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

AIM: To evaluate the effectiveness and safety of fingolimod in clinical practice in Navarra, Gipuzkoa and La Rioja regions. PATIENTS AND METHODS: We conducted a retrospective multi-centre study with recurrent multiple sclerosis patients treated with fingolimod, following the product data sheet. The following data were evaluated: annualised relapse rate (ARR), percentage of patients free from relapses, disability using the Expanded Disability Status Scale (EDSS) and the percentage of patients without gadolinium-enhancing lesions. RESULTS: A total of 113 patients were treated with fingolimod: 6% were naive, and 58% and 35% were patients previously treated with an immunomodulator and natalizumab, respectively. Fingolimod lowered the ARR after the first (67%; 1 to 0.3; p < 0.0001) and second (89%; 1 to 0.1; p < 0.0001) years of treatment, and thus the number of patients free from relapses during the treatment increased. The baseline EDSS was 3 and after treatment with fingolimod was 2.5 in both years. The percentage of patients without gadolinium-enhancing lesions after the first year of treatment was 77%. Similar results were observed in naive patients and in those previously treated with an immunomodulator. In patients previously treated with natalizumab no changes were observed following the treatment. CONCLUSIONS: The use of fingolimod in clinical practice showed an effectiveness similar to that observed in clinical trials. There were no changes in the ARR after changing from natalizumab, and only one patient presented a 'relapse' after withdrawal of natalizumab. Fingolimod acts like a safe drug, with scarce side effects and a low percentage of drop-outs.

TITLE: Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Navarra, Gipuzkoa y La Rioja.Objetivo. Evaluar la efectividad y seguridad del fingolimod en la practica clinica en las regiones de Navarra, Gipuzkoa y La Rioja. Pacientes y metodos. Estudio retrospectivo y multicentrico de pacientes con esclerosis multiple recurrente tratados con fingolimod, siguiendo la ficha tecnica. Se evaluo la tasa anualizada de brotes (TAB), el porcentaje de pacientes libres de brotes, la discapacidad usando la escala expandida del estado de discapacidad (EDSS) y el porcentaje de pacientes sin lesiones captantes de gadolinio. Resultados. Un total de 113 pacientes fueron tratados con fingolimod: el 6%, naive, y el 58% y 35%, pacientes tratados previamente con inmunomodulador y natalizumab, respectivamente. El fingolimod disminuyo la TAB tras el primer (67%; 1 a 0,3; p < 0,0001) y segundo (89%; 1 a 0,1; p < 0,0001) año de tratamiento, y aumento asi el porcentaje de pacientes libres de brotes durante el tratamiento. La EDSS basal fue 3 y despues del tratamiento con fingolimod fue 2,5 en ambos años. El porcentaje de pacientes sin lesiones captantes de gadolinio tras el primer año de tratamiento fue del 77%. Resultados similares se observaron en los pacientes naive y en los tratados previamente con inmunomodulador. En los pacientes tratados previamente con natalizumab no se observaron cambios tras el tratamiento. Conclusiones. El uso del fingolimod en la practica clinica mostro una efectividad similar a la eficacia observada en ensayos clinicos. No hubo cambios en la TAB al cambiar desde natalizumab, y solo un paciente tras suspender el natalizumab presento 'rebrote'. El fingolimod se comporta como un farmaco seguro, con escasos efectos adversos y con un bajo porcentaje de abandonos.

Cortico-juxtacortical involvement increases risk of epileptic seizures in multiple sclerosis.

OBJECTIVES: Previous studies have reported an increased risk for epileptic seizures in multiple sclerosis (MS) patients. However, data on the pathogenesis of seizures remain inconclusive. The aim of our study is to evaluate prevalence, clinical and paraclinical features of epileptic attacks in our MS cohort and to search MS-specific risk factors for epileptic seizures. MATERIALS AND METHODS: In this cohort of 428 MS patients, 13 patients were identified with epileptic seizures occurring at any point during the course of MS including at MS onset. As a control group, we selected 26 MS patients without seizures and matched for gender, age and date of MS onset. We compared demographic features and clinic-radiological findings between the both groups. RESULTS: Thirteen patients (3%) were identified as having epileptic attacks. Ten patients (77%) experienced focal seizures, half of whom had confirmed secondary generalization. We did not find an association between seizures and disease course. Most patients had a single or few (2-5) seizures. MS patients with seizures had a significantly higher number of cortical and juxtacortical lesions on T2-weighted/fluid attenuation inversion recovery magnetic resonance imaging than control group [OR = 2.6 CI95% (1.0-6.5); P = 0.047]. CONCLUSIONS: Our findings support a credible role of cortical and juxtacortical involvement in the development of epileptic seizures in MS.

Neuritis óptica inflamatoria / Inflammatory optic neuritis

La neuritis óptica inflamatoria (NO) es la causa másfrecuente de pérdida visual aguda en adultos jóvenes.Aunque el pronóstico visual es excelente en la mayoríade los casos, muchos pacientes desarrollarán otra patologíacomo esclerosis múltiple en la evolución posterior.La historia natural de la NO ha sido estudiada enmúltiples trabajos en los últimos años; uno de los másimportantes es el Optic Neuritis Treatment Trial.La Resonancia Magnética tiene un papel fundamentalen el diagnóstico etiológico de la NO y en la prediccióndel riesgo de conversión a esclerosis múltiple.Recientemente se han incorporado nuevas técnicasexploratorias como la tomografia de coherenciaóptica, útil para el diagnóstico y pronóstico; se hanidentificado biomarcadores séricos que ayudan en eldiagnóstico de otras patologías de naturaleza autoinmuneque producen NO.Un mejor conocimiento de los datos clínicos y exploratoriosde la NO típica permitirá un estudio diagnósticomás rápido y certero. El tratamiento de la NOcon esteroides debe ser individualizado teniendo encuenta que no modifican el pronóstico a largo plazo yen pacientes con alto riesgo de conversión a esclerosismúltiple debe plantearse terapia inmunomoduladora.Este trabajo revisa los datos existentes en la literaturareferentes a las manifestaciones clínicas, el diagnósticoetiológico y diferencial y tratamiento de la NO inflamatoria(AU)

Inflammatory Optic Neuritis (ON) is the mostfrequent cause of acute visual loss in young adults.Although the visual prognosis is excellent in the majorityof cases, many patients develop pathology, such asmultiple sclerosis, in its subsequent evolution.The natural history of ON has been studied in numerousworks in recent years; one of the most importantof which is Optic Neuritis Treatment Trial.Magnetic Resonance plays a fundamental role inthe etiological diagnosis of ON and in predicting therisk of conversion into multiple sclerosis.New exploratory techniques have recently beenincorporated, such as optical coherence tomography,useful for diagnosis and prognosis; serum biomarkershave been identified in the diagnosis of other pathologieswith an autoimmune nature that produce ON.A better understanding of the clinical and exploratorydata of typical ON will make a more rapid and accuratediagnostic study possible. Treatment of ON withsteroids must be individualised bearing in mind thatthey do not alter the long-term prognosis and an immunomodulatingtherapy must be proposed for patientswith a high risk of conversion into multiple sclerosis.This article reviews the existing data in the literatureon its clinical manifestations, its etiological and differentialdiagnosis, and the treatment of inflammatory ON(AU)

[Emergencies in neuromuscular pathology]. / Urgencias en patología neuromuscular.

Acute muscle weakness (AMW) is the predominant symptom of neuromuscular emergencies, especially if it affects the respiratory or oropharyngeal musculature . AMW is a multi-etiological syndrome, with different lesion levels in the motor unit. Within the broad group of neuromuscular diseases, those that most frequently provoke AMW and respiratory failure are Guillain-Barré syndrome (GBS) and myasthenia gravis (MG). GBS is the most frequent cause of acute flaccid paralysis; it can cause respiratory failure in a third of cases, making mechanical ventilation necessary. Accurate diagnosis of this syndrome enables immunomodulatory treatment to be started, which has been shown to modify the course of the disease. Besides, clinical evaluation of the patients and knowledge of the simple tests of neurophysiology and respiratory function will guide the decision on mechanical ventilation, avoiding emergency intubation. The most frequent emergency caused by MG is myasthenic crisis, defined by the deterioration in the bulbar function with acute respiratory insufficiency and risk of respiratory stoppage. This occurs in 15-20% of myasthenic patients and can be triggered by numerous factors. Besides early identification of the crisis, it is important to suppress the triggering factors and to provide measure of ventilatory support. Amongst the pharmacological measures, the most useful instruments at present are plasmapheresis and intravenous immunoglobulins; these treatments do not cancel the need for intensive vigilance and of checking for imminent signs of respiratory failure that will involve invasive or non-invasive ventilatory support.

Danon disease: a novel Lamp-2 gene mutation in a family with four affected members.

This is a report of a family with four members affected with Danon disease and variable clinical presentations, including cardiomyopathy, skeletal muscle pathology, and hepatopathy. Analysis by electron microscopy of the quadriceps muscle from the proband and his brother showed abnormal mitochondria, and immunohistochemistry revealed no expression of LAMP-2 protein. This defect is due to a yet undescribed mutation located at the second nucleotide in the intron 8 of the Lamp-2 gene (c.1093+2 T>A) that generated exon 8 skipping confirmed at RNA level in the proband.

Urgencias en patología neuromuscular / Emergencies in neuromuscular pathology

La debilidad muscular aguda (DMA) es el síntoma predominante de las urgencias neuromusculares, especialmente si afecta a la musculatura respiratoria u orofaríngea. La DMA es un síndrome plurietiológico y con distintos niveles lesionales en la unidad motora. Dentro del amplio grupo de enfermedades neuromusculares, las que con mayor frecuencia provocan DMA e insuficiencia respiratoria son el síndrome de Guillain-Barré (SGB) y la miastenia gravis (MG). El SGB constituye la causa más frecuente de parálisis flácida aguda; puede ocasionar fallo respiratorio en un tercio de los casos precisando ventilación mecánica. El diagnóstico preciso de este síndrome permitirá iniciar tratamiento inmunomodulador, que ha demostrado que modifica el curso de la enfermedad. Además, la valoración clínica de los pacientes y el conocimiento de sencillos tests neurofisiológicos y de función respiratoria guiarán la decisión de ventilación mecánica evitando la intubación de urgencia. La urgencia más frecuente que ocasiona la MG es la crisis miasténica, definida por el deterioro en la función bulbar con insuficiencia respiratoria aguda y riesgo de parada respiratoria. Ocurre en un 15-20% de pacientes miasténicos y puede desencadenarse por múltiples factores. Además del diagnóstico preciso de la crisis es importante la supresión de los factores desencadenantes y medidas de soporte ventilatorio. Entre las medidas farmacológicas son la plasmaféresis y las inmunoglobulinas intravenosas los instrumentos más útiles en la actualidad; estos tratamientos no sustituyen la vigilancia intensiva y el reconocimiento de los signos inminentes de fallo respiratorio que implican soporte ventilatorio invasivo o no invasivo (AU)

Acute muscle weakness (AMW) is the predominant symptom of neuromuscular emergencies, especially if it affects the respiratory or oropharyngeal musculature . AMW is a multi-etiological syndrome, with different lesion levels in the motor unit. Within the broad group of neuromuscular diseases, those that most frequently provoke AMW and respiratory failure are Guillain-Barré syndrome (GBS) and myasthenia gravis (MG). GBS is the most frequent cause of acute flaccid paralysis; it can cause respiratory failure in a third of cases, making mechanical ventilation necessary. Accurate diagnosis of this syndrome enables immunomodulatory treatment to be started, which has been shown to modify the course of the disease. Besides, clinical evaluation of the patients and knowledge of the simple tests of neurophysiology and respiratory function will guide the decision on mechanical ventilation, avoiding emergency intubation. The most frequent emergency caused by MG is myasthenic crisis, defined by the deterioration in the bulbar function with acute respiratory insufficiency and risk of respiratory stoppage. This occurs in 15-20% of myasthenic patients and can be triggered by numerous factors. Besides early identification of the crisis, it is important to suppress the triggering factors and to provide measure of ventilatory support. Amongst the pharmacological measures, the most useful instruments at present are plasmapheresis and intravenous immunoglobulins; these treatments do not cancel the need for intensive vigilance and of checking for imminent signs of respiratory failure that will involve invasive or non-invasive ventilatory support (AU)

[Sleep disorders in prion diseases]. / Patología del sueño en las enfermedades priónicas.

Prion diseases are a group of encephalopathies with neurodegenerative changes caused by an altered protein named prion whose characteristic datum is transmissibility. In most cases they occur in a sporadic form although a group of them are familial associated with mutations in the gene of the prion protein. Genetic polymorphism seems to determine the different family variants. One of the most enigmatic and unusual is Fatal Familial Insomnia (FFI), a hereditary disorder characterised by loss of physiological sleep with oneiric stupor, autonomic and motor hyperactivity, and motor anomalies. The polysomnography of this entity reflects an inability to produce the physiological pattern of NREM and REM sleep, as well as hormonal and vegetative circadian fluctuations; the transition from wakefulness to sleep is markedly altered with the early disappearance sleep spindles. The hypothesis of the origin of these disorders is thalamic neuronal loss, especially in the anterior and dorsomedial nuclei, described in the neuropathology of these patients; besides PET reveals hypofunction of thalamic nuclei, centres responsible for controlling wakefulness-sleep. In Creutzfeldt-Jakob disease the wake-sleep disorders are not considered characteristic; nonetheless, frequent alterations have been found in the electroencephalographic registers of sleep. Besides thalamic neurodegeneration, there could be common etiopathogenic mechanisms in prion diseases in relation to the biological function of the prion protein.

Patología del sueño en las enfermedades priónicas / Sleep disorders in prion diseases

Las enfermedades priónicas son un grupo de encefalopatías con cambios neurodegenerativos causados por una proteína alterada denominada prión cuyo dato característico es la transmisibilidad. Ocurren la mayoría de las veces de forma esporádica aunque un grupo de ellas son familiares asociadas a mutaciones en el gen de la proteína priónica. El polimorfismo genético parece determinar las diferentes variantes familiares. Una de las más enigmáticas e inhabituales es el Insomnio Letal Familiar (ILF), trastorno hereditario caracterizado por pérdida del sueño fisiológico con estupor onírico, hiperactividad autonómica y motora, y anomalías motoras. La polisomnografía de esta entidad refleja la incapacidad para producir un patrón fisiológico del sueño NREM y REM, así como de las fluctuaciones circadianas hormonales y vegetativas; la transición de vigilia a sueño está marcadamente alterada con desaparición precoz de los husos de sueño. La hipótesis del origen de estos trastornos es la pérdida neuronal talámica, especialmente en los núcleos anterior y dorsomedial, descrita en la neuropatología de estos pacientes; además la PET revela hipofunción de núcleos talámicos, centros responsables del control vigilia-sueño. En la enfermedad de Creutzfeldt-Jakob las alteraciones de sueño-vigilia no se han considerado características, no obstante, se han encontrado frecuentes alteraciones en los registros electroencefalográficos de sueño. Además de la neurodegeneración talámica puede haber mecanismos etiopatogénicos comunes en las enfermedades priónicas en relación con la función biológica de la proteína priónica

Prion diseases are a group of encephalopathies with neurodegenerative changes caused by an altered protein named prion whose characteristic datum is transmissibility. In most cases they occur in a sporadic form although a group of them are familial associated with mutations in the gene of the prion protein. Genetic polymorphism seems to determine the different family variants. One of the most enigmatic and unusual is Fatal Familial Insomnia (FFI), a hereditary disorder characterised by loss of physiological sleep with oneiric stupor, autonomic and motor hyperactivity, and motor anomalies. The polysomnography of this entity reflects an inability to produce the physiological pattern of NREM and REM sleep, as well as hormonal and vegetative circadian fluctuations; the transition from wakefulness to sleep is markedly altered with the early disappearance sleep spindles. The hypothesis of the origin of these disorders is thalamic neuronal loss, especially in the anterior and dorsomedial nuclei, described in the neuropathology of these patients; besides PET reveals hypofunction of thalamic nuclei, centres responsible for controlling wakefulness-sleep. In Creutzfeldt-Jakob disease the wake-sleep disorders are not considered characteristic; nonetheless, frequent alterations have been found in the electroencephalographic registers of sleep. Besides thalamic neurodegeneration, there could be common etiopathogenic mechanisms in prion diseases in relation to the biological function of the prion protein

[Rhombencephalitis caused by Listeria: clinical-radiological correlation]. / Rombencefalitis por Listeria: correlación clínico-radiológica.

Rhombencephalitis due to Listeria is a serious and infrequent infection of the brainstem. It principally affects subjects who were previously healthy. It shows itself clinically in two phases: the first with unspecific symptoms, which could last one week, and the second with the appearance of focal neurologic signs at the level of the brainstem. We present the case of a patient with rhombencephalitis due to Listeria that began initially with headache, nauseas and fever and after ten days the patient showed an asymmetrical affection of cranial nerves, cerebellar signs and sensory deficits in the left hemibody. Subsequently this became complicated with acute respiratory insufficiency, requiring admission to the Intensive Care Unit, and with episodes of urinary retention that required exploration. The early magnetic resonance image showed hypertense patch lesions that were objectified in T2 sequences at the level of the bulb and the pons. Facing a clinical-radiological suspicion of rombencephalitis due to Listeria, treatment was begun with ampicillin and tombramycin. After some days a positive haemoculture for Listeria monocytogenes serotype 4B resistant to ampicilin was detected, therefore it was replaced with vancomycin. The patient survived and on discharge he had oculomotor disorder and micturition problems as sequels. We would like to emphasise the importance of early recognition of the clinical signs of the disease and the early permormance of magnetic resonance, with diagnostic support, to be able to start a suitable antibiotic treatment as quickly as possible.

[Paraneoplasic polyneuropathy with anti-amphiphysin antibodies]. / Polineuropatía paraneoplásica con anticuerpos anti-anfifisina.

Paraneoplastic neurological syndromes consist of a dysfunction of any part of the nervous system, in isolation or in combination, caused by a malign neoplasia, but not by the direct tissular or metastasic invasion of the tumour. Their pathogeny is explained by immunological mechanisms and they are characterised by the presence of high rates of antibodies in serum and cerebrospinal fluid. We present the case of a patient with a sensitive neuropathy that produced ataxia, and who suffered from a poorly differentiated adenocarcinoma of the lung, in whom the search for antineuronal antibodies was positive for antiamphiphysin antibodies, supporting the diagnosis of paraneoplastic polyneuropathy.

Rombencefalitis por Listeria: correlación clínico-radiológica / Rhombencephalitis caused by Listeria: clinical-radiological correlation

La rombencefalitis por Listeria es una infección grave e infrecuente del tronco cerebral. Afecta principalmente a sujetos previamente sanos. Clínicamente se manifiesta en dos fases: la primera con síntomas inespecíficos, de una semana aproximadamente de duración y la segunda con aparición de signos de focalidad neurológica a nivel del tronco cerebral. Presentamos el caso de un paciente con rombencefalitis por Listeria que inicialmente debutó con cefalea, náuseas y fiebre y a los diez días comenzó con afectación de pares craneales asimétrica, signos cerebelosos y alteraciones sensitivas en hemicuerpo izquierdo. Posteriormente se complicó con insuficiencia respiratoria aguda que precisó ingreso en Unidad de Cuidados Intensivos y con episodios de retención urinaria que requirieron sondaje. En la resonancia magnética cerebral realizada de forma precoz se objetivaron lesiones parcheadas hiperintensas en secuencias T2 al nivel de bulbo y protuberancia. Ante la sospecha clínico-radiológica de rombencefalitis por Listeria se inició tratamiento con ampicilina y tobramicina. A los días se detectó hemocultivo positivo para Listeria monocytogenes serotipo 4B resistente a ampicilina, por lo que se sustituyó por vancomicina. El paciente sobrevivió quedando al alta como secuelas trastorno oculomotor y molestias miccionales. Como conclusión destacamos la importancia del reconocimiento temprano de los signos clínicos de la enfermedad y de la realización de forma precoz de resonancia magnética, como apoyo diagnóstico, para poder instaurar lo antes posible el tratamiento antibiótico adecuado (AU)

Polineuropatía paraneoplásica con anticuerpos anti-anfifisina / Paraneoplasic polyneuropathy with anti-amphiphysin antibodies

Los síndromes paraneoplásicos neurológicos consisten en la disfunción de cualquier parte del sistema nervioso de forma aislada o en combinación causada por una neoplasia maligna, pero no por la invasión tisular directa o metastásica del tumor. Su patogenia se explica por mecanismos inmunológicos y se caracterizan por la presencia de títulos altos de anticuerpos en suero y líquido cefalorraquídeo. Presentamos el caso de un paciente con una neuropatía sensitiva que producía ataxia y que padecía un adenocarcinoma de pulmón poco diferenciado en el que la búsqueda de anticuerpos antineuronales fue positiva para anticuerpos anti-anfifisina, apoyando el diagnóstico de polineuropatía paraneoplásica (AU)

[Internal carotid stenosis and giant cell arteritis]. / Estenosis de arteria carótida interna y arteritis de células gigantes.

We report on the case of a 69-year-old man admitted with a transient ischemic attack preceded by a two months history of severe headache. Giant cell arteritis was diagnosed by means of temporal artery biopsy. Angiography showed an intra- and extracranial stenosis of the left internal carotid artery. The possible relationship between this stenosis and vasculitis is discussed and stroke as a clinical manifestation of the giant cell arteritis is reviewed.

Acute carotid obliteration: a new vascular manifestation in POEMS syndrome.

The case of a 65-year-old woman with polyneuropathy, organomegaly, skin changes and monoclonal gammopathy of IgG-lambda type is described. This patient developed an acute carotid obliteration during oral anticoagulation and despite absence of vascular risk factors. Macroangiopathy has been described as a rare systemic manifestation of POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal spike and skin changes), affecting the coronary and lower limbs arteries. To our knowledge, this is the second case of POEMS syndrome with a cerebrovascular manifestation.

Ataques isquémicos transitorios / Transitory ischaemic attacks

No disponible

[A review of the pathogenesis of the hallucinatory state. A description of four case]. / Revisión sobre la patogenia del estado alucinatorio. Aportación de 4 casos.

INTRODUCTION: A hallucination is a sensorial experience occurring in the absence of external stimuli. It may show as psychological or organic disorders. The main causes are lesions of the central nervous system and of the sensorial organs. The hallucination may present with or without critical perception but always appears to be a real experience. CLINICAL CASE: We describe four patients diagnosed as having hallucinations secondary to known lesions. The first two had visual hallucinations and cerebral ischaemia, the first in the dorso-lateral region of the medulla oblongata and the second in the left parietal lobe. The other two had peripheral sensorial defects. The third patient had simultaneously an ophthalmic disorder and visual hallucinations, and the fourth had chronic hypoacusia and auditory hallucinations. All showed structured sensorial hallucinations with critical appraisal of these hallucinations. CONCLUSIONS: In this paper we review the pathogenesis of the organic hallucinatory state. The main mechanisms are proposed: by means of liberation (destruction of inhibitory structures) and by means of irritation (anomolous excitation of cerebral structures). Also we point out the difference between a hallucination and psychiatric disorders, mainly in three aspects: presence of the known organic lesion, critical appraisal of the perception in spite of it appearing as real to the patient, and the absence of associated psychiatric pathology.