Gadolinium-enhanced brain lesions in multiple sclerosis relapse.

OBJECTIVE: To study the clinico-radiological paradox in multiple sclerosis (MS) relapse by analyzing the number and location of gadolinium-enhanced (Gd+) lesions on brain MRI before methylprednisolone (MP) treatment. METHODS: We analyzed brain MRI from 90 relapsed MS patients in two Phase IV multicenter double-blind randomized clinical trials that showed the noninferiority of different routes and doses of MP administration. A 1.5- or 3-T brain MRI was performed at baseline before MP treatment and within 15 days of symptom onset. The number and location of Gd+ lesions were analyzed. Associations were studied using univariate analysis. RESULTS: Sixty-two percent of patients had at least 1 Gd+ brain lesion; the median number was 1 (interquartile range 0-4), and 41% of patients had 2 or more lesions. The most frequent location of Gd+ lesions was subcortical (41.4%). Gd+ brain lesions were found in 71.4% of patients with brainstem-cerebellum symptoms, 57.1% with spinal cord symptoms and 55.5% with optic neuritis (ON). Thirty percent of patients with brain symptoms did not have Gd+ lesions, and only 43.6% of patients had symptomatic Gd+ lesions. The univariate analysis showed a negative correlation between age and the number of Gd+ lesions (p=0.002). CONCLUSION: Most patients with relapse showed several Gd+ lesions on brain MRI, even when the clinical manifestation was outside of the brain. Our findings illustrate the clinico-radiological paradox in MS relapse and support the value of brain MRI in this scenario.

Recommendations for vaccination in patients with multiple sclerosis who are eligible for immunosuppressive therapies: Spanish consensus statement. / Recomendaciones para la vacunación en pacientes con esclerosis múltiple candidatos a terapias inmunosupresoras: documento de consenso español.

BACKGROUND: The recent development of highly effective treatments for multiple sclerosis (MS) and the potential risk of infectious complications require the development of prevention and risk minimisation strategies. Vaccination is an essential element of the management of these patients. This consensus statement includes a series of recommendations and practical scenarios for the vaccination of adult patients with MS who are eligible for highly effective immunosuppressive treatments. METHODOLOGY: A formal consensus procedure was followed. Having defined the scope of the statement, we conducted a literature search on recommendations for the vaccination of patients with MS and specific vaccination guidelines for immunosuppressed patients receiving biological therapy for other conditions. The modified nominal group technique methodology was used to formulate the recommendations. DEVELOPMENT: Vaccination in patients who are candidates for immunosuppressive therapy should be considered before starting immunosuppressive treatment providing the patient's clinical situation allows. Vaccines included in the routine adult vaccination schedule, as well as some specific ones, are recommended depending on the pre-existing immunity status. If immunosuppressive treatment is already established, live attenuated vaccines are contraindicated. For vaccines with a correlate of protection, it is recommended to monitor the serological response in an optimal interval of 1-2 months from the last dose.

Onset-adjusted incidence of multiple sclerosis in the Girona province (Spain): Evidence of increasing risk in the south of Europe.

BACKGROUND: Recent studies show an increasing incidence of multiple sclerosis (MS) in southern Europe. Although by its geographical location and genetic characteristics Spain is expected to be similar to other southern European regions, data on incidence are scarce. The aim of this study was to determine the onset-adjusted incidence of MS in the Girona province in Catalonia (Spain). METHODS: A prospective incidence study pooling data from the population-based Catalonia MS Registry was performed. Incident cases were defined as patients who had the onset of symptoms compatible with a clinically isolated syndrome (CIS) suggestive of MS in 2009 and fulfilled McDonald-2005 criteria during follow-up. Age- and sex-specific incidence rates were obtained. RESULTS: The Registry included 182 patients residing in Girona that presented a CIS from January 2009 to December 2013. Fifty one patients had the onset of symptoms in 2009, of whom 27 patients fulfilled the diagnostic criteria, giving an incidence of 3.6 per 100,000 (CI 95% 2.4-5.3) inhabitants; 4.3 (CI 95% 2.5-7.1) for women and 2.9 (CI 95% 1.4-5.2) for men. The age-adjusted incidence rate for the European population was 3.29 (CI 95% 3.2-3.3). CONCLUSION: The incidence estimation derived in this study is consistent with recent epidemiological data of MS in southern Europe suggesting an increase in incidence in this region.

Similar biological effect of high-dose oral versus intravenous methylprednisolone in multiple sclerosis relapses.

UNLABELLED: Our aim was to investigate differences in immune mechanisms in multiple sclerosis (MS) relapse, after high-dose oral methylprednisolone (oMP) or intravenous methylprednisolone (ivMP). We measured serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and IFN-γ) in 39 of 49 MS patients with moderate-severe relapse, whom were treated with ivMP or oMP in a placebo-controlled, non-inferiority clinical trial. We assessed these cytokine levels at baseline and at 1 and 4 weeks post-treatment. The cytokine levels between oMP and ivMP were similar at any time. Proinflammatory cytokines (IL-6 and IFN-γ) were significantly decreased in both groups at week 1 (p = 0.05 / p = 0.03) and at week 4 (p = 0.04 / p = 0.05). This study provides further confirmatory evidence that oMP is not inferior to ivMP. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00753792.

A randomized clinical trial of oral versus intravenous methylprednisolone for relapse of MS.

BACKGROUND: Steroids improve multiple sclerosis (MS) relapses but therapeutic window and dose, frequency and administration route remain uncertain. OBJECTIVE: The objective of this paper is to compare the clinical and radiologic efficacy, tolerability and safety of intravenous methylprednisolone (ivMP) vs oral methylprednisolone (oMP), at equivalent high doses, for MS relapse. METHODS: Forty-nine patients with moderate or severe relapse within the previous 15 days were randomized in a double-blind, noninferiority, multicenter trial to receive ivMP or oMP and their matching placebos. Expanded Disability Status Scale (EDSS) scores were determined at baseline and weeks 1, 4 and 12. Brain MRI were assessed at baseline and at weeks 1 and 4. Primary endpoint was a noninferiority assessment of EDSS improvement at four weeks (noninferiority margin of one point), with further key efficacy assessments of number and volume of T1 gadolinium-enhancing (Gd+), and new or enlarged T2 lesions at four weeks' post-treatment initiation. Secondary outcomes were safety and tolerability. RESULTS: The study achieved the main outcome of noninferiority at four weeks for improved EDSS score. No differences were found between ivMP and oMP in the number of Gd+ lesions (0 (0-1) vs 0 (0-0.5), p = 0.630), volume of Gd+ lesions (0 (0-88.0) vs 0 (0-32.9) mm(3), p = 0.735), or new or enlarged T2 lesions (0 (0-194) vs 0 (0-123), p = 0.769). MP was well tolerated, and no serious adverse events were reported. CONCLUSIONS: This study provides confirmatory evidence that oMP is not inferior to ivMP in reducing EDSS, similar in MRI lesions at four weeks for MS relapses and is equally well tolerated and safe. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00753792.

[Hybrid-NOTES transvaginal hemi-nephrectomy for duplicated renal collecting system in the adult patient]. / Heminefrectomía NOTES-híbrido transvaginal por duplicidad del sistema colector renal en el paciente adulto.

INTRODUCTION: Duplication of the ureter and renal pelvis is the most common anomaly of the upper urinary tract. Upper pole heminephrectomy is a treatment option when duplication anomalies are associated with ureteral ectopia or ureterocele with an associated nonfunctioning or infected upper pole moiety. MATERIAL AND METHOD: We describe a NOTES hybrid transvaginal upper pole heminephrectomy in a 24 year old with recurrent infections in a poorly functioning right upper pole moiety. The procedure was performed with a bariatric trocar in the vagina, and a multichannel single-port device (Triport, Olympus Surgical) in the umbilicus. An ultrasonic scalpel was used for the heminephrectomy. The specimen was retrieved through the vagina. RESULTS: Operative time was 150 minutes and blood loss 50 cc. One week later the patient developed urinoma at the surgical site and was re-explored laparoscopically. The cut edge of the heminephrectomy defect was fulgurated and a drain placed. The patient recovered uneventfully following re-exploration. CONCLUSIONS: We describe the technique for transvaginal Hybrid-NOTES heminephrectomy. This approach requires further development with respect to instrumentation, and surgical expertise. The combined umbilical and vaginal approached restored triangulation and facilitates dissection, but more experience is required to determine safety, efficacy and reproducibility.

[A novel technique for distal ureterectomy and bladder cuff excision]. / Nueva técnica para la ureterectomía distal y excisión de manguito vesical.

INTRODUCTION: We describe a novel endoscopic approach and provide a literature review for the "en bloc" dissection of the distal ureter and bladder cuff during laparoscopic radical nephroureterectomy using a transvesical single port approach under pneumovesicum. MATERIALS AND METHODS: The procedure was performed in an 80-year old male with a history of gross hematuria due to left renal pelvic TCC and no history of prior bladder TCC. Laparoscopic radical nephroureterectomy was performed and the ureter was dissected down to the bladder and clipped. A single-port device was inserted transvesically and pneumovesicum established. A full thickness incision of the bladder around the ureter was performed with progressive intravesical mobilization of the distal ureter. Subsequently, a water-tight closure of the bladder defect was achieved. The distal ureter, together with the bladder cuff, was then delivered en bloc laparoscopically with the specimen. RESULTS: The operating time (LESS radical nephroureterectomy, RPLND, and bladder cuff excision) was 6hours and 15minutes. The bladder cuff time was 45minutes. There were no intra or postoperative complications and the catheter was removed after 6 days. Histopathological analysis showed kidney-invasive papillary urothelial cancer, pT3 pN0 (0/7) G3. CONCLUSION: The distal ureter and bladder cuff techniques have not yet been standardized. Management of the bladder cuff with a single port is feasible. Additional studies are needed to identify the best approach for management of the distal ureter at the time of laparoscopic nephroureterectomy.

Multiple sclerosis and cognitive decline: is ApoE-4 a surrogate marker?

BACKGROUND - The role of the apolipoprotein E (ApoE) polymorphism has been well demonstrated in neurodegenerative disorders such as Alzheimer. However, its role in multiple sclerosis (MS) remains unclear. AIMS - The aims of our study were as follows: (i) to assess whether ApoE-4 might be a surrogate marker of cognitive decline in MS; (ii) to confirm the presence of cognitive impairment in mildly disabled patients treated with interferon-beta; and (iii) to analyse the correlation between cognitive disturbances and clinical variables. MATERIAL AND METHODS - Fifty relapsing-remitting MS patients underwent a battery of neuropsychological tests and were genotyped for ApoE. Their scores were compared with those of 35 controls. RESULTS - No association was found between ApoE-4 and cognitive impairment. Significant differences in most domains were observed between MS and the control group. Cognitive decline was not related to disability progression. CONCLUSION - No association between cognitive impairment and ApoE-4 or clinical markers was detected in our MS patients.

Anticipation of age at onset in multiple sclerosis: methodologic pitfalls.

BACKGROUND/AIM: There are several reports that claim anticipation in complex or polygenic diseases such as multiple sclerosis (MS), Crohn disease or schizophrenia. The aim of the present study was to assess age at onset of MS during the last 60 years in the region of Costa de Ponent (Barcelona, Spain) showing how apparent changes in age at onset between generations can be an artefact of analysis based on cohorts that have not been followed enough time. METHODS: The study comprised 1100 patients diagnosed of MS. The method used to correct for follow-up time bias involves constructing comparison cohorts that had been observed for the same amount of time. To ensure equal follow-up times, we restricted our analysis to patients whose onset was by 37 years of age (percentile 75) and were at least 37 years old. We analysed differences in age at onset using log-rank test to compare survival curves estimated by Kaplan-Meier method. RESULTS: Age at onset decreases progressively from older to younger generations. However, when adjustment to equal follow-up time was done, anticipation in age at onset was not found. CONCLUSION: Anticipation of age at onset is undetectable when adjusted for follow-up time.

[Multiple sclerosis epidemiological situation update: pertinence and set-up of a population based registry of new cases in Catalonia]. / Situación epidemiológica actual de la esclerosis múltiple: pertinencia y puesta en marcha de un registro poblacional de nuevos casos en Cataluña.

INTRODUCTION: The first epidemiological studies on multiple sclerosis (MS) around the world pictured a north to south latitudinal gradient that led to the first genetic and environmental pathogenic hypothesis. MS incidence seems to be increasing during the past 20 years based on recent data from prospective studies performed in Europe, America and Asia. This phenomenon could be explained by a better case ascertainment as well as a change in causal factors. The few prospective studies in our area together with the increase in the disease in other regions, justifies an epidemiological MS project in order to describe the incidence and temporal trends of MS. DEVELOPMENT: A prospective multicenter MS registry has been established according to the actual requirements of an epidemiological surveillance system. Case definition is based on the fulfillment of the McDonald diagnostic criteria. The registry setting is the geographical area of Cataluna (northeastern Spain), using a wide network of hospitals specialized in MS management. CONCLUSION: Recent epidemiological studies have described an increase in MS incidence. In order to contrast this finding in our area, we consider appropriate to set up a population based registry.

Status epilepticus with visual seizures in ketotic hyperglycemia.

Metabolic disturbances are often associated with epileptic seizures, but the pathogenesis of this relationship is poorly understood. We describe the case of a 48-year-old man who presented with complex partial status epilepticus with visual seizures in the context of ketotic hyperglycemia. The EEG revealed a temporal epileptogenic focus and alterations were apparent on MRI in the acute phase and 4 months later. Very few cases of seizures in ketotic patients have been reported because ketone bodies have a protective effect against epilepsy. Seizures in hyperglycemia tend to be partial, and the only reports of visual seizures were due to occipital foci. Neuroradiological alterations have been reported in epileptic seizures, although usually in generalized seizures. The clinical, electrical, and imaging characteristics of this case are interesting and suggest that partial seizures can also cause long-term neuronal damage.

An approach to estimating the intangible costs of multiple sclerosis according to disability in Catalonia, Spain.

Multiple sclerosis (MS) is a chronic demyelinating disease, which represents a great economic burden to society. Cost-of-illness studies of MS tend to underestimate the intangible costs related to pain, anxiety and helplessness. The purpose of this study was to estimate the intangible costs of MS, and determine whether these costs increase as disability progresses. We studied 211 consecutive patients with MS who attended our MS unit. Patients mean age was 41.6 (SD: 10.7) years, 69% were female, and their mean Expanded Disability Status Scale (EDSS) score was 2.47 (SD: 2.05). Quality-of-life was measured with the EuroQoL visual analogue scale. Quality-adjusted life year (QALY) was calculated for each patient. Patients were grouped into five disability stages according to their EDSS, and QALY was compared between patients and a group of healthy controls matched by age and sex. A benchmark value was ascribed to each QALY lost, and the intangible costs per patient-year were calculated as Euros 0 (EDSS =0), Euros 1100 (EDSS =1-3), Euros 8250 (EDSS =3.5-5.5), Euros 9900 (EDSS =6-7) and Euros 11,000 (EDSS >7.5). Sensitivity analysis showed a similar progression of costs. We conclude that intangible costs are relevant in MS, especially when disability increases. Although the method to calculate the costs remains controversial, we consider that they should be included in cost analysis of MS.

Specificity of frontal dysfunctions in relapsing-remitting multiple sclerosis.

Various studies have reported deficits in frontal cognitive functions in patients with multiple sclerosis (MS). However, the frontal deficit is not uniform and is often very subtle. The aim of this study was to assess frontal functions in a broad sample of patients with relapsing-remitting multiple sclerosis at the mild-to-moderate stage. The sample included a series of 165 patients. We used a test battery covering the frontal functions that have been described as being altered in MS. Significant differences were found between the patient group and healthy controls on the WAIS Arithmetic subtest, the PASAT, category word recall and the number of trials required to reach the first category of the WCST. In conclusion, we observed significant differences with respect to the control group in terms of information processing speed and working memory. These functions involve connections between the frontal lobe and other brain regions.

[The costs of a multiple sclerosis relapse in Catalonia (Spain)]. / ¿Cuánto cuesta un brote de esclerosis múltiple en Cataluña?

INTRODUCTION: The objective of this study is to calculate direct, indirect and intangible costs of a relapse in multiple sclerosis (MS) in our cohort of patients. METHODS: Data from patient questionnaires, hospital charts, Catalan Public Healthcare System tariffs and Catalan Statistics Institute. We employed a cost-of-illness method. The human capital approach was used to estimate indirect costs, and quality-of-life measurements were used to estimate intangible costs. RESULTS: 148 MS patients monitored in our MS-Unit consecutively answered the questionnaire elaborated. We calculated 1,498.5-1,537.9 euros for direct costs (hospital admission and outpatient, respectively) and 1,530.6 euros for indirect costs. We estimated an average total cost of 3,048.8 euros per patient/relapse. We also calculated intangible costs, 539 euros per patient and relapse, which should be added to the previous figure. CONCLUSIONS: The total cost of a MS relapse in our population (3,048.8 euros) is lower than the cost reported in the literature. The economic impact of MS is due to its disabling progression rather than to relapses

Regression to the mean in multiple sclerosis.

In order to ensure sufficient disease activity, patients with relapsing remitting (RR) multiple sclerosis (MS) are often included in randomized placebo-controlled trials, only if they have a high baseline activity. These patients, whose evolution is unusual in the pre-study period, will tend to show a more usual behavior when followed up over a period of time. This phenomenon is known as regression to the mean. Regression to the mean should be taken into account in correctly interpreting long-term studies of cohorts treated without a placebo control group, which use the baseline period as control. The aim of this study was to evaluate the relevance of this phenomenon in a non-treated cohort of RRMS patients, selected with similar criteria to those used in randomized placebo-controlled clinical trials. Forty-four patients with definite RRMS, with two or more relapses in the previous two years, and a baseline EDSS < or = 5.5 were prospectively followed. The mean number of relapses spontaneously decreased from 1.72 (SD: 1.4) in the year prior to enrolment, to 1.0 (SD: 1.3) during the first year of follow-up (P < 0.05). Regression to the mean may explain as much as 40% of the reduction in the relapse rate from the baseline period to the period on-study.

Resistencia de staphylococcus aureus a los antimicrobianos en Venezuela 1988-1998 / Resistance of staphylococcus to the anti-microbial in Venezuela 1988-1908

S.aureuses un patógeno importante en el medio hospitalario y en la comunidad. Analizamos su comportamiento frente a los antimicrobianos según su uso clínico y estructura farmacológica. Estudiamos 30.344 cepas de Staphylococcus aureous procedentes de los centros de salud del Grupo Venezolano de Vigilancia de la Resistencia Bacteriana a los Antimicrobianos (GVRB) realizando antibiogramas según las normas del NCCLS, y utilizando el análisis de series cronológicas, con los siguientes resultados. Antibióticos de primera línea: oxacilina, disminuyó; la variación porcentual fue del 64 por ciento, con respecto al primer valor de la serie Vancomicina disminuyó el 100 por ciento. El descenso de la resistencia o oxacilina y vancomicina pareciera depender de las mejoras introducidas en las técnicas de determinación de la resistencia a estos antibióticos. ß-lactámicos: ampicilina-sulbactam aumentó un 66,7 por ciento; aminoglucósidos: amikacina disminuyó 50 por ciento y gentamicina 63,20 por ciento. Quinolonas: ciprofloxacina aumentó un 300 por ciento y norfloxacina 50 por ciento. Otros: todos presentaron descenso. El uso de vancomicina debe reservarse para infecciones severas por cepas de S.aureus con comprobada resistencia a oxacilina

Infección nosocomial II: resistencia a ß-lactámicos y aminoglucósidos en pseudomonas aeruginosa en centros médicos de Venezuela durante el año 2000 / Nosocomial infection II: resistance to ß-lactams and aminoglycosides in pseudomonas aeruginosa at the Venezuelan medical centres 2000

Entre el 5 y el 10 por ciento de los pacientes que ingresan a hospitales de EE UU adquieren una o más infecciones dentro del hospital. Una cuarta parte de esas infecciones nosocomiales están representadas por infecciones de la Unidad de Cuidados Intensivos (UCI). De estas últimas, el 70 por ciento son producidas por microorganismos resistentes a antimicrobianos; constituyendo este último, un problema de salud global por sí solo. El alto grado de resistencia por parte de estos microorganismos es una de las razonas más relevantes que contribuyen a incrementar el número de muertes en los casos de infección nosocomial. Los bacilos Gram-negativos son los primeros responsables de infección nosocomial, y entre ellos P. aeruginosa es la primera en frecuencia. La división entre diferentes ecosistemas en el hospital refleja diferentes poblaciones con diferentes características. En este estudio presentamos comparaciones de los porcentajes de resistencia ante ß-lactámicos y aminoglicósidos en P. aeuruginosa nosocomial (UCI y cirugía) y comunitaria (COM), en centros médicos de Venezuela, diferenciando los públicos (Hpu) de los privados (Hpri), para el año 2000. Se usó el método de difusión de disco, de acuerdo al NCCLS [National committe for Clinical Laboratories Standars (Comite Nacional de Estándares para Laboratorios Clínicos)]. Se siguió el programa software WHONET (World Health Organization Net). Se incluyeron todas las cepas reportadas en los diferentes servicios. Se realizó la evaluación estadística por prueba Z (p< 0,05). Se muestran diferencias significativas en la frecuencia de resistencia (fr) en P. aeruginosa nosocomial entre UCI/COM en Hpu (mayores diferencias: piperacilina, 44,8 por ciento y gentamicina, 39/10 por ciento, entre UCI/CI (la mayor = piperac, 44/23 por ciento y la menor cefepime, 10/8 por ciento. 2. Hay diferencias significativas entre la frb de CI de Hpu/Hpri, siendo las mayores =: piper, 23/15 por ciento piper-tazob, 11/2 por ciento; tobra, 25/2 por ciento, netilm, 25/8 por ciento; genta, 37/22 por ciento. No se observaron diferencias significativas entre UCI de Hpu/Hpri. 3. No hubo diferencias en la frb ante Amg para Paeruginosa entre UCI/Ci de Hpu, pero sí de Hpri (mayores =: tobra,40/1 y netilm, 40/9). 4. Tiene relevancia las diferencias observadas ante ß-L entre UCI/CI y entre éstos y la comunidad, tanto en Hpu como Hpri.

Cambios en la resistencia de Staphylococcus aureus a los antimicrobianos en centros clínicos del área Metropolitana de Caracas Venezuela: período 1995-2002 / Changes in the resistance of staphylococcus aureus to antimicrobials in clinical centers of Metropolitan area of Caracas Venezuela: period 1995-2002

El objetivo de este trabajo fue estudiar los cambios en la resistencia a los antimicrobianos de aislados de Staphylococcus aureus (SA) provemientes de muestras clínicas recuperadas en tres centros de salud del área Metropolitana de Caracas durante el período 1995-2002. Los datos se obtuvieron de los Servicios de Bacteriología del Hospital Vargas (HV), Hospital Clínico Universitario (HCU) y Centro Médico (CM), participantes del Grupo Venezolano de Vigilancia de la Resistencia Bacteriana a los antimicrobianos (GVRB). Analizamos 6.291 cepas de S. aureus mediante pruebas de sensibilidad a los antimicrobianos por el método de difusión en agar. Los rangos de resistencia registrados fueron HV: oxacilina (Ox) 9 a 33 por ciento, vancomicina (Van) 0 a 1 por ciento, gentamicina (Gen) 2 a 16 por ciento, ciprofloxacina (Cip) 1 a 13 por ciento, eritromicina (E) 10 a 25 por ciento y trimetoprim-sulfametoxazol (SXT) 2 a 13 por ciento. HUC: Ox 3 a 18 por ciento, Van 0 a 2 por ciento, Gen 5 a 33 por ciento cip 3 a 14 por ciento, E 10 a 30 por ciento y SXT 1 a 10 por ciento. CM: ox4 a 20 por ciento, Van 0 por ciento, Gen 5 a 10, Cip 2 a 14 por ciento, E 16 a 29 por ciento y SXT 1 a 6 por ciento. Los porcentajes de resistencia de este patógeno en estos centros en general, reflejan una tendencia al aumento, especialmente citprofloxacina, eritromicina y trimetoprim-sulfame toxazol. Sin embargo, los valores reportados para oxacilina son inferiores a los hallados en países asiáticos, Europa, EE UU y otros países de América Latina