Guía de tratamiento del deterioro de la marcha con fampridina de liberación prolongada (Fampyra (R)) en pacientes con esclerosis múltiple / A guide to treating gait impairment with prolonged-release fampridine (Fampyra(R)) in patients with multiple sclerosis

INTRODUCCIÓN: La alteración de la marcha es frecuente en la esclerosis múltiple (EM) y tiene un gran impacto negativo en los pacientes pues conlleva a la pérdida progresiva de autonomía personal y social, y de productividad laboral. Esta guía pretende establecer recomendaciones para la evaluación del deterioro de la marcha y el uso de fampridina de liberación prolongada (fampridina-LP) como tratamiento de pacientes con EM y deterioro de la marcha en España. DESARROLLO: Fampridina-LP a dosis de 10 mg cada 12 h es actualmente el único fármaco autorizado para mejorar el trastorno de la marcha en adultos con EM. En la práctica clínica, el fármaco ha demostrado además que mejora de forma significativa la calidad de vida de los pacientes que responden al tratamiento. La respuesta se puede evaluar mediante la prueba cronometrada de la marcha de 25 pies (T25FW) o el cuestionario MSWS-12 que deben realizarse antes y después del inicio del tratamiento. El tiempo mínimo recomendado para evaluar la respuesta inicial es de 2 semanas. Para considerar a un paciente como respondedor y continuar el tratamiento debe presentar, según indica la ficha técnica, una disminución en el tiempo T25FW o mejoría en el MSWS-12. Se recomienda realizar las revaluaciones al menos cada 6 meses. En los casos en que se considere la valoración de la calidad de vida, se recomienda la utilización del cuestionario de salud Short Form-36 (SF-36) o la escala MS Impact Scale-29 (MSIS-29). Es un fármaco en general bien tolerado y con buen perfil de seguridad. Se recomienda su administración en ayunas y control periódico de la función renal. CONCLUSIONES: Estas recomendaciones permiten garantizar una prescripción eficiente y más segura, y ayudan al manejo de fampridina-LP como tratamiento del deterioro de la marcha en pacientes adultos con EM en España

INTRODUCTION: Gait impairment, a frequent sign in multiple sclerosis (MS), places a major burden on patients since it results in progressive loss of personal and social autonomy, along with work productivity. This guide aims to provide recommendations on how to evaluate gait impairment and use prolonged-release fampridine (PR-fampridine) as treatment for MS patients with gait impairment in Spain. DEVELOPMENT: PR-fampridine dosed at 10 mg every 12hours is currently the only drug approved to treat gait impairment in adults with MS. Additionally, PR-fampridine has been shown in clinical practice to significantly improve quality of life (QoL) in patients who respond to treatment. Treatment response can be assessed with the Timed 25-Foot Walk (T25FW) or the 12-item MS Walking Scale (MSWS-12); tests should be completed before and after starting treatment. The minimum time recommended for evaluating treatment response is 2 weeks after treatment onset. Patients are considered responders and permitted to continue the treatment when they demonstrate a decrease in their T25FW time or an increase in MSWS-12 scores. A re-evaluation is recommended at least every 6 months. The SF-36 (Short Form-36) and the MSIS-29 (MS Impact Scale-29) tests are recommended for clinicians interested in performing a detailed QoL assessment. This drug is generally well-tolerated and has a good safety profile. It should be taken on an empty stomach and renal function must be monitored regularly. CONCLUSIONS: These recommendations will help ensure safer and more efficient prescription practices and easier management of PR-fampridine as treatment for gait impairment in Spanish adults with MS

A guide to treating gait impairment with prolonged-release fampridine (Fampyra®) in patients with multiple sclerosis. / Guía de tratamiento del deterioro de la marcha con fampridina de liberación prolongada (Fampyra®) en pacientes con esclerosis múltiple.

INTRODUCTION: Gait impairment, a frequent sign in multiple sclerosis (MS), places a major burden on patients since it results in progressive loss of personal and social autonomy, along with work productivity. This guide aims to provide recommendations on how to evaluate gait impairment and use prolonged-release fampridine (PR-fampridine) as treatment for MS patients with gait impairment in Spain. DEVELOPMENT: PR-fampridine dosed at 10mg every 12hours is currently the only drug approved to treat gait impairment in adults with MS. Additionally, PR-fampridine has been shown in clinical practice to significantly improve quality of life (QoL) in patients who respond to treatment. Treatment response can be assessed with the Timed 25-Foot Walk (T25FW) or the 12-item MS Walking Scale (MSWS-12); tests should be completed before and after starting treatment. The minimum time recommended for evaluating treatment response is 2 weeks after treatment onset. Patients are considered responders and permitted to continue the treatment when they demonstrate a decrease in their T25FW time or an increase in MSWS-12 scores. A re-evaluation is recommended at least every 6 months. The SF-36 (Short Form-36) and the MSIS-29 (MS Impact Scale-29) tests are recommended for clinicians interested in performing a detailed QoL assessment. This drug is generally well-tolerated and has a good safety profile. It should be taken on an empty stomach and renal function must be monitored regularly. CONCLUSIONS: These recommendations will help ensure safer and more efficient prescription practices and easier management of PR-fampridine as treatment for gait impairment in Spanish adults with MS.

[Efficacy of group reminiscence therapy for people with dementia. Systematic literature review and meta-analysis]. / Eficacia de la terapia de reminiscencia grupal en personas con demencia. Revision sistematica y metaanalisis.

INTRODUCTION: Reminiscence therapy is one of the most effective psychosocial interventions for people with dementia. AIMS: To analyse the effectiveness of group reminiscence therapy in people with dementia and to check their involvement in the design and evaluation of the interventions. PATIENTS AND METHODS: CINHAL, PubMed, Psicodoc and PsycINFO databases were searched for the period of 2004 to 2016. A systematic search was performed, as well as a quality assessment and a meta-analysis of the articles. RESULTS: The 14 studies selected had a moderate risk of bias. People with dementia who received group reminiscence therapy experienced an improvement in cognition (dMR = 0.26; 95% CI: 0.11-0.40; p = 0.0006; I2 = 0%) which was larger than the one observed in the control group (dc = 0.37; 95% CI: 0.11-0.63; p = 0.005; I2 = 0%). There was no improvement in mood, quality of life, behaviour or activities of daily living. People with dementia were not included in the design nor in the evaluation of the interventions. CONCLUSIONS: Group reminiscence therapy for people with dementia has favourable effects in cognition. There is a need for the inclusion of people with dementia in the design and planning of the interventions and for more randomised controlled trials.

TITLE: Eficacia de la terapia de reminiscencia grupal en personas con demencia. Revision sistematica y metaanalisis.Introduccion. La terapia de reminiscencia es una de las intervenciones psicosociales mas eficaces para personas con demencia. Objetivos. Analizar la eficacia de la terapia de reminiscencia grupal en personas con demencia y comprobar su participacion en el diseño y evaluacion. Pacientes y metodos. Se revisaron las bases de datos CINHAL, PubMed, Psicodoc y PsycINFO, en el periodo 2004-2016, y se realizo una revision sistematica, evaluacion de calidad y metaanalisis de los articulos. Resultados. Los 14 estudios seleccionados presentaron riesgo de sesgo moderado, los participantes que recibieron terapia de reminiscencia experimentaron una mejoria leve en cognicion (dMR = 0,26; IC 95%: 0,11-0,40; p = 0,0006; I2 = 0%), y esta fue mayor que la del grupo control (dc = 0,37; IC 95%: 0,11-0,63; p = 0,005; I2 = 0%). No se encontraron mejorias en el estado de animo, la calidad de vida, las alteraciones de conducta ni las actividades de la vida diaria. Ningun estudio incluyo a las personas con demencia ni a sus acompañantes en el diseño y evaluacion. Conclusiones. La terapia de reminiscencia grupal tiene efectos favorables sobre la cognicion. Es necesaria la inclusion de las personas con demencia en el diseño y planificacion de las intervenciones, asi como la realizacion de mas ensayos clinicos aleatorizados.

Consenso español actualizado sobre el uso del natalizumab (Tysabri(R))-2013 / Spanish consensus on the use of natalizumab (Tysabri (R))-2013

Introducción: Natalizumab es un tratamiento que ha demostrado ser muy eficaz en los ensayos clínicos y muy efectivo en la práctica clínica en los pacientes con esclerosis múltiple recurrente-remitente, en cuanto a la reducción del número de brotes, enlentecimiento de la progresión de la enfermedad y variables de resonancia magnética. Sin embargo, el fármaco se ha asociado con el riesgo de desarrollar leucoencefalopatía multifocal progresiva (LMP). Los nuevos datos aparecidos sobre la monitorización de los pacientes en tratamiento, el diagnóstico, y manejo de la LMP y otros temas de interés como la actuación ante la suspensión del natalizumab se han incorporado en esta actualización del primer consenso sobre el uso del natalizumab publicado en el 2011. Material y métodos: En esta actualización se procedió con la misma metodología que la del primer consenso. Un grupo de expertos españoles en esclerosis múltiple (los autores de esta actualización) revisaron toda la bibliografía disponible sobre natalizumab hasta la fecha, y basándose en su experiencia clínica definieron los temas relevantes a actualizar. Un primer borrador se sometió a ciclos de revisión hasta llegar a la versión final. Resultados y conclusiones: Los estudios de práctica clínica han demostrado que el cambio a natalizumab es más efectivo que el cambio entre inmunomoduladores, y apoyan una mayor conveniencia del tratamiento temprano con natalizumab frente a una utilización más tardía como terapia de rescate. A pesar de ser un fármaco muy eficaz, se deben tener en cuenta los posibles efectos adversos y, en particular, la probabilidad de desarrollar LMP. El neurólogo debe explicar al paciente en detalle los riesgos y beneficios del tratamiento frente al riesgo de la esclerosis múltiple usando términos comprensibles. Antes de empezar el tratamiento, deben estar disponibles las pruebas de laboratorio y las imágenes de resonancia magnética que permitan hacer un seguimiento adecuado. El riesgo de LMP debe estratificarse en alto, medio y bajo de acuerdo con la presencia o ausencia de anticuerpos frente al virus JC, antecedente de tratamiento inmunosupresor y duración del tratamiento. La presencia de anticuerpos antivirus JC, aunque significativa, no se puede tomar como una contraindicación absoluta para el natalizumab. La presente actualización establece unas recomendaciones generales, pero los neurólogos deben aplicar su experiencia clínica para hacer un seguimiento individualizado de los pacientes

Introduction: Natalizumab treatment has been shown to be very efficacious in clinical trials and very effective in clinical practice in patients with relapsing-remitting multiple sclerosis, by reducing relapses, slowing disease progression, and improving magnetic resonance imaging patterns. However, the drug has also been associated with a risk of progressive multifocal leukoencephalopathy (PML). The first consensus statement on natalizumab use, published in 2011, has been updated to include new data on diagnostic procedures, monitoring for patients undergoing treatment, PML management, and other topics of interest including the management of patients discontinuing natalizumab. Material and methods: This updated version followed the method used in the first consensus. A group of Spanish experts in multiple sclerosis (the authors of the present document) reviewed all currently available literature on natalizumab and identified the relevant topics would need updating based on their clinical experience. The initial draft passed through review cycles until the final version was completed. Results and conclusions: Studies in clinical practice have demonstrated that changing to natalizumab is more effective than switching between immunomodulators. They favour early treatment with natalizumab rather than using natalizumab in a later stage as a rescue therapy. Although the drug is very effective, its potential adverse effects need to be considered, with particular attention to the patient's likelihood of developing PML. The neurologist should carefully explain the risks and benefits of the treatment, comparing them to the risks of multiple sclerosis in terms the patient can understand. Before treatment is started, laboratory tests and magnetic resonance images should be available to permit proper follow-up. The risk of PML should be stratified as high, medium, or low according to presence or absence of anti-JC virus antibodies, history of immunosuppressive therapy, and treatment duration. Although the presence of anti-JC virus antibodies is a significant finding, it should not be considered an absolute contraindication for natalizumab. This update provides general recommendations, but neurologists must use their clinical expertise to provide personalised follow-up for each patient

Assessment of the reproducibility of oligoclonal IgM band detection for its application in daily clinical practice.

BACKGROUND: The presence of oligoclonal IgM bands (OCMB) in cerebrospinal fluid (CSF) is an unfavourable prognostic marker in multiple sclerosis. There is no commercial test to investigate OCMB status. However, a sensitive and specific isoelectrofocusing (IEF) and western blot method was described. We aimed to study the inter-centre reproducibility of this technique, a necessary condition for a reliable test to be incorporated into clinical practice. METHODS: The presence of OCMB was analysed by IEF and western blot with prior reduction of pentameric IgM. We assayed the reproducibility of this test in a blinded multicentre study performed in 13 university hospitals. Paired-CSF and serum samples from 52 neurological patients were assayed at every centre. RESULTS: Global analysis rendered a concordance of 89.8% with a kappa value of 0.71. CONCLUSION: These data indicate that OCMB detection by means of IEF and western blot with IgM reduction shows a good interlaboratory reproducibility and thus can be used in daily clinical setting.

Spanish consensus on the use of natalizumab (Tysabri®)-2013.

INTRODUCTION: Natalizumab treatment has been shown to be very efficacious in clinical trials and very effective in clinical practice in patients with relapsing-remitting multiple sclerosis, by reducing relapses, slowing disease progression, and improving magnetic resonance imaging patterns. However, the drug has also been associated with a risk of progressive multifocal leukoencephalopathy (PML). The first consensus statement on natalizumab use, published in 2011, has been updated to include new data on diagnostic procedures, monitoring for patients undergoing treatment, PML management, and other topics of interest including the management of patients discontinuing natalizumab. MATERIAL AND METHODS: This updated version followed the method used in the first consensus. A group of Spanish experts in multiple sclerosis (the authors of the present document) reviewed all currently available literature on natalizumab and identified the relevant topics would need updating based on their clinical experience. The initial draft passed through review cycles until the final version was completed. RESULTS AND CONCLUSIONS: Studies in clinical practice have demonstrated that changing to natalizumab is more effective than switching between immunomodulators. They favour early treatment with natalizumab rather than using natalizumab in a later stage as a rescue therapy. Although the drug is very effective, its potential adverse effects need to be considered, with particular attention to the patient's likelihood of developing PML. The neurologist should carefully explain the risks and benefits of the treatment, comparing them to the risks of multiple sclerosis in terms the patient can understand. Before treatment is started, laboratory tests and magnetic resonance images should be available to permit proper follow-up. The risk of PML should be stratified as high, medium, or low according to presence or absence of anti-JC virus antibodies, history of immunosuppressive therapy, and treatment duration. Although the presence of anti-JC virus antibodies is a significant finding, it should not be considered an absolute contraindication for natalizumab. This update provides general recommendations, but neurologists must use their clinical expertise to provide personalised follow-up for each patient.

Eficacia de los tratamientos de fisioterapia para el dolor lumbar en niños y adolescentes. Revisión sistemática / No disponible

El dolor lumbar es uno de los principales motivos para la utilización de la asistencia sanitaria, y es un problema de salud frecuente en niños y adolescentes. Varios autores han evidenciado que tener dolor lumbar en la infancia aumenta el riesgo de sufrirlo de adulto. El objetivo de este trabajo es revisar la evidencia empírica de los tratamientos de fisioterapia para el dolor lumbar en niños y adolescentes, estimar su eficacia y analizar la calidad metodológica de los estudios. Se consultaron estudios experimentales en las bases de datos Cochrane, ISI Web of Knowledge, Medline, PEDro y LILACS; revistas electrónicas especializadas y otros procedimientos. Ocho artículos se incluyeron en la revisión sistemática, que dio lugar a 16 estudios independientes (11 grupos tratados y 5 grupos controles). Los 8 artículos seleccionados incluyeron tratamientos con educación de la espalda, ejercicio, terapia manual y acondicionamiento físico terapéutico. El tratamiento con ejercicio es el más utilizado por los autores. Se concluye que los tratamientos de fisioterapia son eficaces para el dolor lumbar en niños y adolescentes. Finalmente, la calidad de los estudios futuros debe mejorar mediante procedimientos más eficaces de enmascaramiento, utilización de grupos de control y realizar análisis de fiabilidad de los instrumentos de evaluación (AU)

Low back pain is one of the main reasons for the use of health care, and is a common health problem in children and adolescents. Several authors have shown that having low back pain in childhood increases the risk for adult. The aim of the present study is to review the empirical evidence regarding physiotherapy treatments for low back pain in children and adolescents, assess their effectiveness, and to analyze the methodological quality of the papers. Experimental studies were consulted in the electronic databases Cochrane, ISI Web of Knowledge, Medline, PEDro and LILACS; specialized electronic journals and other procedures. 8 articles were included in the systematic review, which resulted in 16 independent studies (11 treatment groups and 5 control groups). The 8 articles selected include treatments with back education, exercise, manual therapy and therapeutic physical conditioning. Treatment with exercise is the most frequently used by authors. We conclude that physiotherapy treatments are effective for low back pain in children and adolescents. Finally, the quality of future studies should be improved through more effective masking procedures, use of control groups and analysis of reliability of assessment instruments (AU)

Eficacia de los tratamientos de fisioterapia preventivos para el cuidado de la espalda en niños y adolescentes. Revisión sistemática / Efficacy of preventive physiotherapy treatments for back care in children and adolescents. A systematic review

Objetivo Conocer los tratamientos fisioterapéuticos preventivos más eficaces para el cuidado de la espalda en niños y adolescentes y analizar la calidad metodológica de los artículos. Estrategia de búsqueda Se llevo a cabo una revisión sistemática de ensayos controlados en las bases de datos de Cochrane, MEDLINE, PEDro, Web of Science e IME. Selección de estudios y datos Se incluyeron un total de 16 trabajos que cumplieron con los criterios de selección, dando lugar a 19 estudios independientes. Síntesis de resultados Los 19 estudios analizados incluyeron tratamientos con higiene postural de forma aislada, tratamientos combinados de higiene postural y ejercicios fisioterapéuticos e higiene postural y actividad física. Conclusiones El tratamiento de higiene postural es el más utilizado por los autores. El tratamiento combinado de higiene postural con ejercicio fisioterapéutico es eficaz para la adquisición de conocimientos y conductas. La calidad metodológica de los estudios se relaciona con la eficacia del tratamiento (AU)

Objective To identify the most effective preventive physiotherapy treatments for back care in children and adolescents and to analyze the methodological quality of the articles. Search strategy A systematic review of controlled trials was conducted in the Cochrane, MEDLINE, PEDro, Web of Science and IME databases. Selection of studies A total de 16 research papers that fulfilled the selection criteria were included, producing 19 independent studies. Results The 19 studies analyzed included treatments with postural hygiene applied independently, combined treatments of postural hygiene and physical therapy exercises and postural hygiene and physical activity. Conclusions Treatment of hygiene postural is that used most frequently by the authors. Combined treatment of postural hygiene and physical therapy exercises is effective for the acquisition of knowledge and behaviors. The methodological quality of the studies is related to the effectiveness of the treatment (AU)

[Bone marrow stem cell transplantation in amyotrophic lateral sclerosis: technical aspects and preliminary results from a clinical trial]. / Terapia celular para la esclerosis lateral amiotrófica: aspectos técnicos y resultados preliminares del estudio CMN/ELA.

Patients with amyotrophic lateral sclerosis (ALS) experience progressive and irreversible paralysis as a result of the continued loss of motor neurons, which leads to death in less than five years. To date, there is no treatment that can change the progression of this disease. Bone marrow stem cells have shown neural regenerative and neural repairing properties. Specifically, our group showed in a murine model of the disease that these cells, when injected in the spinal cord, can rescue motor neurons through the secretion of GDNF. Based on these results, we designed a phase I/II clinical trial for the purpose of demonstrating the viability of the intraspinal injection of autologous bone marrow mononuclear cells in patients with bulbar onset ALS, with an evolution between 6 and 36 months, with a forced vital capacity (FVC) 50% and T90 29%. This article describes the technique for extracting 60 mL of bone marrow used for the intervention, processing it by density gradient, and the neurosurgical technique used for implanting it. After 6 months of follow-up, the few adverse events reported in the first seven patients included seem to show that the procedure is safe and viable. Most of these patients, including two with a rapid deterioration, have stabilized the progression of their FVC and the neurologic scales measured. The data obtained so for seem to justify the design of new trials more oriented toward the efficacy of the procedure.

Generalización de la fiabilidad: un enfoque metaanalítico aplicado a la fiabilidad / Reliability generalization: A meta-analytic approach to reliability coefficients

La fiabilidad no es una propiedad inherente al test, por lo que frases del tipo “la fiabilidad del test es de 0,80” son incorrectas. Ello se debe a que la fiabilidad es una propiedad de las puntuaciones obtenidas por un test en una aplicación concreta de éste. La generalización de la fiabilidad (GF) es un nuevo tipo de metaanálisis que permite examinar empíricamente la variabilidad de las estimaciones de la fiabilidad en diferentes aplicaciones de un test. Los estudios de GF están poniendo en evidencia lo inadecuado que resulta esa práctica habitual de los investigadores de inducir la fiabilidad a partir de estimaciones previas de ésta. En este artículo se presenta una panorámica del enfoque de GF, describiendo cuáles son sus fases de realización. Además, se discuten algunos de los problemas estadísticos más importantes de los estudios GF, tales como: a) procedimientos de transformación de los coeficientes de fiabilidad; b) métodos de ponderación de los coeficientes, y c) modelos estadísticos asumibles (AU)

Reliability is not a property inherent to the test, so that sentences such as “the test reliability is 0.80” are wrong. That is because reliability is a property of scores obtained in a given application o a test. Reliability generalization (RG) is a new kind of meta-analysis which enables to empirically examine the variability of the reliability estimates across different applications of a test. The RG studies are evidencing how unadvisable is the usual practice of researchers of inducing reliability from previous estimates. In this article an overview of the RG approach is presented, describing the required steps. Moreover, some of the most important statistical issues concerning RG studies are discussed, such as: (a) transforming procedures of the reliability coefficients, (b) weighting methods of the coefficients, and (c) statistical models that can be assumed (AU)

El metaanálisis en el ámbito de las Ciencias de la Salud: una metodología imprescindible para la eficiente acumulación del conocimiento / Meta-analysis in the Health Sciences: an indispensable methodology for the efficient accumulation of knowledge

El metaanálisis es una metodología para la revisión sistemática y cuantitativa de la investigación, ampliamente consolidada y aplicada en las Ciencias de la Salud. Ofrece las técnicas necesarias para acumular rigurosa y eficientemente los resultados cuantitativos de los estudios empíricos sobre un mismo problema de salud, permitiendo a los profesionales de la salud la adopción de decisiones bien informadas en sus respectivas áreas de trabajo. Con la ayuda de algunos ejemplos tomados del ámbito de la Fisioterapia, en este artículo describimos las principales características del metaanálisis, sus fases de ejecución y su utilidad en la investigación sanitaria. Finalmente, se muestran la relevancia del metaanálisis dentro del enfoque de la medicina basada en la evidencia y algunas perspectivas de futuro del metaanálisis(AU)

Meta-analysis is a methodology for the systematic and quantitative review of research that is widely consolidated and applied in Health Sciences. It offers the necessary techniques to rigorously and efficiently accumulate quantitative results on the empirical studies regarding a common health problem. It allows health care professionals to make well-informed decisions in their respective areas. In this article and with the help of some examples obtained from within the physiotherapy setting, we have described the main characteristics of meta-analysis, its execution phases and its usefulness in health care research. The relevance of meta-analysis in the evidence based medicine approach and some perspectives on the future of meta-analysis are shown(AU)

Averaging dependent effect sizes in meta-analysis: a cautionary note about procedures.

When a primary study includes several indicators of the same construct, the usual strategy to meta-analytically integrate the multiple effect sizes is to average them within the study. In this paper, the numerical and conceptual differences among three procedures for averaging dependent effect sizes are shown. The procedures are the simple arithmetic mean, the Hedges and Olkin (1985) procedure, and the Rosenthal and Rubin (1986) procedure. Whereas the simple arithmetic mean ignores the dependence among effect sizes, both the procedures by Hedges and Olkin and Rosenthal and Rubin take into account the correlational structure of the effect sizes, although in a different way. Rosenthal and Rubin's procedure provides the effect size for a single composite variable made up of the multiple effect sizes, whereas Hedges and Olkin's procedure presents an effect size estimate of the standard variable. The three procedures were applied to 54 conditions, where the magnitude and homogeneity of both effect sizes and correlation matrix among effect sizes were manipulated. Rosenthal and Rubin's procedure showed the highest estimates, followed by the simple mean, and the Hedges and Olkin procedure, this last having the lowest estimates. These differences are not trivial in a meta-analysis, where the aims must guide the selection of one of the procedures.

[Neurological manifestations of Paget's disease: presentation of one case and review of the literature]. / Manifestaciones neurológicas en la enfermedad de Paget: presentación de un caso y revisión de la literatura.

INTRODUCTION: Paget's disease is a frequent metabolic disease. It is usually diagnosed as a accidental finding. Initial symptoms usually consist of generalized pain in bones. When it affects the Central Nervous System, symptoms usually appear in advanced cases and are due mainly to compression of the spinal cord. Neurological problems as the first manifestation of the disease are exceptionally found. CLINICAL CASE: We report the case of a woman affected by Paget's disease who presented as a triventricular obstructive hydrocephalus. The patient was 72 years old and consulted first to the emergency ward due to headache, gait disorders and cognitive abnormalities. COMMENTS: The most remarkable data about this patient are the indolent course of the disease which caused its debut as hydrocephalus associated to basilar impression, its favourable evolution after ventricular drainage and the almost absolute absence of previous similar cases reported in literature all over the last years.

[Stiff-man syndrome. Presentation of a new case]. / Síndrome de la persona rígida. Presentación de un nuevo caso.

INTRODUCTION: The stiff-man syndrome (SPR) is a rare neurological condition characterized by the presence of marked, involuntary rigidity of the axial muscles and limbs, together with intense painful muscle spasms which characteristically occur following external stimuli such as sudden noises, brusque movements or emotional stimuli. Symptoms are markedly improved by sleep and by diazepam. The aetiology is unknown, although it is associated with certain auto-immune disorders, particularly diabetes mellitus (DM) and others such as thyroid disease, vitiligo, pernicious anaemia, adrenal insufficiency, etc. The presence of high titres of glutamate-decarboxylase (GAD) antibodies seems to indicate an auto-immune aetiology. CLINICAL CASE: We describe a 59 year old woman who complained of an illness starting seven years previously with progressive pain and contractions of the dorso-lumbar muscles, which later spread to the cervical and abdominal muscles and to the upper limbs. From the time of onset, there were exacerbations of the condition following external stimuli. Also there was generalized vitiligo and whilst this progressed, DM developed (which finally required insulin to control it). On EMG there was continuous muscular activity and absence of muscle relaxation. The presence of high titres of anti-nuclear antibodies, gastric parietal cell antibodies and anti-GAD was very marked. There was a spectacular response to treatment with diazepam, with progressive improvement although ever increasing dosage was required. CONCLUSIONS: A new case of the 'stiff-man' syndrome is presented and aspects of aetiopathology and treatment are reviewed.

[Delayed diagnosis of phenylketonuria as the cause of mental retardation in an adolescent]. / Diagnóstico tardío de fenilcetonuria como causa de retraso mental en un adolescente.

INTRODUCTION: The hyperphenylalaninemias (HFA) form a diverse group of recessive autosomic disorders. They are caused by defects in the hepatic system for hydroxylation of the amino acid phenylalamine to tyrosine. The estimated incidence is approximately 10 cases per 100,000 live births. Children with this metabolic disorder may present with varied neurological symptoms. Control of plasma levels, so that they are more normal as soon as possible after birth, significantly prevents mental retardation and other neuropsychological dysfunction. For this reason HFA has been included in neonatal screening. However, some patients are not detected on screening. When they are adults, these patients pose problems of diagnosis for neurologists who attend adults. CLINICAL CASE: We describe an adolescent with mental and linguistic retardation, in whom neonatal screening to rule out metabolic defects was normal. At the age of 15, the phenylalanine in blood and urine were found to be raised. On cerebral magnetic resonance changes typical of pheynylketonuria (PKU) were seen. CONCLUSIONS: The HFA should be considered as causes of cerebral dysfunction in adults, since in spite of neonatal screening, false negatives may occur. We describe a clinical case and consider different forms of hyperphenylaleninemias. Their diagnosis and treatment.