Switching from natalizumab to fingolimod: an observational study.

BACKGROUND: Multiple sclerosis patients who discontinue using natalizumab are at risk of a rebound in disease activity. However, the optimal alternative therapy is not currently known. AIMS OF THE STUDY: We report on clinical and MRI data and patient safety in a group of relapsing-remitting multiple sclerosis patients who tested seropositive for the JC virus and who have switched from natalizumab to fingolimod because of concerns regarding PML risks. METHODS: The test for JC virus antibodies was performed in 18 relapsing-remitting multiple sclerosis patients who were being treated with natalizumab for more than 1 year. Eight seropositive patients switched to fingolimod while the seronegative patients continued with natalizumab. RESULTS: After switching to fingolimod, five of eight patients (63%) experienced clinical relapses, and MRI activity was detected in six of eight patients (75%). Neither clinical relapses nor MRI activity was observed in the patients who continued with natalizumab. No serious adverse effects were detected. CONCLUSIONS: Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis, but its discontinuation continues to be a complex problem. All of the therapies tried thus far, including fingolimod, have been unable to control the reactivation of the disease. Further studies addressing alternative therapies after natalizumab discontinuation are necessary.

[Epidemiology of multiple sclerosis in Spain]. / Epidemiologia de la esclerosis multiple en España.

INTRODUCTION: Multiple sclerosis is a chronic autoimmune, inflammatory and neurodegenerative disease of the central nervous system and the most common non-traumatic disabling neurological disease in young adults. In the latest decades, multiple sclerosis is increasing worldwide, especially in women. The latitudinal distribution has been progressively attenuated. AIM: To review the epidemiological studies of multiple sclerosis in Spain to verify if this worldwide trend also occurs in Spain. DEVELOPMENT: We searched PubMed and Teseo databases using the search terms «epidemiology¼, «prevalence¼, «incidence¼, «multiple sclerosis¼ and «Spain¼. We selected articles published in Spanish and English between 1968 and 2018. CONCLUSIONS: Recent epidemiological studies confirm that Spain is a medium-high risk area for MS. The prevalence of MS has increased significantly throughout Spain in the latest years, especially in women, and recent studies show prevalence as high as 80-180 cases per 100,000.

TITLE: Epidemiologia de la esclerosis multiple en España.Introduccion. La esclerosis multiple es una enfermedad cronica autoinmune, inflamatoria y degenerativa del sistema nervioso central, y es el trastorno neurologico discapacitante no traumatico mas comun en adultos jovenes. Los estudios de prevalencia mas recientes indican que la frecuencia de la enfermedad ha aumentado en el mundo en las ultimas decadas, que dicho incremento de la prevalencia ocurre fundamentalmente a expensas de un mayor numero de casos de mujeres con formas remitentes, y que el gradiente latitudinal de la incidencia de la enfermedad se viene atenuando. Objetivo. Revisar los estudios sobre epidemiologia de esclerosis multiple en España para verificar si las tendencias mundiales se confirman en nuestro pais. Desarrollo. Busqueda bibliografica en las bases de datos PubMed y Teseo usando como palabras clave «epidemiology¼, «prevalence¼ e «incidence¼, cruzandolas con los terminos «multiple sclerosis¼ y «Spain¼; se realiza una seleccion inicial por titulo y resumen, en castellano e ingles, entre los años 1968 y 2018. Conclusiones. Un buen numero de estudios epidemiologicos recientes en España confirman que es una region de prevalencia media-alta de la enfermedad a lo largo de su geografia. Las cifras de prevalencia aumentan progresivamente a lo largo de las ultimas decadas hasta alcanzar en la actualidad 80-180 casos por 100.000 habitantes, y ello ha ocurrido a expensas de una mayor frecuencia de la enfermedad en las mujeres.

[Biomedical publications in Spain on debate (I): state of neurological journals]. / Las publicaciones biomédicas en España a debate (I): estado de las revistas neurológicas.

INTRODUCTION: Bibliometric studies belong to the so-called 'social studies of science', and science policy constitutes one of its main applied fields, providing objective and useful tools for evaluating the results of scientific activity. Neurological sciences are very important in the bibliometric map of Spain about biomedicine and health sciences, from a quantitative (second thematic area in productivity, only after biology-biochemical) and a qualitative (high health costs and morbimortality) point of view. DEVELOPMENT: In Spain we can found about 360 biomedical journals, 18 of them related to the area of neurological sciences. In 2005, only 17 biomedical Spanish journals were in the Science Citation Index database, three of them in the field of neurosciences: Neurologia (impact factor = 0.57), Revista de Neurologia (0.39) and Neurocirugia (0.23), and these journals have also very good Latindex criteria about formal aspects. But it is important to mention that the impact factor specifically measures visibility and diffusion of the works published by these journals rather than their scientific quality. We search the answer to some questions about the present and future of biomedical journals in general and neurological journals in particular: paper or electronic publication?, free access or open access?, scientific journal or scientific article?, English or Spanish publication? CONCLUSIONS: The Acuerdo de Buenos Aires is an initiative to promote scientific neurological papers of high quality in Spanish. The current status of neurological journals in the bibliometric context of our country is good and open to the advantages of electronic and free access.

[Biomedical publications in Spain on debate (II): the on-going 'revolutions' and their application to neurological journals]. / Las publicaciones biomédicas en España a debate (II): las 'revoluciones' pendientes y su aplicación a las revistas neurológicas.

AIM AND DEVELOPMENT: To debate about the application of on-going 'revolutions' in medical knowledge to Spanish neurological journals in the 21st century. This article reviews the current status of five revolutions in the field of health sciences, in general, and in neurological sciences, in particular: 1) the knowledge revolution: to translate the scientific investigation to the patient, with knowledge needs-driven research agenda with founder commissioning research to answer questions posed by clinicians, managers and patients, and systematic and critical appraisal reviews as the creator of quality improved knowledge; 2) the evidence based medicine revolution: the pyramid information of '4S', with systems (guidelines and computerized decision support systems), synopses (secondary journals), syntheses (systematic reviews and meta-analysis) and studies (original studies published in journals); 3) the web revolution: the possibility of dissemination of biomedical documentation by means of the Internet network are producing changes in the traditional way of conceiving scientific publication; the Internet represents a great advantage for investigation and also for clinical practice, since it permits free, universal access to databases and the interchange of texts, images and videos; 4) the open access revolution: to take full control over all operations related to the process of publish (to create, publish, communicate, distribute, reproduce and transform) with no need of any intermediaries, and to transform fundamental aspects concerning the circulation of knowledge, its use and availability; and 5) the librarian revolution: the project of a Virtual Health Library in Spain as a tool to access and disseminate scientific and technical knowledge on health through the Internet.

[Lumbar puncture: its indications, contraindications, complications and technique]. / Punción lumbar: indicaciones, contraindicaciones, complicaciones y técnica de realización.

INTRODUCTION: Although first described over 100 years ago, lumbar puncture is still an important tool in the diagnosis of neurological diseases. In this article we review its indications, contraindications, the technique for carrying it out, the analysis of the cerebrospinal fluid and possible complications. DEVELOPMENT: The lumbar puncture has diagnostic and therapeutic indications. The chief diagnostic indications include infectious, inflammatory and neoplastic diseases affecting the central nervous system. Complications are infrequent, except for headaches and low back pain, but can be severe. Analysis of the cerebrospinal fluid must include a cell count and determination of the glucose and protein concentrations. The other analytical studies of cerebrospinal fluid must be conducted according to the diagnostic suspicion. CONCLUSION: The lumbar puncture in expert hands is a safe test. The health professional should be suitably familiar with its contraindications, the regional anatomy and the technique used to perform it.

[Gender analysis of papers published in Revista de Neurología (2002-2006)]. / Análisis de género de los artículos publicados en Revista de Neurología durante el quinquenio 2002-2006.

INTRODUCTION: There is an ongoing interest in the society in promoting gender equality and in women integration in research activities. The purpose of this work is to identify from a gender perspective the bibliometric characteristics of articles published in Revista de Neurología journal during the 2002-2006 period. MATERIALS AND METHODS: Records were obtained from Science Citation Index database of ISI-Thomson platform. The following indicators were determined, disaggregated by gender: year of publication, type of document, number and order of signatures, number of collaborators, signature/papers index and in the institutional and geographical level. RESULTS: 4527 authors were identified, 2614 (57.74%) men and 1913 (42.,26%) women. The highest women's participation took place in original articles (39.01% of signatures). 44.5% of authors with one published article were women, while 'big women producers' (those with more than 9 articles) only were 16.67%. A greater productivity in men and a greater rate of collaboration in women has been detected. CONCLUSIONS: Scientific activity studies disaggregated by gender give an essential information in order to establish the basis of a scientific policy for promoting the woman as researcher. The evolution in the number of female authors in Revista de Neurología journal does not present an aiming growth to reach the parity in the next years. A low presence of women in positions of high productivity has been detected, whose causes should be identified.

[Preventive treatment with topiramate enhances the quality of life of patients with migraine]. / El tratamiento preventivo con topiramato mejora la calidad de vida de los pacientes con migrana.

INTRODUCTION: Topiramate has recently proved to be safe and effective in the prevention of migraine and is currently the only neuromodulatory drug indicated for the prevention of migraine in Spain. AIM: To evaluate the adherence, effectiveness and safety of preventive treatment with topiramate in patients diagnosed with migraine. PATIENTS AND METHODS: A prospective, observational, multi-centre study was conducted in general neurology departments. Patients eligible for the study were those with migraine, above 14 years of age, who needed preventive treatment and in whom other preventive treatments had failed or for whom topiramate was believed to be the most suitable therapy as regards its profile of side effects. The effectiveness of the treatment, patient satisfaction, side effects and loss of body weight were all evaluated. Effectiveness of the treatment was evaluated by means of the reduction in the frequency of migraines and the score obtained on the Headache Impact Test (HIT-6). RESULTS: A total of 79 patients were evaluated. The dosage of topiramate ranged between 25 and 200 mg/day, with an average of 100 mg/day. 19% of the patients dropped out of the study due to side effects. Paresthesias were the most frequent reason for dropping out. No serious side effects were observed. 14% of the patients lost more than 5% of the base weight. The percentage of patients who responded was 58%. The degree of satisfaction of the patients who completed the follow-up was: good (80%), regular (11%) and poor (9%). CONCLUSIONS: Preventive treatment with topiramate significantly reduces the impact of migraine and the disability that results from it. Treatment is satisfactory and improves the quality of life in a large percentage of patients.

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

INTRODUCTION: Post-authorisation studies are important to confirm whether the outcomes of clinical trials are reproduced in usual clinical practice. AIMS: To evaluate the effectiveness and safety of fingolimod in clinical practice in the province of Alicante. PATIENTS AND METHODS: A retrospective multi-centre study was conducted with remitting multiple sclerosis patients treated with fingolimod. Demographic, clinical and pharmacological data were collected. We report on the effectiveness of the drug -annualised relapse rate (ARR) and percentage of patients free from attacks- at one and at two years after treatment in relation to the previous year, and data concerning side effects are also provided. RESULTS: The sample consisted of 89 patients. Previous treatment was with immunomodulators (interferon beta or glatiramer acetate) in 54 patients and natalizumab in 32. Fifty patients changed due to failure with the immunomodulator and 31 owing to positive serology for JC virus (JCV+). Overall ARR decreased by 67.3% the first year (p < 0.0001) and by 84.1% the second (p = 0.0078). It diminished in patients with immunomodulator failure (85.6% the first year, p < 0.0001; 88.9% the second year, p = 0.0039) and increased in a non-significant manner in JCV+ patients in the first year. The percentage of patients free from relapses in the overall population increased from 32.6% to 68.1% in the first year (p < 0.0019) and to 82.6% in the second (p = 0.0215). This increase was not observed in JCV+ patients. Side effects were reported by 13 patients, which led to the drug being withdrawn in two of them. CONCLUSION: In clinical practice in the province of Alicante, levels of effectiveness and safety of fingolimod proved to be slightly higher than those found in clinical trials.

TITLE: Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en la provincia de Alicante.Introduccion. Los estudios postautorizacion son importantes para confirmar si los resultados de los ensayos clinicos se reproducen en la practica clinica habitual. Objetivo. Evaluar la efectividad y seguridad del fingolimod en la practica clinica en la provincia de Alicante. Pacientes y metodos. Estudio multicentrico retrospectivo de pacientes con esclerosis multiple remitente tratados con fingolimod. Se recogen las caracteristicas demograficas, clinicas y farmacologicas. Se describe la efectividad del farmaco ­tasa anualizada de brotes (TAB) y porcentaje de pacientes libres de brotes­ al año y a los dos años de tratamiento en relacion con el año previo y datos de efectos secundarios. Resultados. Se incluyo a 89 pacientes. El tratamiento previo fue inmunomodulador (interferon beta o acetato de glatiramero) en 54 pacientes y natalizumab en 32. Cincuenta pacientes cambiaron por fracaso con el inmunomodulador y 31 por serologia positiva del virus JC (VJC+). La TAB global disminuyo el 67,3% el primer año (p < 0,0001) y el 84,1% el segundo (p = 0,0078). Disminuyo en los pacientes con fracaso del inmunomodulador (el 85,6% el primer año, p < 0,0001; el 88,9% el segundo año, p = 0,0039) y aumento de forma no significativa en los pacientes VJC+ en el primer año. El porcentaje de pacientes libres de brotes en la poblacion global aumento del 32,6 al 68,1% en el primer año (p < 0,0019) y al 82,6% en el segundo (p = 0,0215). Este aumento no se observo en los pacientes VJC+. Trece pacientes tuvieron efectos secundarios, que obligaron a la retirada del farmaco en dos de ellos. Conclusion. En la practica clinica de la provincia de Alicante, el fingolimod mostro una efectividad y una seguridad ligeramente superiores a las de los ensayos clinicos.

[Generic drugs in the treatment of epilepsy]. / Fármacos genéricos en el tratamiento de la epilepsia.

AIM: We discuss some controversial aspects with prescription of generic drugs (GD) and the problems concerning bioequivalence, mainly in the case of drugs with non-linear pharmacokinetics and/or narrow therapeutic rank, like the antiepileptic drugs (AED). DEVELOPMENT: There is considerable debate about GD in the treatment of epilepsy, with clearly advantages (cost saving) and disadvantages (loss of seizure control or drug toxicity) in prescribing generics anticonvulsants. We make a systematic review of the literature in primary (PubMed) and secondary (Tripdatabase and Cochrane Library) bibliographic databases in relation to GD and AED. The main information is about classical AED (phenytoin, carbamazepine, valproic acid and primidone) and we don't found studies in this area about the new AED. The level of evidence is, generally, weak, based on case-series and expert opinion without explicit critical appraisal (except in phenytoin with level of evidence moderate, based on some analytical studies). In Spain, at this moment, there are only two generic AED, one-classical (carbamazepine) and one-new (gabapentin). CONCLUSION: The American Academy of Neurology and Epilepsy Foundation maintains that the individual and physician should be notified and give their consent before a switch in antiepileptic medications is made, whether it involves generic substitution for brand name products, or generic to generic substitutions.

Q fever mimicking herpetic encephalitis.

We describe a patient with temporal lobe encephalitis associated with primary Coxiella burnetii infection who presented with CT and MRI findings suggestive of herpes simplex encephalitis and an initial improvement during treatment with acyclovir. Q fever should be considered in the differential diagnosis of patients whose manifestations suggest herpes encephalitis.

Postural myoclonus induced by phenytoin.

Involuntary movements are an infrequent complication of treatment with phenytoin and include tremor, asterixis, myoclonus, parkinsonism, and dyskinesias. The mechanism by which phenytoin exerts its actions is unclear. Phenytoin has been observed to exert variable effects on dopamine metabolites and also may induce changes in serotonergic activity. In this report, we discuss the available experimental evidence concerning the possible mechanisms of involuntary movements induced by phenytoin. We describe a case of postural myoclonus during treatment with phenytoin.

Aggravation of parkinsonian tremor by cisapride.

Cisapride, a substituted piperidinyl benzamide that is chemically related to metoclopramide, is a prokinetic agent that facilitates motility of the gastrointestinal tract (1). The mechanism by which cisapride exerts its actions is not clear. It enhances acetylcholine release in the myenteric plexus of the gut, and evidence exists that it has an agonistic action on a serotonin receptor, probably the 5-HT4 receptor (2). The drug is well tolerated, and no central nervous system side effects have been reported. We describe two patients with parkinsonism who experienced aggravation of tremor while on therapy with cisapride.

Generalized spike-and-wave patterns in children: clinical correlates.

All electroencephalograms performed in our institution between 1980 and 1990 were reviewed. The clinical characteristics of children with epilepsy and generalized spike-and-wave (SW) patterns were analyzed. The SW patterns were classified according to their frequency. Electroencephalograms of 154 children with epilepsy revealed SW patterns. Absence seizures were the most common first seizure, but partial seizures were frequent. More than 40% had several types of seizures. Sixty percent of the epileptic syndromes were generalized, but almost 25% were partial. The typical SW pattern was associated with absence seizures, a normal examination and computed tomographic scan, idiopathic generalized epilepsies, monotherapy, freedom from seizures, and lack of recurrence. The slow SW pattern was associated with West syndrome; a younger age at seizure onset; atonic, myoclonic, tonic, and partial simple seizures; an abnormal examination and computed tomographic scan; cryptogenic or symptomatic generalized epilepsy or symptomatic partial epilepsy; polytherapy; and poor seizure control. The fast SW pattern was associated with secondary generalized, partial, tonic-clonic, and complex partial seizures; a normal computed tomographic scan; cryptogenic partial epilepsy; isolated seizures; and seizure recurrence. Epilepsy with a typical SW pattern should be considered benign, epilepsy with a slow SW pattern malignant, and epilepsy with a fast SW pattern treacherous.

[Paraneoplastic ataxia associated to anti CV2 antibodies]. / Ataxia paraneoplásica asociada a anticuerpos anti CV2.

INTRODUCTION: Anti CV2 antibodies are a type of paraneoplastic antibodies that interact with the cytoplasmatic antigens of a subpopulation of oligodendrocytes. They are usually associated with the presence of a small cell carcinoma. We report the case of a patient with an epidermoid carcinoma of the lung and paraneoplastic cerebellous ataxia associated with anti CV2 antibodies. CASE REPORT: Male aged 73, ex smoker for 10 years, with a 45 packet/year habit. He presented a 5 month old constitutional syndrome. Altered gait with a sensation of instability. During the course of the exploration, we detected an increase in the support base, the impossibility to walk in tandem, non exhaustible horizontal nystagmus in bilateral extreme look, and vertical when looking down, with abolition of Achilles reflexes. Brain MR revealed supratentorial demyelinating lesions of a probable ischemic origin. Anti CV 2 antibodies in serum positive (anti HU negative). Biopsy performed using bronchial brushing in the left upper lobe detected the presence of malign epithelial strain, not microcytic, cells, which are compatible with epidermoid carcinoma. DISCUSSION: Anti CV2 antibodies have only been found in patients who have developed a neurological syndrome within the context of a neoplasia. The detection of these antibodies in serum is related with the presence of a concealed neoplasia

[Type 8 spinocerebellar ataxia. A report of a family]. / Ataxia espinocerebelosa tipo 8. Descripción de una familia.

INTRODUCTION: Over the past decade, from the genetic point of view, several of the entities included in the group of hereditary ataxias have been identified. We report a Spanish family with type 8 spinocerebellar ataxia (SCA8), one of the most recent hereditary ataxias to be described from the clinical and genetic points of view. CLINICAL CASE: A 59 year old woman consulted us complaining of progressive dysarthria and unsteady gait. The only abnormal findings on neurological examination were those of cerebellar involvement. The patient s mother had a similar condition, characterized by difficulty in speaking which started when she was 62 years old and progressed to anarthria. Cranial magnetic resonance showed the presence of cerebellar atrophy with no signs of atrophy of the brainstem. On electromyographic studies there were no signs of neuropathy. Visual, auditory and sensory evoked potentials were normal. Genetic studies showed expansion of trinucleotide CTG (112 repetitions in the expanded allele and 28 repetitions in the normal allele) on the gene responsible for SCA8. CONCLUSION: SCA8 should be included in the differential diagnosis of progressive cerebellar syndromes, especially when changes in speech predominate with regard to other cerebellar signs.

[Cerebral infarct as a presentation of a hereditary defect of type II C protein]. / Infarto cerebral como forma de presentación de un déficit hereditario de proteína C tipo II.

The case of a 50 year-old patient with a cerebral infarct related to a deficit in type II C protein is described. The patient showed no other vascular risk factor and the cardiological study, which included a transthoracic and a transoesophagic echogram ruled out the presence of embologenic cardiopathy. A family study detected the presence of a deficit of C protein in 6 of the 8 sons and in the patient's sister who had a deep vein thrombosis at the age of 54. A hereditary deficiency in C protein was confirmed. We consider it necessary to perform hypercoagulability studies which include the determination of C protein in patients under 55 years of age with cerebral infarcts of unknown cause, especially when there is a family history of thrombosis.

[A reversible posterior leukoencephalopathy syndrome]. / Síndrome de leucoencefalopatía posterior reversible.

INTRODUCTION AND METHOD: The reversible posterior leukoencephalopathy (RPLS) was initially described by Hinchey et al in patients hospitalized due to different acute process that cause hypertension and renal disease that were being treated with immunosuppressive agents. Clinically it produces an acute or subacute encephalopathy that usually agrees with a fast increase of blood pressure. Neuroimaging technique demonstrated abnormalities involving the white matter, especially bilateral edema in the posterior portions of the cerebral hemispheres, although it can also affect to any other cerebral area, trunk or cerebellum. The production mechanism is not well know. In case of hypertensive encephalopathy and eclampsia of pregnancy it is believed to be caused by vascular and endothelial autoregulation alterations, and when it's related to immunosuppressors the edema seems to have a cytotoxical origin. The particularity that defines the RPLS is that, in most cases, neurological symptoms and white matter lesions disappear after anti hypertensive treatment or when immunosuppressive agents is ceased. CONCLUSION: The RPLS is an uncommon neurological complication, however each time more news cases appear in the medical literature. The excellent evolution and treatment response that these patients show and the full clinical and radiological recuperation suggest the need of its early identification to avoid unnecessary diagnostic studies or wrong treatments.

[Amaurosis fugax as the sole manifestation of a dural arteriovenous fistula]. / Amaurosis fugaz como única manifestación de una fístula arteriovenosa dural.

INTRODUCTION: Ophthalmologic disorders caused by arteriovenous malformations (AVM) are generally related with alterations in the cavernous sinus or papilloedema. However, the appearance of amaurosis fugax (AF) as the sole clinical manifestation of an AVM has very rarely been reported in the literature. CASE REPORT: We present the case of a 64 year old male patient who displayed recurring episodes of temporary monocular blindness (AF) as a consequence of the haemodynamic disorders triggered off in the course of a dural AVM. DISCUSSION: The arteriovenous fistula, located in the anterior fossa, gives rise to theft phenomena in the region of the arteries that nourish the retina and trigger episodes of AF of an essentially haemodynamic nature.

[Clinical and neuroimaging findings in a family with CADASIL associated to C475T mutation]. / Hallazgos clínicos y de neuroimagen en una familia con CADASIL asociada a la mutación C475T.

INTRODUCTION: The term CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) refers to an autosomal dominant hereditary arteriopathy of the brain that is characterised by headache, recurring strokes and progressive cognitive deterioration. We report the case of another family with CADASIL and emphasise the importance of a genetic study in its diagnosis. CASE REPORT: A 62-year-old female patient with repeating lacunar strokes, subcortical dementia and a family history of dementia and strokes. Neuroimaging studies conducted on the patient and her siblings showed signs of leukoencephalopathy and lacunar infarctions. The ultrastructural study of the biopsy performed on a sample of the patient's skin, which included five dermal vessels, did not show any electron-dense deposits. The genetic study revealed the presence of mutation C475T in exon 4 of NOTCH3. CONCLUSIONS: The possible presence of CADASIL must be suspected in patients with symptoms of cerebrovascular disease or dementia who present characteristic alterations in the magnetic resonance brain scan, especially when there is a compatible family history. The first choice diagnostic procedure must be a genetic study.