Cultural adaptation and validation of a peninsular Spanish version of the MSTCQ© (Multiple Sclerosis Treatment Concerns Questionnaire). / Adaptación cultural y validación al español de España del MSTCQ© (Multiple Sclerosis Treatment Concerns Questionnaire).

INTRODUCTION: Although subcutaneous treatments for multiple sclerosis (MS) have been shown to be effective, adverse reactions and pain may adversely affect treatment satisfaction and adherence. This study presents an adapted and validated Spanish version of the Multiple Sclerosis Treatment Concerns Questionnaire© (MSTCQ), which evaluates satisfaction with the injection device (ID) across 4 domains: injection system (A), side effects (B) (flu-like symptoms, reactions, and satisfaction), experience with treatment (C) and benefits (D). METHODS: Two study phases: 1) Cultural adaptation process with input from experts (n=6) and patients (n=30). 2) Validation obtained by means of an observational, cross-sectional, multi-centre study evaluating 143 adult MS patients using an ID. Tools employed: MSTCQ©, Patient-Reported Indices for Multiple Sclerosis (PRIMUS©), and Treatment Satisfaction Questionnaire for Medication (TSQM©). Psychometric properties: Feasibility (percentage of valid cases and floor/ceiling effects); Reliability (Cronbach α) and test-retest correlation (n=41, intraclass correlation coefficient, ICC); and construct validity (factor analysis of domains A and B) and convergent validity (Spearman rank-order correlation for MSTCQ© vs TSQM©). RESULTS: Mean age (SD) was 41.94 (10.47) years, 63% of the group were women, and 88.11% presented relapsing-remitting MS. Mean (SD) EDSS score was 2.68 (1.82) points. MSTCQ© completion was high (0%-2.80% missing data). Internal consistency was high at α=0.89 for the total score (A+B) and α=0.76, 0.89, and 0.92 for domains A, B, and C, respectively. The version demonstrated excellent test-retest reliability for the total (ICC=0.98) and for domains A, B, and C: ICC=0.82, 0.97, and 0.89, respectively. Factor analysis corroborated the internal structure of the original questionnaire. The association between total and domain scores on both the MSTCQ© and the TSQM© was moderately strong (Rho=0.42-0.74) and significant (P<.05 and P<.01). CONCLUSION: The Spanish version of MSTCQ© demonstrates appropriate psychometric properties.

Messenger RNA encoding constitutively active Toll-like receptor 4 enhances effector functions of human T cells.

Adoptive T cell therapy of cancer employs a large number of ex-vivo-propagated T cells which recognize their targets either by virtue of their endogenous T cell receptor (TCR) or via genetic reprogramming. However, both cell-extrinsic and intrinsic mechanisms often diminish the in-vivo potency of these therapeutic T cells, limiting their clinical efficacy and broader use. Direct activation of human T cells by Toll-like receptor (TLR) ligands induces T cell survival and proliferation, boosts the production of proinflammatory cytokines and augments resistance to regulatory T cell (Treg) suppression. Removal of the TLR ligand-binding region results in constitutive signalling triggered by the remaining cytosolic Toll/interleukin-1 receptor (TIR) domain. The use of such TIR domains therefore offers an ideal means for equipping anti-tumour T cells with the arsenal of functional attributes required for improving current clinical protocols. Here we show that constitutively active (ca)TLR-4 can be expressed efficiently in human T cells using mRNA electroporation. The mere expression of caTLR-4 mRNA in polyclonal CD8 and CD4 T cells induced the production of interferon (IFN)-γ, triggered the surface expression of CD25, CD69 and 4-1BB and up-regulated a panel of cytokines and chemokines. In tumour-infiltrating lymphocytes prepared from melanoma patients, caTLR-4 induced robust IFN-γ secretion in all samples tested. Furthermore, caTLR-4 enhanced the anti-melanoma cytolytic activity of tumour-infiltrating lymphocytes and augmented the secretion of IFN-γ, tumour necrosis factor (TNF)-α and granulocyte-macrophage colony-stimulating factor (GM-CSF) for at least 4 days post-transfection. Our results demonstrate that caTLR-4 is capable of exerting multiple T cell-enhancing effects and can potentially be used as a genetic adjuvant in adoptive cell therapy.

Alemtuzumab treatment in real clinical practice: Experience in a multicenter cohort.

BACKGROUND: Alemtuzumab is a highly effective treatment for relapsing remitting multiple sclerosis (RRMS), but in recent years safety-related concerns had emerged due to description of novel serious side effects not registered in CARE-MS I and CARE-MS II phase 3 studies, nor in TOPAZ extension study. Data about alemtuzumab use in real clinical practice are limited and based mainly on retrospective studies with small sample sizes. Therefore, more information about effectiveness and safety of alemtuzumab in this context is needed. METHODS: A multicenter observational prospective study to investigate effectivity and safety of alemtuzumab in a real-world setting was performed. Primary endpoints were the change in annualized relapse rate (ARR), and in disability measured by EDSS score. Secondary endpoints were the cumulative probability of confirmed 6-month disability improvement and worsening. Disability worsening and disability improvement were considered when the EDSS score was increased or decreased, respectively, in 1 point if baseline EDSS score was <5.0, or in 0.5 point if baseline EDSS score was ≥5.5, confirmed over 6 months. Other secondary endpoint was the proportion of patients who achieved NEDA-3 status (absence of clinical relapses, disability EDSS progression, and MRI disease activity as depicted by new/enlarging T2 lesions or Gadolinium enhancing T1 lesions). Adverse events also were recorded. RESULTS: A total of 195 RRMS patients (70% female) who started alemtuzumab treatment were included. Mean of follow-up was 2.38 years. Alemtuzumab significantly reduced the annualized relapse rate from baseline with risk reductions of 86%, 83.5%, and 84%, at 12, 24, and 36 months of follow-up respectively (Friedman test, p-value < 0.05 for all comparisons). Alemtuzumab also significantly reduced EDSS score over one and two years after starting alemtuzumab treatment (Friedman test, p-value<0.001 for both comparisons). A high proportion of patients presented confirmed 6-month stability or disability improvement (92%, 82%, and 79%, over 1, 2 and 3 years of follow-up respectively). The proportion of patients who retained NEDA-3 status at 12, 24 and 36 months were 61%, 49%, and 42%, respectively. Baseline characteristics associated with a lower probability of achieving NEDA-3 were younger age, sex female, high ARR, elevated number of previous treatments, and switch from a second line therapy. Infusion related reactions were the most frequent adverse event observed. The most common infections were urinary tract infections (50%), and upper respiratory tract infections (19%) over the 3 years of follow- up. Secondary thyroid autoimmunity was developed in 18.5% of patients. CONCLUSION: Alemtuzumab has demonstrated in real clinical practice high effectiveness in controlling multiple sclerosis activity, and no unexpected adverse events were observed.

Self-perception of dual career barriers and athletic identity in student-athletes with disabilities according to disability type and level of professionalization.

The objective of this study was to analyze the perceived barriers to dual career success and athletic identity of student-athletes according to disability type and level of professionalization. The final sample consisted of 203 student-athletes with disabilities from five European countries. The questionnaires used were ESTPORT, EBBS and AIMS. Depending on disability type, it was found that student-athletes with hearing and physical impairment showed the highest difficulty in reconciling sports and studies (p = 0.001); that student-athletes with a hearing impairment showed the highest score in the barrier 'the cost of education is high' (p = 0.023); that student-athletes with a physical impairment had the highest scores in the barrier 'Exercise tires me' (p = 0.013); that student-athletes with cerebral palsy showed the highest scores in the barrier 'I do not have enough university/educational institution support' (p = 0.014) and 'Exercise facilities do not have convenient timetables for me' (p = 0.001). Depending on sports professionalization level, semi-professional student-athletes showed the highest values in the barrier 'the university/educational institution is far from my training center' (p = 0.040); while professional student-athletes had the highest score in the barrier 'exercise takes too much time from family responsibilities' (p = 0.034). In most of the variables related to identity as athletes, professional student-athletes showed the highest values, followed by semi-professional athletes (p = 0.043- < 0.001). In conclusion, the self-perception of barriers is quite relevant, with differences arising from disability type and level of professionalization, whereas the identity as an athlete is only different according to the level of professionalization.

Analysis of direct, indirect, and intangible costs of epilepsy.

INTRODUCTION: A financial estimate has been made of the costs of epilepsy in adults. METHODS: A prospective, observational study, over a period of 6 months, on epileptic patients over 14 years-old. Patients with concomitant diseases that could influence the outcome of the epilepsy were excluded. The direct costs included: treatment received, number of visits to neurology, primary care, and emergencies, number of days admitted to hospital, number and type of diagnostic tests, use of transport to and from hospital, and psychopedagogic and social support due to the epilepsy. The indirect costs were analysed according to, loss of work productivity of the patients, taking into account families where the patient needed supervision due to epilepsy. The total costs were derived from the sum of the direct and indirect costs. The intangible costs were calculated according to QOLIE-10 questionnaire. RESULTS: The mean direct cost per patient was 1,055.2 €. The mean indirect financial costs came to 1,528.8 € per patient. The total cost associated to epilepsy was a mean of 2,584 € for each patient, mainly arising from loss of work days (p<.05). For intangible costs according to the QOLIE-10 scale a mean of 77.8 was obtained. CONCLUSIONS: The greatest percentage of costs associated to epilepsy is due to the work productivity loss by the patients. The costs of psychological and social suffering in epilepsy lead to a deterioration in the quality of life.

Progression of a series of patients with relapsing-remitting multiple sclerosis treated for 7 years with natalizumab using the "no evidence of disease activity" parameter.

INTRODUCTION: The safety and effectiveness of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in clinical trials. However, due to the limitations of these trials, it is important to know how the condition behaves under long-term clinical practice conditions. OBJECTIVE: To determine the long-term effectiveness of natalizumab in patients with RRMS by means of annual evaluation of the "no evidence of disease activity" (NEDA) parameter, which includes number of relapses, disability (measured with the Expanded Disability Status Scale), and brain MRI parameters. PATIENTS AND METHODS: We performed a retrospective study of patients with RRMS from 3 centres who were treated with one or more doses of natalizumab. Each year, we evaluated NEDA status and safety based on the percentage of patients who discontinued treatment with natalizumab and experienced adverse reactions. RESULTS: The study included 89 patients, most of whom received treatment for 2 to 4 years, with a follow-up period of up to 7 years. Natalizumab significantly reduces the radiological and clinical progression of the disease, as well as the annual rate of relapses. The NEDA parameter demonstrates the effectiveness of the drug, with values of 75.28% for year one and 66.67% for year 7. Twenty-five patients (28.1%) dropped out after a median of 4 years. Fourteen of these patients (56%) dropped out due to the appearance of anti-JC virus antibodies, either in isolation or associated with another cause. Four dropouts (16%) were due to treatment ineffectiveness, with one patient dying due to progressive multifocal leukoencephalopathy. CONCLUSIONS: Natalizumab is highly effective as measured by the NEDA long-term remission parameter.

Four-year safety and effectiveness data from patients with multiple sclerosis treated with fingolimod: The Spanish GILENYA registry.

OBJECTIVE: To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. METHODS: An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. RESULTS: Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continued to be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs. CONCLUSIONS: The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance.

Perampanel effectiveness and safety as early add-on treatment for focal-onset seizures: PEREAGAL study.

BACKGROUND: Perampanel (PER) is an effective adjunctive therapy for controlling focal-onset seizures (FOS), but few studies have examined its effects as an early add-on for the treatment of FOS in daily clinical practice. METHODS: Our retrospective, multicenter, observational study evaluated the effectiveness and safety of PER as an early add-on in 77 patients with FOS, with and without focal to bilateral tonic-clonic seizures (FBTCS) after 3, 6 and 12 months in a real-world setting. RESULTS: After 12 months of treatment (median dose 6 [4,8] mg/day), the retention rate was 79.2 % and 60 % of patients (39/65) experienced a ≥50 % reduction in seizure frequency relative to baseline. The seizure-free rate was 38.5 % for all seizures (25/65) and 60 % for FBTCS (12/20). The responder rate at 12 months was significantly higher when PER was given with one concomitant AED (72.2 %) compared to when PER was given with two concomitant AEDs (44.8 %). Drug-related adverse events (AEs) were reported in 40.3 % of patients, most of them being mild (64.2 %). Twelve patients (15.6 %) discontinued treatment because of AEs. CONCLUSIONS: PER is an effective and safe early add-on for patients with refractory FOS, especially for those with FBTCS.

[Association of paracoccidioidomycosis with different pulmonary pathologies in a hospital in Corrientes Province, Argentina]. / Paracoccidioidomicosis asociada a otras patologías respiratorias en un hospital de Corrientes, Argentina.

For 2 years, a systematic research of paracoccidioidomycosis (PCM) had been conducted in a hospital in the city of Corrientes. The inclusion criterium used was: tuberculosis patients (TBC), presumptive or confirmed diagnosis of pulmonary cancer (CA), chronic obstructive pulmonary disease (COPD) and/or X-ray images compatible with pulmonary mycosis (XRC). Eighty four patients were studied: 57 (TBC), 1 (CA), 5 (COPD), 3 (TBC+CA), 4 (TBC+COPD), 4 (COPD+CA) and 10 (XRC). Serology tests by agar gel immunodiffusion (IDGA) were performed on all patients, whereas microbiological studies were performed on those cases in which clinical samples could be obtained. Ten PCM were diagnosed by IDGA; 4 associated to TBC, 1 to TBC+CA, 3 to COPD and only 2 to XRC. PCM was mycologically proven in 9 of these cases. Systematic research of PCM would lead to an early diagnosis and therefore, to better chances for a successful treatment.

[Leber's optic neuropathy: a case report]. / Neuropatía óptica de Leber: caso clínico.

INTRODUCTION: Leber's optic neuropathy is a hereditary disease that mainly affects young males and is produced by specific mutations of the mitochondrial DNA, which affect the complex I of the mitochondrial respiratory chain. CASE REPORT: An 18-year-old male who presented with a 3-week history of progressive loss of sight in the right eye. Magnetic resonance imaging of the brain revealed numerous hyperintense lesions in the periventricular and subcortical white matter, and the visual evoked potentials showed bilateral optic neuropathy that was mild on the left side and severe on the right side. A spinal tap was performed and oligoclonal bands were detected in the cerebrospinal fluid. In the weeks that followed vision continued to get worse on both sides and the patient had hyalinised vessels in the papilla, with lower amplitude responses bilaterally in the electroretinogram. A genetic study was conducted that revealed a primary mutation 11778 in gene MTND4 and secondary mutation 15257 in gene MTCYB, which were compatible with a diagnosis of Leber's optic neuropathy. CONCLUSIONS: The absence of inflammation of the optic disc, which could lead to the suspicion of a retrobulbar neuritis, must act as a warning to the physician that he or she is possibly before a case of Leber's optic neuropathy, especially when the loss of vision is still progressing, when there is early bilateral involvement or if there is a family history of optic neuritis or multiple sclerosis.

Evolución de una serie de pacientes con esclerosis múltiple remitente-recurrente tratados con natalizumab durante 7 años mediante el parámetro no evidencia enfermedad activa / Progression of a series of patients with relapsing-remitting multiple sclerosis treated for 7 years with natalizumab using the “no evidence of disease activity” parameter

Introducción: La efectividad y seguridad de natalizumab en pacientes con esclerosis múltiple remitente recurrente (EMRR) se demostró en ensayos clínicos. Sin embargo, por las limitaciones de estos es importante saber cómo se comporta en condiciones de práctica clínica a largo plazo.ObjetivoConocer la eficacia a largo plazo de natalizumab en pacientes con EMRR mediante la evaluación anual del no evidence of disease activity (NEDA), que incluye número de brotes, discapacidad medida con EDSS y parámetros de RM cerebral.Pacientes y métodosEstudio retrospectivo y multicéntrico (n = 3) de pacientes con EMRR tratados con una o más dosis de natalizumab. Se evaluó el estado NEDA cada año y la seguridad a partir del porcentaje de pacientes que discontinuaron y que presentaron efectos adversos.ResultadosIncluimos 89 pacientes, la mayoría recibieron tratamiento durante 2 a 4 años, con una duración del seguimiento de hasta 7 años. Natalizumab reduce significativamente la progresión radiológica y clínica de la enfermedad, así como la tasa anual de brotes, demostrándose su eficacia con el parámetro NEDA, 75,28% al primer año y 66,67% al séptimo año. Veinticinco pacientes (28,1%) han abandonado el estudio en una mediana de tiempo de 4 años, 14 pacientes (56%) por aparición de anticuerpos contra el virus JC, como causa única o asociada a otro motivo, 4 abandonos (16%) fueron por ineficacia, un paciente falleció a causa de LMP.ConclusionesNatalizumab presenta una alta eficacia medida mediante el parámetro de remisión NEDA a largo plazo. (AU)

Introduction: The safety and effectiveness of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in clinical trials. However, due to the limitations of these trials, it is important to know how the condition behaves under long-term clinical practice conditions.ObjectiveTo determine the long-term effectiveness of natalizumab in patients with RRMS by means of annual evaluation of the “no evidence of disease activity” (NEDA) parameter, which includes number of relapses, disability (measured with the Expanded Disability Status Scale), and brain MRI parameters.Patients and methodsWe performed a retrospective study of patients with RRMS from 3 centres who were treated with one or more doses of natalizumab. Each year, we evaluated NEDA status and safety based on the percentage of patients who discontinued treatment with natalizumab and experienced adverse reactions.ResultsThe study included 89 patients, most of whom received treatment for 2 to 4 years, with a follow-up period of up to 7 years. Natalizumab significantly reduces the radiological and clinical progression of the disease, as well as the annual rate of relapses. The NEDA parameter demonstrates the effectiveness of the drug, with values of 75.28% for year one and 66.67% for year 7. Twenty-five patients (28.1%) dropped out after a median of 4 years. Fourteen of these patients (56%) dropped out due to the appearance of anti–JC virus antibodies, either in isolation or associated with another cause. Four dropouts (16%) were due to treatment ineffectiveness, with one patient dying due to progressive multifocal leukoencephalopathy.ConclusionsNatalizumab is highly effective as measured by the NEDA long-term remission parameter. (AU)

[Fingolimod: effectiveness and safety in routine clinical practice. An observational, retrospective, multi-centre study in Galicia]. / Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Galicia.

INTRODUCTION: The effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) have been proven in clinical trials. Yet, due to their limitations, it is important to know how it behaves under everyday clinical practice conditions. Hence, the aim of this study is to evaluate the effectiveness and safety of fingolimod after 12 months' usage in clinical practice in Galicia. PATIENTS AND METHODS: We conducted a retrospective, multi-centre study (n = 8) of patients with RRMS who were treated with one or more doses of fingolimod, 0.5 mg/day. Effectiveness was assessed -annualised relapse rate (ARR), changes in the score on the Expanded Disability Status Scale (EDSS), percentage of patients free from relapses, free from progression of disability and free from activity in resonance- for the total number of patients and according to previous treatment. Safety was assessed based on the percentage of patients who withdrew and presented adverse side effects. RESULTS: After 12 months' use, fingolimod reduced the ARR by 87% (1.7 to 0.23; p < 0.0001) and, consequently, 81% of patients were free from relapses. The score was reduced by 9%. In all, 91% of patients were free from progression of disability and 72% were free from resonance activity. No signs of disease activity were found in 43% of the patients. Most of the benefits of fingolimod differed depending on previous treatment. About a third of the patients reported adverse side effects, but only 2% of them withdrew for this reason. CONCLUSIONS: In clinical practice, most of the results on the effectiveness of the clinical trials conducted with fingolimod were observed during the first 12 months of treatment. A better safety profile was observed than that reported in the clinical trials.

TITLE: Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Galicia.Introduccion. La efectividad y seguridad del fingolimod en pacientes con esclerosis multiple remitente recurrente (EMRR) se demostro en ensayos clinicos. Sin embargo, por las limitaciones de estos, es importante saber como se comporta en condiciones de practica clinica habitual. Asi, el objetivo de este estudio es evaluar la efectividad y seguridad del fingolimod despues de 12 meses de uso en la practica clinica en Galicia. Pacientes y metodos. Estudio retrospectivo y multicentrico (n = 8) de pacientes con EMRR y tratados con una o mas dosis de fingolimod, 0,5 mg/dia. Se evaluo la efectividad ­tasa anualizada de brotes (TAB), cambio en la puntuacion de la escala expandida del estado de discapacidad (EDSS), porcentaje de pacientes libres de brotes, libres de progresion de discapacidad y libres de actividad en resonancia­ para el total de pacientes y segun tratamiento previo. Se evaluo la seguridad a partir del porcentaje de pacientes que discontinuaron y que presentaron efectos adversos. Resultados. Despues de 12 meses de uso, el fingolimod redujo un 87% la TAB (de 1,7 a 0,23; p < 0,0001) y, en consecuencia, un 81% de pacientes estuvo libre de brotes. La puntuacion de la EDSS disminuyo un 9%. Un 91% de pacientes estuvo libre de progresion de discapacidad y un 72%, libre de actividad en resonancia. En el 43% de los pacientes no se evidenciaron signos de la actividad de la enfermedad. La mayoria de los beneficios del fingolimod difirieron segun el tratamiento previo. Alrededor de un tercio de los pacientes comunicaron efectos adversos, pero solo el 2% discontinuo debido a ellos. Conclusiones. La mayoria de los resultados de efectividad de los ensayos clinicos del fingolimod se observa durante los 12 primeros meses de tratamiento en la practica clinica. Se observo un mejor perfil de seguridad al comunicado en los ensayos clinicos.

[The economic impact of epilepsy]. / Impacto económico de la epilepsia.

AIMS: In this study we review the economic impact involved in suffering from this disease in an attempt to determine how it affects both the individual and society, and the potential benefits deriving from its prevention and treatment. DEVELOPMENT: The World Health Organisation and the World Bank have pointed out that 90% of the costs generated by epilepsy are produced in developing countries. Yet in most developed countries the economic impact of the disease remains partially hidden for patients by the existence of publicly funded health service. As regards spending on pharmaceutical products in Spain, the subgroup made up of the antiepileptic drugs accounted for 1.36% of the total spending throughout the year 2001. Nevertheless, the main economic consequence for most patients is the limitation they suffer in their occupational activities, which is inversely proportional to the degree of control over their seizures and considerably higher than in the general population. Moreover, in epilepsy we must not forget the costs linked to its numerous psychological and social consequences. CONCLUSIONS: As happens in other areas of health care, the way epilepsy is attended depends to a large extent on economic factors. Further studies are therefore needed to provide us with a better understanding of the role played by economics in the field of health care.

[Cerebellar glioblastoma multiforme: a case report]. / Glioblastoma multiforme de cerebelo: caso clínico.

INTRODUCTION: Cerebellar glioblastoma multiforme (CGM) accounts for less than 1% of all intracranial glioblastomas; it spreads quickly locally, above all towards the brain stem and adjacent leptomeninges, and has a poor prognosis. CASE REPORT: We report the case of a 55 year old patient who presented a continuous feeling of dizziness, instability and sickness, with occasionally vomiting and double vision that had started two months before being admitted to hospital. A physical exploration revealed hypaesthesia of the right side of the face, tactile and algesic hypaesthesia in the left side of the body and nystagmus in the bilateral horizontal gaze. Results of the general physical exploration were normal. A magnetic resonance (MR) brain scan revealed a 3 cm expansive lesion in the middle cerebellar peduncle and right cerebellar hemisphere, which was hypointense in T1 and hyperintense in T2. Administering contrast showed it to be heterogeneous, with irregular annular enhancement, and perilesional edema. Subtotal excision of the lesion was performed and pathological analysis allowed a diagnosis of glioblastoma multiforme to be made; radio and chemotherapy were continued. CONCLUSION: CGM is infrequent and 46.7 years is the mean age of onset. 59% of tumours are located in the hemispheres, they tend to spread locally, and remote metastases have also been reported. Initial clinical manifestations are intracranial hypertension, and gait and balance disorders. Differential diagnosis is provided by MR and includes metastasis, infarction and abscesses. Treatment involves radical surgical excision followed by local radiotherapy. The use of chemotherapy has been reported but its role in the treatment of this entity is still not altogether clear.

[Cerebral atrophy in multiple sclerosis patients treated periodically with boluses of methylprednisolone]. / Atrofia cerebral en pacientes con esclerosis múltiple tratados con bolos periódicos de metilprednisolona.

INTRODUCTION: In the last years advances in the treatment of the remittant and secondary progressive forms of the multiple sclerosis (MS) have taken place. In the primary progressive forms (PP) the side effects of potentially useful drugs prevent their use; in some studies an improvement of the evolution with the intravenous administration of periodic pulses of methylprednisolone (MP) has been observed. OBJECTIVE: To evaluate if periodic pulses of intravenous MP injected every 4-6 weeks increase the degree of cerebral atrophy of the patients with PP MS. PATIENTS AND METHODS: We studied 11 patients with PP MS treated during 33 months with periodic pulses of intravenous MP. The degree of cerebral atrophy was evaluated in axial cuts of 10 mm of studies of magnetic resonance with the indices of Evans, bicaudate, bifrontal, frontal spears and bithalamic. The statistical evaluation of the results was made applying the test of Wilcoxon-Mann-Whitney. RESULTS: There are not statistically significant differences in the degree of cerebral atrophy with any of the used indices. CONCLUSIONS: Periodic pulses of intravenous MP do not accelerate the cerebral atrophy in patients with progressive forms of multiple sclerosis.

[Acute complications of diabetes mellitus]. / Complicações Agudas da Diabetes Mellitus.

A retrospective study was made of 83 diabetic patients admitted to the Department of Internal Medicine between January 1986 and December 1993, with acute intercurrence of the disease. The authors considered some clinical features (age, type and frequency of complication, form of presentation, causal aetiology, laboratory findings and therapeutic options). Statistical relationships between different populations were made using the unpaired Student's T. method. Results were compared with those in the literature, leading to some significant conclusions.

Efficacy of intravenous lacosamide as an add-on treatment in refractory status epilepticus: a multicentric prospective study.

OBJECTIVE: Treatment of status epilepticus (SE) has not changed in the last few decades, benzodiazepines plus phenytoin or valproate being the most common treatment. Once this first and second line treatment has failed SE is considered refractory (RSE). This study aimed to assess the efficacy and tolerability of intravenous (iv) lacosamide (LCM) in RSE. METHOD: Patients with RSE who were treated with ivLCM in six Spanish centers were prospectively included. Efficacy was defined as cessation of seizures after starting ivLCM, with no need for any further antiepileptic drug. All patients had been unsuccessfully treated following the standard protocol (benzodiazepines plus phenytoin or valproate) before ivLCM was added. RESULTS: Thirty-four patients were included, 52.9% men, with mean age of 60.15 years. In 58.9% of patients the etiology was symptomatic, and the most common type of SE was focal convulsive (82.4%). Mean initial bolus dose of LCM was 323.53mg. ivLCM was effective in more than half of patients (64.7%), with termination of SE before 12h in 50% of them. ivLCM was used as a fourth or later option in 76.5% of patients. No serious adverse events attributable to LCM were reported. CONCLUSIONS: LCM might be a fast, effective and safe add-on treatment in RSE.

Adaptación cultural y validación al español de España del MSTCQ© (Multiple Sclerosis Treatment Concerns Questionnaire) / Cultural adaptation and validation of a peninsular Spanish version of the MSTCQ© (Multiple Sclerosis Treatment Concerns Questionnaire)

Introducción: A pesar de la efectividad de los tratamientos inyectables para la esclerosis múltiple (EM), las reacciones adversas y el dolor pueden implicar problemas de satisfacción y adherencia. Se presenta la validación de la versión española del Multiple Sclerosis Treatment Concerns Questionnaire (MSTCQ)©, que evalúa la satisfacción con el dispositivo de autoinyección (DA), 4 dimensiones: sistema de inyección (A), efectos secundarios (B) (síntomas pseudogripales, reacciones, satisfacción), experiencia con el tratamiento (C) y beneficios (D). Métodos: Dos fases de estudio: 1) Adaptación cultural con expertos (n = 6) y pacientes (n = 27). 2) Estudio observacional, transversal y multicéntrico de validación. Se evaluaron 143 pacientes adultos con EM que utilizaban el DA Extavijec(TM) 30G. Cuestionarios: MSTCQ©; Patient-Reported Indices for Multiple Sclerosis (PRIMUS©), y Treatment Satisfaction Questionnaire for Medication (TSQM©). Propiedades psicométricas: factibilidad (% casos válidos y distribución de puntuaciones); fiabilidad (α-Cronbach) y test-retest (n = 41, coeficiente correlación intraclase [CCI]), y validez de constructo (análisis factorial A y B, [AF]) y convergente (Spearman-rho MSTCQ© versus TSQM©). Resultados. Edad media (DT) 41,94 (10,47) años, 63% mujeres, 88,11% con EM remitente-recurrente, media (DT) EDSS 2,68 (1,82) puntos. Alta cumplimentación del MSTCQ© (perdidos 0-2,80%). Alta consistencia interna: puntuación total (A + B) α = 0,89, por dimensiones (A, B y C) α = 0,76, 0,89 y 0,92, respectivamente. Excelente concordancia test-retest en las puntuación total (CC I= 0,98), por dimensiones (A, B y C) CCI = 0,82, 0,97 y 0,89, respectivamente. El AF corroboró la estructura interna del cuestionario original. Correlación moderada (Rho = 0,42-0,74) y significativa (p < 0,05 y p < 0,01) entre las puntuación total y por dimensiones del MSTCQ© y el TSQM©. Conclusiones. Se constatan adecuadas propiedades psicométricas de la versión española del MSTCQ

Introduction: Although subcutaneous treatments for multiple sclerosis (MS) have been shown to be effective, adverse reactions and pain may adversely affect treatment satisfaction and adherence. This study presents an adapted and validated Spanish version of the Multiple Sclerosis Treatment Concerns Questionnaire© (MSTCQ), which evaluates satisfaction with the injection device (ID) across 4 domains: injection system (A), side effects (B) (flu-like symptoms, reactions, and satisfaction), experience with treatment (C) and benefits (D). Methods: Two study phases: 1) Cultural adaptation process with input from experts (n = 6) and patients (n = 30). 2) Validation obtained by means of an observational, cross-sectional, multi-centre study evaluating 143 adult MS patients using an ID. Tools employed: MSTCQ©, Patient-Reported Indices for Multiple Sclerosis (PRIMUS©), and Treatment Satisfaction Questionnaire for Medication (TSQM©). Psychometric properties: Feasibility (percentage of valid cases and floor/ceiling effects); Reliability (Cronbach α) and test-retest correlation (n = 41, intraclass correlation coefficient, ICC); and construct validity (factor analysis of domains A and B) and convergent validity (Spearman rank-order correlation for MSTCQ© vs TSQM©). Results: Mean age (SD) was 41.94 (10.47) years, 63% of the group were women, and 88.11% presented relapsing-remitting MS. Mean (SD) EDSS score was 2.68 (1.82) points. MSTCQ© completion was high (0%-2.80% missing data). Internal consistency was high at α=0.89 for the total score (A+B) and α = 0.76, 0.89, and 0.92 for domains A, B, and C, respectively. The version demonstrated excellent test-retest reliability for the total (ICC = 0.98) and for domains A, B, and C: ICC = 0.82, 0.97, and 0.89, respectively. Factor analysis corroborated the internal structure of the original questionnaire. The association between total and domain scores on both the MSTCQ© and the TSQM© was moderately strong (Rho = 0.42-0.74) and significant (P < .05 and P < .01). Conclusion: The Spanish version of MSTCQ© demonstrates appropriate psychometric properties