into account that spasticity is accompanied by one or more symptoms (spasms/cramps, pain, bladder dysfunction, sleep disorders, fatigue and/or tremor). As these symptoms share a common cannabinoid control, therapy acting on cannabinoid receptors may be useful. The main study objectives were to determine the number of MS patients who met Spasticity-Plus syndrome criteria and to identify the most common symptoms. Methods: Clinical records of MS patients treated with nabiximols in a tertiary hospital from 2002 to 2022 were reviewed retrospectively. Results: Of the 73 patients included in the study, 53.4% were women, and most had secondary progressive MS (64.4%). All patients met the criteria for Spasticity-Plus syndrome: 100% had spasticity and at least another symptom. Pain was the second most common symptom (91.8%), followed by spasms/cramps (79.4%), and fatigue (76.7%). Sleep disturbances (p < 0.0001) and tremor (p < 0.027) were more frequent in patients with relapsing-remitting MS than in patients with progressive MS. No statistically significant differences were found for spasticity, pain, spasms/cramps, and fatigue between MS phenotypes. Regarding symptoms clusters, 94.4% of the patients had three or more symptoms. Spasticity was more frequently associated with pain (91.8%) and spasms/cramps (79.4%). Conclusion: Spasticity-Plus syndrome was present in all the study population of patients with different MS phenotypes, and treated with nabiximols.

Real-World Retrospective Analysis of Alemtuzumab Outcomes in Relapsing-Remitting Multiple Sclerosis: The LEMCAM Study.

BACKGROUND: Alemtuzumab is a high-efficacy treatment approved for relapsing-remitting multiple sclerosis (RRMS). Although clinical trials and observational studies are consistent in showing its efficacy and manageable safety profile, further studies under clinical practice conditions are needed to further support its clinical use. OBJECTIVE: The aim of this observational retrospective study was to evaluate the effectiveness and safety of alemtuzumab to add to the current real-world evidence on the drug. METHODS: A cohort of 115 adult patients with RRMS treated with alemtuzumab between 2014 and 2020 was retrospectively followed up in five centers in Spain. Analysis included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW), 6-month confirmed disability improvement (CDI), radiological activity, no evidence of disease activity (NEDA-3), and safety signals. Given the different follow-up periods among participants, ARR was calculated using the person-years method. CDI was defined as a ≥ 1.0-point decrease in Expanded Disability Status Scale (EDSS) score assessed in patients with a baseline EDSS score ≥ 2.0 confirmed 6 months apart. CDW was defined as a ≥ 1.0-point increase in EDSS score assessed in patients with a baseline EDSS score ≥ 1.0 (≥ 1.5 if baseline EDSS = 0), confirmed 6 months apart. RESULTS: ARR decreased from 1.9 (95% confidence interval 1.60-2.33) in the year prior to alemtuzumab initiation to 0.28 (0.17-0.37) after 1 year of treatment (87% reduction), and to 0.22 (0.13-0.35) after the second year. Over the entire follow-up period, ARR was 0.24 (0.18-0.30). At year 1, 75% of patients showed no signs of magnetic resonance imaging (MRI) activity and 70% at year 5. One percent of patients experienced 6-month CDW at year 1, 2.6% at year 2, 7.4% at year 3, and no patients over years 4 and 5. A total of 7.7% of patients achieved 6-month CDI in year 1, 3.6% in year 2, and maintained it at years 3 and 4. Most patients achieved annual NEDA-3: year 1, 72%; year 2, 79%; year 3, 80%; year 4, 89%; year 5, 75%. Infusion-related reactions were observed in 95% of patients and infections in 74%. Thyroid disorders occurred in 30% of patients, and only three patients developed immune thrombocytopenia. No cases of progressive multifocal leukoencephalopathy were reported. CONCLUSIONS: This study shows that alemtuzumab reduced the relapse rate and disability worsening in real-world clinical practice, with many patients achieving and sustaining NEDA-3 over time. The safety profile of alemtuzumab was consistent with previous findings, and no new or unexpected safety signals were observed. As this was an observational and retrospective study, the main limitation of not having all variables comprehensively available for all patients should be considered when interpreting results.

Changes in the Expression of TGF-Beta Regulatory Pathway Genes Induced by Vitamin D in Patients with Relapsing-Remitting Multiple Sclerosis.

Vitamin D is an environmental factor related to multiple sclerosis that plays a significant role in immune regulation. TGF-ß is a superfamily of cytokines with an important dual effect on the immune system. TGF-ß inhibits the Th1 response while facilitating the preservation of regulatory T cells (FOXP3+) in an immunoregulatory capacity. However, when IL-6 is present, it stimulates the Th17 response. Our aim was to analyze the regulatory effect of vitamin D on the in vivo TGF-ß signaling pathway in patients with relapsing-remitting multiple sclerosis (RRMS). A total of 21 patients with vitamin D levels < 30 ng/mL were recruited and supplemented with oral vitamin D. All patients were receiving disease-modifying therapy, with the majority being on natalizumab. Expression of SMAD7, ERK1, ZMIZ1, BMP2, BMPRII, BMP4, and BMP5 was measured in CD4+ lymphocytes isolated from peripheral blood at baseline and one and six months after supplementation. SMAD7 was overexpressed at six months with respect to baseline and month one. ERK1 was overexpressed at six months with respect to month one of treatment. No significant differences in expression were observed for the remaining genes. No direct correlation was found with serum vitamin D levels. BMPRII expression changed differentially in non-natalizumab- versus natalizumab-treated patients. Changes were observed in the expression of ERK1, BMP2, and BMP5 based on disease activity measured using the Rio-Score, BMP2 in patients who had relapses, and BMP5 in those whose EDSS worsened. Our results suggest indirect regulation of vitamin D in TGF-ß pathway genes in patients with RRMS.

Mental health among displaced and non-displaced populations in Valledupar, Colombia: do inequalities continue?

During the long-lasting civil war in Colombia, thousands of people were displaced mainly from rural to urban areas, causing social disruption and prolonged poverty. This study aimed at analyzing the traumatic experience many years ago on the current psycho-emotional status of displaced families as well as the ongoing inequalities regarding displaced and non-displaced communities in one of the most affected areas by the armed conflict. An interview survey was conducted among 211 displaced families and 181 non-displaced families in 2 adjacent compounds in Valledupar, Colombia. The questionnaire used questions from the validated national survey and was revised and applied by staff members of the departmental secretary of health who conducted additional in-depth interviews. The study showed that the living conditions of the displaced community were precarious. The past traumatic events many years ago and the current difficult living conditions are associated with psychological problems being more frequent among the displaced people. The displaced people had experienced more violent acts and subsequently had a larger number of emotional symptoms (fright, headache, nervousness, depression, and sleeplessness). Other stress factors like economic problems, severe disease or death of family members and unemployment prevailed among displaced persons. The non-displaced lived in a more protected environment with less exposure to violence and stress, although belonging to a similarly low socio-economic stratum. It is recommended to take measures for a better protection of the displaced community, improve their access to the job market, offer different leisure activities and facilitate public transport.

Short-chain fatty acids during pregnancy in multiple sclerosis: A prospective cohort study.

BACKGROUND AND PURPOSE: Short-chain fatty acids (SCFAs) can have pro- or anti-inflammatory properties, but their relationship with multiple sclerosis (MS) relapses during pregnancy remains unknown. This study aimed to explore SCFA profiles in MS patients during pregnancy and to assess their association with the appearance of relapses during pregnancy and postpartum. METHODS: We prospectively included 53 pregnant MS patients and 21 healthy control women. Patients were evaluated during pregnancy and puerperium. SCFAs were measured by liquid chromatography-mass spectrometry. RESULTS: Sixteen patients (32%) had relapses during pregnancy or puerperium, and 37 (68%) did not. All MS patients showed significant increases in acetate levels during pregnancy and the postpartum period compared to non-MS women. However, propionate and butyrate values were associated with disease activity. Their values were higher in nonrelapsing patients and remained similar to the control group in relapsing patients. The variable that best identified active patients was the propionate/acetate ratio. Ratios of <0.36 during the first trimester were associated with higher inflammatory activity (odds ratio = 165, 95% confidence interval = 10.2-239.4, p < 0.01). Most nonrelapsing patients showed values of >0.36, which were similar to those in healthy pregnant women. CONCLUSIONS: Low propionate/acetate ratio values during the first trimester of gestation identified MS patients at risk of relapses during pregnancy and the postpartum period.

Risk and outcomes of COVID-19 in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Limited information is available on incidence and outcomes of COVID-19 in patients with multiple sclerosis (MS). This study investigated the risks of SARS-CoV-2 infection and COVID-19-related outcomes in patients with MS, and compared these with the general population. METHODS: A regional registry was created to collect data on incidence, hospitalization rates, intensive care unit admission, and death in patients with MS and COVID-19. National government outcomes and seroprevalence data were used for comparison. The study was conducted at 14 specialist MS treatment centers in Madrid, Spain, between February and May 2020. RESULTS: Two-hundred nineteen patients were included in the registry, 51 of whom were hospitalized with COVID-19. The mean age ± standard deviation was 45.3 ± 12.4 years, and the mean duration of MS was 11.9 ± 8.9 years. The infection incidence rate was lower in patients with MS than the general population (adjusted incidence rate ratio = 0.78, 95% confidence interval [CI] = 0.70-0.80), but hospitalization rates were higher (relative risk = 5.03, 95% CI = 3.76-6.62). Disease severity was generally low, with only one admission to an intensive care unit and five deaths. Males with MS had higher incidence rates and risk of hospitalization than females. No association was found between the use of any disease-modifying treatment and hospitalization risk. CONCLUSIONS: Patients with MS do not appear to have greater risks of SARS-CoV-2 infection or severe COVID-19 outcomes compared with the general population. The decision to start or continue disease-modifying treatment should be based on a careful risk-benefit assessment.

Evolution of antibody titres against Epstein-Barr virus and human herpesvirus 6A/B and expression of multiple sclerosis-associated retrovirus in the serum of pregnant multiple sclerosis patients.

Epstein-Barr virus (EBV), human herpesvirus 6A/B (HHV-6A/B) and multiple sclerosis (MS)-associated retrovirus (MSRV) have been described as possible MS triggers. We analysed antibody titres against EBV and HHV-6, and MSRV envelope (env) mRNA expression, in the serum of pregnant multiple sclerosis patients (P-MS) to study their possible link to the clinical activity of MS during pregnancy and postpartum and their possible role as relapse predictors. For that purpose, serum samples were collected from 71 pregnant women (50 pregnant MS and 21 pregnant healthy controls-P-HC) during pregnancy and postpartum. Relating to antibody titres, IgM antibody titres against HHV-6A/B were significantly higher in P-MS than in P-HC both in each pregnancy trimester and in the postpartum period. Moreover, IgM antibody titres against HHV-6A/B were higher in P-MS who suffered a relapse during the postpartum. Regarding MSRV env mRNA expression, the prevalence in the first trimester of pregnancy was significantly higher in P-MS who suffered relapses during pregnancy. Summing it up, high IgM antibody titres against HHV-6A/B and MSRV env mRNA expression during the first trimester of pregnancy could act as relapse predictors for the gestation/postpartum periods.

Cytokine profile during pregnancy predicts relapses during pregnancy and postpartum in multiple sclerosis.

OBJECTIVE: To explore the serum cytokine profile associated with disease activity during pregnancy and postpartum in MS, and to assess any potential biomarkers predicting the occurrence of relapses during this period. METHODS: We included 53 MS pregnant women recruited between 2007 and 2018. Interferon-gamma, Tumor necrosis factor-alpha, interleukin-17, granulocyte/macrophage-colony stimulating factor, Activin-A, interleukin-10, and programmed-death-ligand-1 (PD-L1) were measured quarterly in serum by ELISA. RESULTS: Seventeen patients (32%) experienced relapses during pregnancy or puerperium and 37(68%) did not. We did not found differences in clinical characteristics or treatment status between the two groups. However, relapsing patients showed at the first trimester of pregnancy considerably lower levels of serum Activin-A (336.4 pg/dl [289.6-491.7], median [IQR] vs. 760.0 pg/dl [493.2-1108.0],p = .003), which correlated positively with serum PD-L1 (r = 0.53,p = .0005) and IL-10 (r = 0.43,p = .004) values. Activin-A levels lower than 515 pg/ml at the first trimester identified patients with high probability of relapsing during pregnancy and postpartum (OR = 13.75, CI: 2.5-76.8, p = .001). CONCLUSIONS: MS patients with no relapses during pregnancy and puerperium showed an early triggering of a tolerogenic innate immune response evidenced by high serum Activin-A concentrations during the first trimester of pregnancy. Thus, serum Activin-A can be a useful biomarker to predict clinical activity during this period.

Plasma exchange in acute attacks of demyelinating diseases of the central nervous system: clinical outcomes and predictors of response.

BACKGROUND: Plasma exchange (PLEX) is a therapeutic option in the treatment of acute attacks of Demyelinating Diseases of the Central Nervous System (DDCNS). Factors related with PLEX response are not well established. METHODS: Descriptive and retrospective study. We included patients treated with PLEX for acute attacks of DDCNS between 2008 and 2017. We recorded demographics, clinical and treatment-related data, and Expanded Disability Status Scale (EDSS) score at admission, at discharge, and at 6 months. RESULTS: We included 64 patients. Forty-eight (75%) were female with a mean age of 48.28 ± 11.5 years. Half of our patients were diagnosed with multiple sclerosis. Clinical improvement was achieved in 51.6% at discharge and 62.5% at 6 months. The logistic regression model showed that EDSS score > 3 at admission (p = 0.04) and early clinical improvement with PLEX (p = 0.00) were predictors of good response to PLEX at discharge and at 6 months, respectively. No serious adverse effects were identified. CONCLUSIONS: PLEX is a safe and effective treatment for acute attacks of DDCNS. EDSS score at admission and early clinical improvement with PLEX were factors associated with good response to PLEX.

Exposición a fármacos modificadores de la enfermedad durante el embarazo en esclerosis múltiple: estudio prospectivo / Pregnancy exposure to disease-modifying drugs in multiple sclerosis: a prospective study

INTRODUCCIÓN: En esclerosis múltiple (EM), la exposición fetal a fármacos modificadores de la enfermedad (FME) conlleva distintos grados de riesgo. OBJETIVO: analizar nuestra experiencia en relación con los casos de exposición fetal involuntaria a FME. PACIENTES Y MÉTODOS: Estudio observacional. Se analizaron los datos clínico-obstétricos de una cohorte de pacientes con EM, entre 2007 y 2017. Grupo EM: pacientes con EM con embarazos expuestos a FME. Grupo control: pacientes con EM no expuestas y embarazadas sanas. RESULTADOS: Hubo un total de 68 embarazos en pacientes con EM. Control: 56 mujeres sanas. Grupo EM expuestas a FME durante embarazo: 13; bajo peso al nacer: 2(15%); parto pretérmino: 0. Grupo EM no expuestas a FME: 55; 22 (40%) suspendieron FME previo embarazo; 33 (60%) naïve; bajo peso al nacer: 5 (9%); pretérmino: 7 (12%). Grupo mujeres sanas: bajo peso al nacer, 6 (11%); parto pretérmino, 6 (11%). No hubo diferencias clínicas estadísticamente significativas entre pacientes EM. Tampoco hubo diferencias en peso al nacer, tiempo de gestación o morbilidad obstétrica en expuestas a FME. CONCLUSIONES: No hubo diferencias clínicas estadísticamente significativas, ni mayor morbilidad obstétrica, entre pacientes expuestas a FME, no expuestas y embarazadas sanas

INTRODUCTION: In multiple sclerosis (MS), foetal exposure to disease-modifying drugs (DMDs) carries varying degrees of risk. We sought to analyse the clinical and obstetric outcomes of MS patients (MSp) exposed to DMDs during pregnancy. PATIENTS AND METHODS: Observational study. We analysed the clinical-obstetric data of a cohort MSp, who became pregnant between 2007-2017. They were prospectively followed up during pregnancy and postpartum. CONTROL GROUP: healthy pregnant women (HPW) and MSp unexposed to DMDs. RESULTS: Sixty-eight pregnancies in MSp. Fifty-six HPW. Thirteen MSp were exposed to DMDs during pregnancy. Obstetric outcome: 2 (15%) infants had low birth weight, no preterm deliveries. Fifty-five MSp were not exposed to DMDs: 22 (40%) discontinued DMD before pregnancy, 33(60%) naïve. Five infants (9%) had low birth weight and 7 (12%) were preterm. HPW: 56. Low birth weight 6 (11%), preterm delivery 6 (11%). There were no differences in relapse incidence during pregnancy-puerperium between MSp groups. There were no differences in birth weight, gestation time, delivery-caesarean section. We found no special obstetric morbidity in women exposed to DMDs. CONCLUSIONS: There were no significant differences in the clinical and obstetric variables analysed between pregnant women exposed to DMDs, unexposed, and HPW

Pregnancy exposure to disease-modifying drugs in multiple sclerosis: a prospective study. / Exposición a fármacos modificadores de la enfermedad durante el embarazo en esclerosis múltiple: estudio prospectivo.

INTRODUCTION: In multiple sclerosis (MS), foetal exposure to disease-modifying drugs (DMDs) carries varying degrees of risk. We sought to analyse the clinical and obstetric outcomes of MS patients (MSp) exposed to DMDs during pregnancy. PATIENTS AND METHODS: Observational study. We analysed the clinical-obstetric data of a cohort MSp, who became pregnant between 2007-2017. They were prospectively followed up during pregnancy and postpartum. CONTROL GROUP: healthy pregnant women (HPW) and MSp unexposed to DMDs. RESULTS: Sixty-eight pregnancies in MSp. Fifty-six HPW. Thirteen MSp were exposed to DMDs during pregnancy. Obstetric outcome: 2 (15%) infants had low birth weight, no preterm deliveries. Fifty-five MSp were not exposed to DMDs: 22 (40%) discontinued DMD before pregnancy, 33(60%) naïve. Five infants (9%) had low birth weight and 7 (12%) were preterm. HPW: 56. Low birth weight 6 (11%), preterm delivery 6 (11%). There were no differences in relapse incidence during pregnancy-puerperium between MSp groups. There were no differences in birth weight, gestation time, delivery-caesarean section. We found no special obstetric morbidity in women exposed to DMDs. CONCLUSIONS: There were no significant differences in the clinical and obstetric variables analysed between pregnant women exposed to DMDs, unexposed, and HPW.

Absceso epidural espinal por Streptococcus agalactiae en un paciente inmunocompetente / Spinal epidural abscess caused by Streptococcus agalactiae in an immunocompetent patient

Introducción: Streptococcus agalactiae es un microorganismo causal infrecuente en el absceso epidural espinal (AEE) que generalmente afecta a pacientes con comorbilidades predisponentes y/o alguna potencial fuente de infección. Caso clínico: Presentamos el caso de un paciente de 53años, inmunocompetente y sin antecedentes médicos de interés, que desarrolló un cuadro de dolor lumbar, paraparesia y disfunción de esfínteres en el contexto de un síndrome febril sin foco conocido de una semana de evolución. La exploración neurológica mostró paraparesia flácida proximal, nivel sensitivo T10, esfínter anal atónico y reflejos osteotendinosos normales. La RM medular mostró un extenso AEE dorsal. Se realizó una laminectomía urgente con drenaje del absceso en menos de 24h y se inició antibioterapia empírica. El resultado del cultivo mostró Streptococcus agalactiae. Tras un estudio exhaustivo, no se encontró ninguna enfermedad predisponente ni fuente de la infección. Conclusiones: Describimos un caso infrecuente de AEE causado por Streptococcus agalactiae en un paciente sano sin factores predisponentes. Este caso subraya la importancia del diagnóstico precoz de esta entidad, dado que se puede asociar potencialmente con un mejor pronóstico

Background: Streptococcus agalactiae is an uncommon microorganism that causes spinal epidural abscess (SEA) and usually affects individuals with a predisposing condition or potential source of infection. Case description: We present the case of an immunocompetent 53-year-old patient with an unremarkable past medical history who developed progressive low extremity weakness, bowel and bladder dysfunction and genital sensory impairment. A neurological exam on admission revealed flaccid proximal paraparesis, T10 sensory level, atonic anal sphincter and normal myotatic reflexes. Urgent neuroimaging showed a large thoracic epidural spinal abscess. Laminectomy and abscess drainage were immediately performed and systemic antibiotic treatment was initiated. Abscess cultures revealed Streptococcus agalactiae. After an exhaustive workup no predisposing factors or local or systemic source for the infection were found. Conclusions: We report a singular case of spinal epidural abscess caused by Streptococcus agalactiae in a healthy patient with no predisposing factors. This case also highlights the importance of an early diagnosis and treatment to obtain a better neurological outcome

Spinal epidural abscess caused by Streptococcus agalactiae in an immunocompetent patient. / Absceso epidural espinal por Streptococcus agalactiae en un paciente inmunocompetente.

BACKGROUND: Streptococcus agalactiae is an uncommon microorganism that causes spinal epidural abscess (SEA) and usually affects individuals with a predisposing condition or potential source of infection. CASE DESCRIPTION: We present the case of an immunocompetent 53-year-old patient with an unremarkable past medical history who developed progressive low extremity weakness, bowel and bladder dysfunction and genital sensory impairment. A neurological exam on admission revealed flaccid proximal paraparesis, T10 sensory level, atonic anal sphincter and normal myotatic reflexes. Urgent neuroimaging showed a large thoracic epidural spinal abscess. Laminectomy and abscess drainage were immediately performed and systemic antibiotic treatment was initiated. Abscess cultures revealed Streptococcus agalactiae. After an exhaustive workup no predisposing factors or local or systemic source for the infection were found. CONCLUSIONS: We report a singular case of spinal epidural abscess caused by Streptococcus agalactiae in a healthy patient with no predisposing factors. This case also highlights the importance of an early diagnosis and treatment to obtain a better neurological outcome.

Multi-centre validation of a flow cytometry method to identify optimal responders to interferon-beta in multiple sclerosis.

BACKGROUND AND OBJECTIVES: Percentages of blood CD19+CD5+ B cells and CD8+perforin+ T lymphocytes can predict response to Interferon (IFN)-beta treatment in relapsing-remitting multiple sclerosis (RRMS) patients. We aimed to standardize their detection in a multicenter study, prior to their implementation in clinical practice. METHODS: Fourteen hospitals participated in the study. A reference centre was established for comparison studies. Peripheral blood cells of 105 untreated RRMS patients were studied. Every sample was analyzed in duplicate in the participating centre and in the reference one by flow cytometry. When needed, participating centres corrected fluorescence compensations and negative cut-off position following reference centre suggestions. Concordance between results obtained by participating centres and by reference one was evaluated by intraclass correlation coefficients (ICC) and Spearman correlation test. Centre performance was measured by using z-scores values. RESULTS: After results review and corrective actions implementation, overall ICC was 0.86 (CI: 0.81-0.91) for CD19+CD5+ B cell and 0.89 (CI: 0.85-0.93) for CD8+ perforin+ T cell quantification; Spearman r was 0.92 (0.89-0.95; p <0.0001) and 0.92 (0.88-0.95; p <0.0001) respectively. All centres obtained z-scores≤0.5 for both biomarkers. CONCLUSION: Homogenous percentages of CD19+CD5+ B cells and CD8 perforin+ T lymphocytes can be obtained if suitable compensation values and negative cut-off are pre-established.

A Case of Toxic Epidermal Necrolysis Secondary to Acetaminophen in a Child.

OBJECTIVE: To report and discuss a serious cutaneous adverse reaction in a child who was treated with acetaminophen (paracetamol). CASE SUMMARY: A five years old male child presented a pruriginous maculopapular rash and a "drug-induced Stevens-Johnson syndrome/Toxic Epidermal Necrolysis" was suspected. Applying Spanish Pharmacovigilance System probability algorithm (modified Karch-Lasagna algorithm) for the suspected drugs (acetaminophen, ibuprofen and azithromycin), the causality of this adverse reaction was possible for acetaminophen and unlikely for the other two drugs. In this case it was recommended suspending and avoiding treatment with acetaminophen. This adverse reaction was reported to the Spanish Pharmacovigilance System (notification number: 10-600428). DISCUSSION: Skin adverse reactions induced by drugs are uncommon but often serious and potentially fatal. There are few cases reports of "Stevens-Johnson syndrome/Toxic Epidermal Necrolysis" associated with acetaminophen in the literature. We present a documented case in a child. According to modified Karch-Lasagna algorithm, this case represents a possible adverse reaction. CONCLUSION: Hypersensitivity reactions with skin involvement are rarely associated with acetaminophen ingestion, but in a population such as the paediatric population, in which its use is widespread, the involvement of this drug should always be suspected if no other possible cause at sight.

Vascular imaging before intravenous thrombolysis: consequences of in-hospital delay in applying two diagnostic procedures.

BACKGROUND: Vascular imaging is increasingly used for diagnosis of arterial occlusions in acute ischemic stroke (AIS) patients. Our aim was to determine whether computed tomography angiography (CTA) and Doppler/duplex ultrasound (DUS) before intravenous thrombolysis (IVT) is associated with a delay in time-to-treatment. METHODS: Observational analysis of a prospective cohort of AIS patients treated with IVT from January 2009 to December 2012. Patients were classified into three groups: the noncontrast computed tomography (NCCT) group (patients studied only with NCCT before IVT), CTA group (patients who underwent CTA in addition to NCCT), and the DUS group (patients studied with NCCT+DUS). RESULTS: We treated 244 patients: 116 patients (47.5%) were studied with NCCT, 79 (32.4%) with CTA, and 49 (20.1%) with DUS. Door-to-needle time was significantly higher in the CTA group (median 60 [48-77] minutes) than in the NCCT group (51.5 [40-65]) and DUS group (48 [42-61]) (P = .008). No differences were observed for onset-to-door time and onset-to-needle time. In the multivariate linear regression analysis, onset-to-door time, prehospital stroke code activation, and performance of CTA influenced door-to-needle time. CONCLUSIONS: Performing CTA before IVT seems to increase door-to-needle time. Vascular imaging based on DUS should be considered only if this does not lead to in-hospital delay.

Acute cervical myelopathy due to presumed fibrocartilaginous embolism: a case report and systematic review of the literature.

INTRODUCTION: Fibrocartilaginous embolism (FCE) is an uncommon cause of myelopathy that should be considered after more common causes have been ruled out. OBJECTIVE: This article presents a case report of a 50-year-old man with acute myelopathy attributed to FCE and summarizes the clinical features of the disease by analyzing all of the published evidence. DATA SOURCES AND EXTRACTION: Two computerized literature searches (MEDLINE-Pubmed, EMBASE, the Cochrane Library) were performed. The search term used was "Fibrocartilaginous embolism." No language restrictions were applied. All articles were evaluated and key data were extracted according to predefined criteria: patient's age, year of publication, localization of the embolism and type of vascular syndrome, clinical outcome, and time to death in the fatal cases. RESULTS: Fifty-two cases (39 biopsy proven and 13 clinically diagnosed) were found in the literature. Median age at presentation was 37 years (interquartile range, 19-53) and 56% were women. Median progression of symptoms was 6 hours (interquartile range, 5-60 h), predominantly affecting the cervical spine (48%) by an arterial embolic source (56%). CONCLUSIONS: FCE is an unusual cause of spinal cord and cerebral ischemia with unknown incidence. Implementation of diagnostic imaging techniques and initial management of acute spinal disorders care in intensive care units might increase the incidence of disease antemortem. FCE should be considered in the differential diagnosis of ischemic spinal cord injury when no other causes can be identified and especially when the onset is progressive over several hours.

From Zinnia to Arabidopsis: approaching the involvement of peroxidases in lignification.

Zinnia elegans constitutes one of the most useful model systems for studying xylem differentiation, which simultaneously involves secondary cell wall synthesis, cell wall lignification, and programmed cell death. Likewise, the in vitro culture system of Z. elegans has been the best characterized as the differentiation of mesophyll cells into tracheary elements allows study of the biochemistry and physiology of xylogenesis free from the complexity that heterogeneous plant tissues impose. Moreover, Z. elegans has emerged as an excellent plant model to study the involvement of peroxidases in cell wall lignification. This is due to the simplicity and duality of the lignification pattern shown by the stems and hypocotyls, and to the basic nature of the peroxidase isoenzyme. This protein is expressed not only in hypocotyls and stems but also in mesophyll cells transdifferentiating into tracheary elements. Therefore, not only does this peroxidase fulfil all the catalytic requirements to be involved in lignification overcoming all restrictions imposed by the polymerization step, but also its expression is inherent in lignification. In fact, its basic nature is not exceptional since basic peroxidases are differentially expressed during lignification in other model systems, showing unusual and unique biochemical properties such as oxidation of syringyl moieties. This review focuses on the experiments which led to a better understanding of the lignification process in Zinnia, starting with the basic knowledge about the lignin pattern in this plant, how lignification takes place, and how a sole basic peroxidase with unusual catalytic properties is involved and regulated by hormones, H2O2, and nitric oxide.

Longitudinally extensive varicella-zoster virus myelitis in a patient with multiple sclerosis.

STUDY DESIGN: Case report. OBJECTIVE: To report this rare varicella-zoster virus (VZV) complication in a patient with multiple sclerosis. SUMMARY OF BACKGROUND DATA: Longitudinally extensive transverse myelitis is a spinal cord lesion that extends over 3 or more vertebral segments. A common feature in neuromyelitis optica, longitudinally extensive transverse myelitis can also occur in several other diseases. METHODS: A 15-year-old boy with relapsing-remitting multiple sclerosis, who has been treated with immunomodulators for 6 months, developed a subacute left brachiocrural hemiparesis with ipsilateral decreased sensation in the trunk and limbs. This was interpreted as a new relapse and was treated consequently. During the evolution, the patient developed a cutaneous rash in the left C8 metameres, followed by asymmetric tetraparesis. RESULTS: Magnetic resonance imaging demonstrated an extensive cervical-thoracic myelopathy. Cerebrospinal fluid analysis revealed 17 leukocytes per microliter (95% mononuclear), protein 41 mg/dL, and negative VZV-DNA by polymerase chain reaction, but elevated anti-VZV immunoglobulin G cerebrospinal fluid/serum index, with a normal albumin cerebrospinal fluid/serum index, all of which were consistent with intrathecal synthesis of anti-VZV antibody. We were able to rule out all other causes included in the differential diagnosis, namely, vascular disease, tumor, and autoimmune conditions, especially those associated with neuromyelitis optica spectrum disorders. CONCLUSION: Awareness of the potentially varied presentation of VZV myelitis can enable earlier recognition and specific treatment.