Rebound after discontinuation of teriflunomide in patients with multiple sclerosis: 2 case reports.

Teriflunomide is an oral first-line disease modifying treatment (DMT) for patients with relapsing-remitting multiple sclerosis (RRMS). It can take up to two years to achieve systemic clearance of teriflunomide to an acceptable level, but this washout period may be accelerated by administration of cholestyramine. Relapse of multiple sclerosis (MS) during washout of teriflunomide or other first-line DMT is not as common. We report two patients with RRMS who experienced a relapse after the accelerated elimination period (AEP) of teriflunomide and confirmation of negative plasmatic levels (<0.02 µg/ml). In cases of risk of MS activity, we should not wait for teriflunomide negative plasmatic levels confirmation before starting the next DMT to reduce the risk of relapse.

[Vitiligo with Koebner phenomenon in a patient with multiple sclerosis treated with alemtuzumab]. / Vitiligo con fenomeno de Koebner en una paciente con esclerosis multiple tratada con alemtuzumab.

TITLE: Vitiligo con fenomeno de Koebner en una paciente con esclerosis multiple tratada con alemtuzumab.

[Clinical features of familial Creutzfeldt-Jakob disease and the E200K mutation in Spain]. / Características clínicas de la enfermedad de Creutzfeldt-Jakob familiar y mutación E200K en España.

INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is an infrequent pathology affecting the central nervous system (about 1/1,000000) that has a subacute progression and, for the time being, a fatal prognosis. The familial forms account for between 5-10% of cases and one of the most frequent is that produced by the E200K mutation of prion protein gene (PRNP), which has not been reported in Spanish families although Spain is considered to be part of the expansion circuit of the mutation. CASE REPORTS: We report on a Spanish family with three cases of CJD. The disease affected three females (our patient and two paternal aunts), who started with dementia, myoclonias, gait disorders and cortical blindness at the ages of 61, 53 and 55 years. Progress in all three cases was torpid and the symptoms advanced in a short time. Results of the complementary tests that were carried out were normal, except for the electroencephalogram, which was compatible with CJD in all three cases, and the imaging tests, which revealed cortical-subcortical atrophy. A confirmatory diagnosis was reached from a biopsy, the clinical picture and the family history in the cases of the paternal aunts and from a genetic study of our patient, which confirmed the E200K mutation. CONCLUSIONS: This family confirms the presence of familial forms of CJD in Spain, more specifically the E200K mutation, and highlights the role of Spain in the possible transmission of this mutation.

[The efficiency and cost-utility ratio of interferon beta in the treatment of multiple sclerosis in Andalusia]. / Eficiencia y relación coste-utilidad del interferón beta en la esclerosis múltiple en Andalucía.

INTRODUCTION: The availability of the interferon beta in its three forms at the moment available in our country and of glatiramer acetate has marked a point of flexion in the natural history of multiple sclerosis (MS), but the high cost of these treatments cause that its use is questioned. In this work we have studied the effectiveness and efficiency of the processing with interferon beta, and the cost-utility of these treatments in MS in Spain has been also analyzed. PATIENTS AND METHODS: For this work we studied 102 patients affected of RR MS, treated with the three interferons beta which we have available in our country. We used as control 330 patients who had participated in the pivotal clinical interferon trials with both interferon beta 1a. In these patients in addition to effectiveness data, we have studied the disability measured as area below curve and the quality of life (AVACs). We also calculated the economical costs, considering the relation cost-utility in our country. RESULTS: Besides to confirm the data of effectiveness of three interferons, in this study a saving of 23 days/year is demonstrated what corresponds to 0.063 AVACs. The additional cost of interferons is greater than the avoided cost until the fifth year of treatment in which the tendency is reversed in favor of the group of treated patients, if we assume that the same effectiveness that we found in the first years is maintained in the long term. CONCLUSION: The use of the treatment with interferon beta is justified by its effectiveness, efficacy and efficiency. The additional cost of the treatment will be compensated in the long term if the effectiveness of the interferon beta is maintained.

[The use of magnetic resonance imaging in the study of asymptomatic familial multiple sclerosis patients]. / Estudio de pacientes asintomáticos de esclerosis múltiple familiar mediante resonancia magnética.

INTRODUCTION: Multiple sclerosis (MS) is the neurological non-traumatic disease that produces permanent incapacity in the young people with the greatest frequency. An almost total consensus exists on the implication of environmental and genetic factors in the pathogenesis of the disease. In a considerable percentage of patients, antecedent relatives of other cases of MS exist, who are separated by other healthy relatives sometimes. AIMS: We try to study the familial antecedents of the MS patients, to locate to the healthy members of the family including in the forced line of the possible genetic transmission of the disease and ruling out subclinical involvement by the use of magnetic resonance imaging (MRI). PATIENTS AND METHODS: We reviewed the familial antecedents of the MS patients followed by the MS Unit of the Service of Neurology of the Hospital Virgen Macarena of Seville. After the accomplishment of their genealogical trees, we identified the cases of familial MS. We locate and practice MRI on the healthy subjects of the family, who are in the genetic line of communication of the disease (obligate carriers). RESULTS AND CONCLUSIONS: We were able to identify 14 obligate carriers of the gene in 12 of the families. In the MRIs that were done, we found MS-compatible lesions in 10 subjects. These findings confirm the existence of silent forms of the disease, that make difficult the knowledge of the genetic implications in the pathogenesis of the disease.

[Clinical evaluation of multiple sclerosis: quantification by use of scales]. / Evaluación clínica de la esclerosis múltiple: cuantificación mediante la utilización de escalas.

INTRODUCTION: Clinical evaluation is indispensable in multiple sclerosis (MS) for the quantitative measurement of the extent of the disorder, which is in turn required to find out how the disease is evolving and the influence the different forms of treatment are having on it, both in the experimental phase and in the usual monitoring they are subjected to. METHOD: We review the different scales that are used to evaluate the distinct symptomatic and functional aspects of MS and the repercussions these have on the extent of disability displayed in the patient s social and personal life. Although in recent years, the EDSS has been an essential, irreplaceable scale in MS, other instruments of measurement that complement it have also begun to appear. The fatigue, cognitive function and quality of life scales are being used more and more frequently. The Multiple Sclerosis Functional Composite is an instrument that is used more and more frequently in MS and has proved to be highly sensitive in the evaluation of very important clinical trials. CONCLUSIONS: The lack of correlation between the distinct scales corroborates the fact that they measure complementary aspects of MS.

[Immunosuppressants and multiple sclerosis]. / Inmunosupresores y esclerosis múltiple.

AIMS: Technological progress, improvements in the design of clinical trials and in MRI have led to a great variety of therapeutical approaches in dealing with multiple sclerosis (MS), some of which have been successful while others less so, despite promising results from animal models. DEVELOPMENT: In this paper we review the present state of therapy with immunosuppressants in MS and special attention is paid to trials conducted with cladribine, linomide, sulfasalazine, ciclophosphamide, mitoxantrone, cyclosporine A and azatioprine. CONCLUSION: Severe, unspecific immunosuppression lowers the anatomopathological and clinical activity of the disease, with slight improvements in the seizure rates and the MRI. While no effects have been found on the progression, serious short and long term side effects have been observed which, in some cases, prevent it from being administered. However, it is true that proof of the efficiency of these products may not have been possible owing to methodological problems they might be more useful alone or in combination with immunomodulators.

Inmunosupresores y esclerosis múltiple / Immunosuppressants and multiple sclerosis

Objetivo. Los avances tecnológicos y las mejoras en el diseño de los ensayos clínicos y en la RM han conducido a una gran variedad de aproximaciones terapéuticas a la esclerosis múltiple (EM), algunas de ellas con éxito, mientras que otras no lo han sido tanto, a pesar de los prometedores resultados en modelos animales. Desarrollo. En este artículo revisamos el estado de la terapia con inmunosupresores en la EM y prestamos especial atención a los ensayos realizados con cladribina, linomide, sulfasalacina, ciclofosfamida, mitoxantrona, ciclosporina A y azatioprina. Conclusión. Una inmunosupresión grave e inespecífica disminuye la actividad anatomopatológica y clínica de la enfermedad, con modestos beneficios en las tasas de ataques y la RM, pero no se han demostrado efectos sobre la progresión y sí la existencia de serios efectos secundarios a corto y largo plazo que impiden, en algunos casos, su administración, aunque bien es verdad que la demostración de la eficacia de estos productos puede no haberse conseguido por problemas metodológicos; posiblemente son más útiles solos o combinados con inmunomoduladores (AU)

Intrathecal IgG synthesis: marker of progression in multiple sclerosis patients.

OBJECTIVES: We study the power of IgG synthesis value as a marker of disease activity in multiple sclerosis (MS). MATERIAL AND METHODS: Link index was calculated in 202 MS patients. Time between first, second and third attack and progression index (PI) were compared in patient with normal (NLI) high (HL) or very high Link index (VHLI). RESULTS: Secondary progressive (SP) patients had a higher LI than relapsing-remitting (RR) and primary progressive (PP) courses (1.10 +/- 0.5 for SP vs 0.86 +/- 0.5 for RR and 0.81 +/- 0.5 for PP, P=0.01 and 0.03, respectively). Having a HLI in MS RR and SP patients has no time effect in the development of the second and third attack. PI was higher in patients with VHIL (0.67 +/- 0.7) vs patients with NLI (0.42 +/- 0.4, P=0.008) and with HLI (0.39 +/- 0.3, P=0.001). CONCLUSIONS: This study confirmed that LI is a good marker of subsequent progression of MS.