The view of experts on initiatives to be undertaken to promote equity in the access to orphan drugs and specialised care for rare diseases in Spain: A Delphi consensus.

OBJECTIVES: To reach a consensus amongst experts on the most feasible actions to be undertaken to facilitate patient access to specialised care and orphan drugs (OD) in the public health sector in Spain. METHODS: Two Delphi rounds were completed. The questionnaire was based on a literature review and 2 focus groups. Agreement was sought on the desire (D) and prognosis (P) for the implementation within the next 5 years, on a 5-point Likert scale. Consensus was reached when ≥75% participants chose agreement (1-2) or disagreement options (4-5). RESULTS: 82 experts on rare disease (RD) participated. Agreement on the D and P was reached in 66.07% statements: OD pricing review [absence of clinical effectiveness (D:85.37%; P:85.90%), target population increase (D:79.27%; P:91.03%)]; reference team definition of referral protocols and clinical practice guidelines (D: 97.56%; P: 89.74%); and a unified, usable, etiology-based registry (D:97.56%; P:84.62%). D and P assessment diverged in 32.14% items: creation of a specific funding system for OD (D: 97.56%; P: 60.25%); and a network of medical teams to coordinate the care of RD patients (D: 99%; P: 62%). CONCLUSIONS: The results have shown the need to promote dialogue between stakeholders, introduce European recommendation to national and regional Spanish policies and set up priorities and undertake actions to drive relevant changes in current medical practice in managing RD patients.

[Novel therapies in neurometabolic diseases: the importance of early intervention]. / Terapias novedosas en enfermedades neurometabolicas: importancia de una intervencion precoz.

INTRODUCTION: Individually, neurometabolic diseases are ultra rare, but for some of them there is an effective treatment. DEVELOPMENT: Several recent therapeutic advances are reviewed. Today, the possibilities of treatment for lysosomal diseases have improved. In recent years the use of enzyme replacement therapy has become more widely extended to treat mucopolysaccharidosis type IVA (Morquio A), mucopolysaccharidosis type VII (Sly syndrome), lysosomal acid lipase deficiency and alpha-mannosidosis. It has been proven that very early treatment of mucopolysaccharidoses can change their natural course. Intrathecal enzyme replacement therapy is being tried in some mucopolysaccharidoses with cognitive involvement, in an attempt to halt neurodegeneration. Very positive results have been obtained with genetically modified autotransplants in late-onset infantile metachromatic leukodystrophy and research is being conducted on other pathologies (mucopolysaccharidosis type III, X-linked adrenoleukodystrophy). Novel outcomes are also being achieved in the treatment of some encephalopathies that are sensitive to vitamins or cofactors: triple therapy in pyridoxine dependency, treatment with thiamine for some subacute encephalopathies with involvement of the basal ganglia, treatment with folinic acid for children with cerebral folate deficiency, or treatment with cyclic pyranopterin monophosphate in molybdenum cofactor deficiency type A. CONCLUSIONS: As neuropaediatricians we must update our knowledge, especially in the case of treatable neurometabolic pathologies, since early treatment can change their prognosis significantly.

TITLE: Terapias novedosas en enfermedades neurometabolicas: importancia de una intervencion precoz.Introduccion. Las enfermedades neurometabolicas son individualmente ultrarraras, pero algunas de ellas tienen un tratamiento eficaz. Desarrollo. Se revisan algunas novedades terapeuticas. Las enfermedades lisosomales tienen actualmente mejores posibilidades de tratamiento. En los ultimos años se ha extendido el uso de la terapia enzimatica sustitutiva a la mucopolisacaridosis tipo IVA (Morquio A), a la mucopolisacaridosis tipo VII (enfermedad de Sly), al deficit de lipasa acida lisosomal y a la alfa-manosidosis. Se ha constatado que un tratamiento muy precoz de las mucopolisacaridosis puede cambiar su historia natural. Se esta probando la terapia enzimatica sustitutiva intratecal en algunas mucopolisacaridosis con afectacion cognitiva, en el intento de frenar la neurodegeneracion. Se han obtenido resultados muy positivos con autotrasplante modificado geneticamente en leucodistrofia metacromatica infantil tardia y se esta trabajando en otras patologias (mucopolisacaridosis tipo III, adrenoleucodistrofia ligada a X). Tambien hay novedades en la terapia de algunas encefalopatias sensibles a vitaminas o cofactores: la triple terapia en la dependencia de piridoxina, el tratamiento con tiamina de algunas encefalopatias subagudas con afectacion de ganglios basales, el tratamiento con acido folinico de niños con deficiencia de folato cerebral, o el tratamiento con monofosfato de piranopterina ciclico en los defectos de cofactor de molibdeno de tipo A. Conclusiones. Los neuropediatras debemos actualizar nuestro conocimiento especialmente en aquellas patologias neurometabolicas tratables, dado que una terapia precoz puede cambiar de forma significativa su pronostico.

[Hemiconvulsion-hemiplegia syndrome: two case reports with findings from magnetic resonance imaging of the brain in diffusion-weighted sequences]. / Síndrome hemiconvulsión-hemiplejía: presentación de dos casos con los hallazgos de resonancia magnética cerebral en secuencias potenciadas en difusión.

INTRODUCTION: Hemiconvulsion-hemiplegia (HH) syndrome is characterised by prolonged hemiclonic seizures followed by, very often permanent, hemiplegia. We report the cases of two patients with HH syndrome; in addition, the paper also includes a discussion of the value of neuroimaging in its diagnosis, including the use of magnetic resonance imaging (MRI) of the brain in diffusion-weighted sequences, and its clinical-radiological progression. CASE REPORTS: Case 1: a 16-month-old female who was admitted to hospital owing to right-side hemiclonic seizures, with a febrile condition, that lasted at least 30 minutes, and persistent hemiparesis on the right-hand side of the body. Results of an initial computerised tomography (CT) brain scan were normal. Brain MRI at 3 days: T2 weighted sequences were normal; diffusion-weighted sequences showed lowered diffusion in the temporoparietooccipital region in the left hemisphere. Brain CT scan at 6 months: hemiatrophy on the left-hand side of the brain. Paresis of the right hand continues at the age of 4 years and 8 months; no further seizures have occurred and the patient's psychic development is normal. Case 2: a female aged 2 years and 6 months who was admitted to the Paediatric Intensive Care Unit owing to right-side hemiclonic seizures, with a feverish condition, lasting between 35-40 minutes, with persistent hemiplegia on the right-hand side of the body. The patient had a history of psychomotor retardation secondary to chromosome pathology; findings from a brain CT scan were normal. CT scan at 48 hours after the episode: edema in the left hemisphere of the brain. Brain MRI at 7 days following hospital admission: extensive involvement of the left hemisphere of the brain could be seen in T2 weighted sequences and in diffusion-weighted sequences. CT scan at 3 months: hemiatrophy on the left-hand side of the brain. Hemiparesis persists at the age of 5 years and 4 months; the patient has had no further seizures and attends specialised schooling. CONCLUSION: Although rare in our environment, HH syndrome can be seen in the context of hemiclonic febrile conditions. MRI of the brain in diffusion-weighted sequences may be the only means of proving the initial brain lesion.

[Intrathecal baclofen therapy: the selection of patients and short term results in five patients]. / Terapia con baclofén intratecal: selección de pacientes y resultados a corto plazo en cinco pacientes.

INTRODUCTION: Intrathecal baclofen therapy (ITB) is a new tool in the integrated treatment of childhood spasticity. AIMS. We describe the eligibility and exclusion criteria used in the study and short term results of ITB therapy in our first five patients are also reported. PATIENTS AND METHODS: Our sample of patients consisted of three females and two males aged between 14 and 17 years. Two of them were ambulant (one without help and the other with crutches), two were serious non ambulant tetraparetics and the other was in a wheelchair but minimally ambulant. All of them satisfied our eligibility criteria. The main aims set out were to improve walking in the three patients with less serious involvement and to reduce or eliminate the pain and enhance quality of life (QOL) in the two more seriously affected patients. In all cases, the Baclofen test was positive. RESULTS: Follow up time was between 2 and 5 months. The objectives appear to have been accomplished, for the time being, in three patients: the two ambulant patients improved their capacity to walk and one male with serious spastic tetraparesis and pain no longer suffers from that pain and his QOL has improved. There were mild transient side effects in three patients. CONCLUSION: The selection of patients, including the definition of realistic tailor made objectives, is an essential step in ITB therapy. Results in our series, in the short term, indicate that ITB therapy can be efficient in ambulant and non ambulant patients, and offers few side effects.

[Cerebral malaria in children]. / Neuropaludismo infantil.

INTRODUCTION: Malaria is one of the main health problems in the Third World. Plasmodium falciparum infects as many as 300 million people, causing up to three million deaths each year, most of which occur in African children. Cerebral malaria is the most common lethal complication of P. falciparum infection in children and is defined by three criteria: disturbances of consciousness, presence of P. falciparum parasitaemia and absence of other causes of acute encephalopathy. Cerebral malaria is a medical emergency and parenteral quinine is the most recommended treatment because of the frequency of chloroquine-resistant strains. Mortality is as high as 50 per cent and residual disability is present in about 20 per cent of survivors. OBJECTIVE: We want to warm Spaniard neuropaediatricians about the existence of cases of cerebral malaria in our country in order to get a better diagnose and treatment for those children. PATIENTS AND METHODS: A retrospective medical scores review of 20 hospitalised children diagnosed of malaria from 1990 to 1998. We selected three cases with neurological signs and we analysed clinical onset, EEG, neuroimaging, and permanent sequels. RESULTS: All patients had acute encephalopathy with fever, obtundation and seizures. They all presented residual disability (mainly hemiparesis). CONCLUSION: We must know better about cerebral malaria because of an increasing incidence of imported malaria due to emigration from African countries and Spaniard tourism to areas of endemic paludism.

[Evolutive neuroradiological alterations in Sandhoff's disease]. / Alteraciones neurorradiológicas evolutivas en la enfermedad de Sandhoff.

Sandhoff's disease is a severe form of gangliosidosis GM2 which presents in the first year of life, basically as progressive psychomotor retardation and/or a macular red cherry spot. Our patient presented the clinical picture characteristic of the disease. Diagnosis was confirmed by determining the activity of hexosaminidases A and B in serum and of beta-N-acetil hexosaminases in fibroblast culture. In view of the fatal prognosis of the disease, in 1991 a transplant of alogenic bone marrow (TMO) was carried out to try to replace the enzymes. This required exhaustive radiological follow-up to determine the possible neuro-radiological changes seen in this storage disease. Although treatment was not successful, the neuro-radiological findings may be of interest as perhaps being characteristic of the GM2 gangliosidosis: 1. Bilateral thalamic hyperecogenity in the cerebral ecography. 2. Differences between the thalamo-putamen densities due to bilateral homogeneous thalamic hyperdensity on the CT scan. 3. Thalamic hypointensity both on T2 sequences and in proton density on MR with the cerebral white matter being progressively affected. In conclusion, we suggest that bilateral symmetrical thalamic changes are an early finding which is probably specific to the GM2 gangliosidoses and may be useful from the point of view of carrying out more specific investigations in infants suspected of having a degenerative neurological disorder.

[Gerstmann's syndrome in a 9 year old boy]. / Síndrome de Gerstmann en un varón de 9 años.

INTRODUCTION: Gerstmann's syndrome encompasses the tetrad of finger agnosia, agraphia, acalculia and right-left confusion and is associated with lesions of the left angular gyrus, situated at the confluence of the temporal, parietal and occipital lobes. The localizing value of this syndrome has been questioned because multiple mechanisms can account for each of the four components of the syndrome. This clinical association is infrequent in children and it is impossible to diagnose in early stages of life because of parietal lobes have a slow functional development during childhood. CLINICAL CASE: We present the case of a learning disabled boy, 9 year old and right handed, who developed Gerstmann's syndrome. Acalculia, right-left disorientation, agraphia and finger agnosia were clearly identified by neuropsychological studies at this time, but there was no evidence of this dysfunction when he was first studied being 5 year old. This patient had perinatal asphyxia and suffered from focal clonic seizures in early neonatal period. In this case, a infarcted lesion was found at the confluence of parietal and occipital lobes in cranial CT an MRI scans. CONCLUSION: We conclude that is very important to identify this syndrome during childhood using a wide range of neuropsychological tests in order to diminish learning disorders with an early psychopedagogic supervision.

[A case of mixed (parenchymatous meningo-basal) neurocysticercosis]. / Presentación de un caso de neurocisticercosis mixta (parenquimatosa-meningobasal).

INTRODUCTION: Cysticerosis is the commonest parasitic disease to affect the central nervous system (CNS). Distribution is universal. It is endemic in many developing countries and in the Third World. CNS cysticercoses or neurocysticercosis may be classified according to its site in three main groups: parenchymatous, extra-parenchymatous and mixed. The clinical features vary from casual findings to fulminating encephalitis. The commonest presenting symptoms are intracranial hypertension (HIC) in the extra-parenchymatous forms and convulsions in the parenchymatous forms. CLINICAL CASE: We present the case of an eight-year-old Peruvian boy with the clinical features of progressive intracranial hypertension. Cerebro-spinal fluid (CSF) serological and neuro-imaging findings were compatible with mixed neurocysticercosis (parenchymatous calcifications and an active meningobasal lesion). We also describe the neuro-radiological changes seen in the course of the illness of our patient after treatment with albendazol. These are mainly the reduction in size and progressive calcification of the active meningobasal lesion. CONCLUSIONS: We propose a neuro-radiological classification based on that of Carpio et al as a method of helping to decide on anti-parasitic treatment. We emphasize the importance of the findings on cranial magnetic resonance (MR), using gadolinium to differentiate the various stages of the disease. Finally, we draw attention to the possible increase in this disease in our environment, due to the current increase in migration from endemic areas of Latin America.

[Repeated cerebral infarction in a patient with Duchenne's muscular dystrophy]. / Infartos cerebrales de repeticion en un paciente con distrofia muscular de Duchenne.

INTRODUCTION: We describe a case of Duchenne muscular dystrophy (DMD) with multiple strokes related to dilated cardiomyopathy. CASE REPORT: A 13 year old boy, with advanced stage DMD was admitted to the hospital because of acute motor and sensory impairment in his right bodyside. Imaging study revealed lesions in basal ganglia and prerolandic cortex in the left hemisphere that were compatible with infarcts in the territory of the medial cerebral artery. Cardiologic evaluation revealed dilation of the left ventriculi and systolic dysfunction with ejection fraction of 35 40%. The symptoms evolved to a residual right hemiparesia. Five months later, the patient developed a transient episode of aphasia and the study performed in this case revealed lesions compatible with infarcts in basal ganglia and insular cortex of the right cerebral hemisphere. CONCLUSION: Cerebral infarction related to cardiomyopathy can worsen the clinical condition of patients with DMD. Early treatment of dilated cardiomyopathy with systolic dysfunction, including use of antithrombotic agents to prevent cerebrovascular complications, could help to improve the course of the disease.

[Two new cases of Leigh syndrome caused by mutation m.13513G> A in the MTND5 gene]. / Dos nuevos casos de sindrome de Leigh por mutacion m.13513G>A en el gen MTND5.

TITLE: Dos nuevos casos de sindrome de Leigh por mutacion m.13513G>A en el gen MTND5.

[Anti-NMDA receptor encephalitis with unilateral hemispheric affectation]. / Encefalitis por anticuerpos contra el receptor de NMDA con afectacion hemisferica unilateral.

TITLE: Encefalitis por anticuerpos contra el receptor de NMDA con afectacion hemisferica unilateral.

First experience of enzyme replacement therapy with idursulfase in Spanish patients with Hunter syndrome under 5 years of age: case observations from the Hunter Outcome Survey (HOS).

Hunter syndrome (mucopolysaccharidosis type II [MPS II], OMIM309900) is a rare X-linked lysosomal storage disorder caused by deficiency of the enzyme iduronate-2-sulphatase, resulting in accumulation of glycosaminoglycans (GAGs), multisystem organ failure and early death. Enzyme replacement therapy (ERT) with idursulfase is commercially available since 2007. Early access programs were established since 2005. However, limited information on the effects of ERT in young children is available to date. The aim of this analysis was therefore to determine the effects of ERT on patients younger than 5 years of age. We report data from six Spanish patients with confirmed Hunter syndrome who were younger than 5 years at the start of ERT, and had been treated with weekly intravenous infusions of idursulfase between 6 and 14 months. Baseline and treatment data were obtained from the Hunter Outcome Survey (HOS). HOS is an international database of MPS II patients on ERT or candidates to be treated, that collects data in a registry manner. HOS is supported by Shire Human Genetic Therapies, Inc. (Cambridge, MA, USA). At baseline, all patients showed neurological abnormalities, including ventriculomegaly, hydrocephaly, cerebral atrophy, perivascular changes and white matter lesions. Other signs and symptoms included thoracic deformity, otitis media, joint stiffness and hepatosplenomegaly, demonstrating that children under 5 years old can also be severely affected. ERT reduced urinary GAG levels, and reduced spleen (n = 2) and liver size (n = 1) after only 8 months. Height growth was maintained within the normal range during ERT. Joint mobility either stabilized or improved during ERT. In conclusion, this case series confirms the early onset of signs and symptoms of Hunter syndrome and provides the first evidence of ERT beneficial effects in patients less than 5 years of age. Similar efficacy and safety profiles to those seen in older children can be suggested, although further studies including a direct comparison with older patients would still be required.

[Para-infectious seizures in children: a retrospective study of 34 cases]. / Crisis parainfecciosas en el niño: estudio retrospectivo de 34 casos.

INTRODUCTION: Para-infectious seizures are afebrile convulsions that are associated with banal infectious processes and have a good overall prognosis. AIM: To determine the natural history of para-infectious seizures in children. PATIENTS AND METHODS: We conducted a retrospective study of children who were admitted to our hospital between January 2000 and January 2005 with seizures associated to an infectious process that did not satisfy the criteria of febrile seizures. Data collected included age, sex, season of the year, personal and familial history, type of infection, symptoms of the seizures, complementary examinations, treatments that were used and progression. RESULTS: The sample finally included 22 girls and 12 boys with ages ranging from 6 to 38 months (mean: 20.26 +/- 8.29 months) and previous psychomotor development was seen to be normal. Three of them had a family history of epilepsy and three others had suffered previous febrile seizures. Twenty-three children developed seizures associated to gastroenteritis and in 11 cases they were linked to upper respiratory infections. The average interval between onset of the infection and seizures was 2.26 days, and the average number of seizures was 3.38. Eight patients had recurring seizures (23.5%), usually in the form of para-infectious or febrile seizures, and secondary seizures were observed in only one case. CONCLUSIONS: It is important to be familiar with this condition because many of these patients are initially diagnosed with an encephalitic syndrome. These seizures are usually associated with gastroenteritis, with cluster seizures and with normal later psychomotor development. The risk of developing secondary seizures developmentally is low.

[Clinical study of enzyme replacement therapy with idursulfase]. / Experiencia clínica del tratamiento de sustitución enzimática con idursulfasa.

INTRODUCTION: Important advances have been made in enzyme replacement therapy in the treatment of lysosomal diseases over the last two decades. Here we review the initial ERT trial using idursulfase in Hunter syndrome (mucopolysaccharidosis type II) and we also examine relevant aspects of the use of this enzyme. DEVELOPMENT: A preclinical trial in a knockout mouse showed a decrease in glycosaminoglycans, both in urine and in tissues, following treatment with idursulfase. In a randomised, double-blind, placebo-controlled clinical study in phase I/II conducted in 12 patients with Hunter syndrome, treatment with idursulfase displayed a good safety profile and also a decrease in the excretion of glycosaminoglycans and cases of visceromegaly. The 12 patients continued the study in an open manner for two years and favourable outcomes were also obtained. A recent randomised, double-blind, placebo-controlled, multi-centre and multinational study in phase II/III conducted with 96 patients with Hunter syndrome over one year showed that the administration of 0.5 mg/kg doses of idursulfase significantly improved the final 'combined' score, which was the sum of the changes in the percentage of predicted forced vital capacity and in the 6-minute walk test, in comparison to the response obtained with a placebo. This result was the same for the weekly treatment group (p = 0.0049) and the fortnightly group (p = 0.0416). Many of the secondary effectiveness parameters also improved significantly, especially in the weekly treatment group. Treatment with idursulfase was well tolerated, with side effects that were, generally speaking, mild or moderate. IgG antibodies were detected in up to 46.9% of the patients treated in the two groups, but no apparent relation with the side effects or the clinical response was observed. CONCLUSIONS: Treatment with 0.5 mg/kg of idursulfase in weekly intravenous infusions is usually well tolerated and seems to improve the somatic symptoms in patients with mucopolysaccharidosis type II.

[Advances in the treatment of lysosomal diseases in infancy]. / Avances en el tratamiento de las enfermedades lisosomales en la infancia.

AIMS: The treatment of lysosomal diseases has undergone a number of significant changes in recent decades. Here we review the different therapeutic approaches that can be used: the well-consolidated haematopoietic stem-cell transplants (HST) and enzyme replacement therapy (ERT), the new therapeutic strategies with small molecules such as substrate reduction therapy (SRT) or enzyme 'enhancement' therapy (EET) and experimental approaches like gene therapy. DEVELOPMENT: We review the status of ERT in general and more particularly in Gaucher disease, Fabry disease, mucopolysaccharidosis type I, Pompe disease and the first stages of Hunter disease and Maroteaux-Lamy syndrome. Their outcomes, indications, safety and side effects are also evaluated. We examine the value of HST in these diseases and more particularly in Hurler syndrome, Maroteaux-Lamy syndrome, globoid cell leukodystrophy, metachromatic leukodystrophy and Gaucher disease. The initial results from using SRT, EET and with gene therapy are briefly outlined. CONCLUSIONS: A great deal of progress has been made in the treatment of some lysosomal diseases in recent decades due to careful use of HST and ERT. Furthermore, the application of the latest therapeutic instruments such as SRT and EET opens up new perspectives in this field.

[Recurrent infection of the urinary tract in girls]. / Infección recurrente del tracto urinario en niñas.

A group of 18 girls, studied in a period between 1979 and 1985 with recurrent urinary tract infections (RUTI), with at least three culture documented episodes of bacteriuria in the previous year and without radiologic evidence of urinary tract abnormality is described. Incidence was 6.1% amount a selected group of 295 girls with urinary tract infection. The period of follow-up was between 2 and 6 years (X 3.33). Symptomatology was light. No predominance of urinary symptoms were found. E. coli was the most frequent germ isolated. The number of recurrences/year/girl were significantly lower with prophylactic treatment and with years of evolution. Renal damage was not found. Vesicoureteral reflux appeared in two girls only. They had a benign course and a good prognosis. Reduction of aggressive investigation in this group of patients is proposed.

CNS sequelae in Langerhans cell histiocytosis: progressive spinocerebellar degeneration as a late manifestation of the disease.

Central nervous system involvement in Langerhans cell histiocytosis (LCH), formerly known as histiocytosis X, is manifested mainly by diabetes insipidus reflecting local infiltration of Langerhans cells into the posterior pituitary or hypothalamus. We describe two patients with progressive spinocerebellar degeneration appearing 4 and 6 years after the initial diagnosis of LCH. No correlation was found between the clinical course of the disease or its treatment and the neurological impairment. An extensive search for metabolic, toxic, neoplastic, and hereditary etiologies for progressive cerebellar degeneration was negative.

[Angelman syndrome. Early diagnosis]. / Síndrome de Angelman. Diagnóstico precoz.

We report two patients who were less than two years old that were diagnosed as having Angelman syndrome. Cytogenetic confirmation of the disease was performed. We emphasize clinical and electroencephalographic features in infants that allow an early diagnosis of this syndrome and allow for prompt genetic counseling.

Análisis de una serie de casos con diagnóstico inicial de encefalomielitis aguda diseminada en el período 2000-2010 / Analysis of a series of cases with an initial diagnosis of acute disseminated encephalomyelitis over the period 2000-2010

Introducción. La encefalomielitis aguda diseminada (EMAD) es una enfermedad desmielinizante que afecta fundamentalmente a la sustancia blanca del sistema nervioso central. El diagnóstico se basa en hallazgos clinicorradiológicos y evolutivos. La resonancia magnética cerebral es la herramienta diagnóstica más útil. El curso suele ser monofásico y el tratamiento inicial de elección, los corticoides.Pacientes y métodos. Estudio retrospectivo de 18 pacientes con diagnóstico de sospecha inicial de EMAD. Se analizó la sintomatología, los hallazgos radiológicos, la evolución y el tratamiento. El diagnóstico definitivo se estableció en 12 pacientes, excluyendo un paciente con reacción en cadena de la polimerasa positiva para el virus herpes simple en el líquido cefalorraquídeo, uno con clínica compatible pero resonancia magnética cerebral normal, y cuatro con inicio similar a EMAD cuyos diagnósticos definitivos fueron: síndrome de Rassmusen, síndrome hemofagocítico, tumor cerebral y MELAS(encefalomiopatía mitocondrial con acidosis láctica y accidentes cerebrovasculares). Resultados. La mediana de edad fue de 31 meses, sin predominio de sexo. La infección de la vía respiratoria superior fue la causa más frecuente en niños mayores y la gastrointestinal, en menores de 2 años. Todos presentaron alteración en el nivel de conciencia y déficits neurológicos multifocales. El hallazgo radiológico más frecuente fue la alteración multifocal bihemisférica de la sustancia blanca. Los corticoides fueron el tratamiento de elección en la mayoría. La evolución fue favorable en casi todos los pacientes excepto en dos, que tuvieron secuelas importantes. Conclusiones. La EMAD puede presentarse a cualquier edad, incluyendo lactantes. Hay múltiples entidades que pueden simular una EMAD en un inicio (AU)

Introduction. Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease that essentially affects the white matter of the central nervous system. The diagnosis is based on clinical-imaging and developmental findings. Magnetic resonance imaging of the brain is the most useful diagnostic tool. The disease course is usually monophasic and the preferred initial treatment is with corticoids. Patients and methods. We conducted a retrospective study of 18 patients with a presumptive diagnosis of ADEM. Symptoms, imaging findings, progress and treatment were analysed. The definitive diagnosis was established in 12 patients, excluding one patient with positive polymerase chain reaction for herpes simplex virus in cerebrospinal fluid, one with a clinicalpicture that was consistent but normal magnetic resonance imaging of the brain, and four with an onset that was similar to ADEM whose definitive diagnoses were: Rassmusen’s syndrome, haemophagocytic syndrome, brain tumour, and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Results. The median age was 31 months with no predominance of either sex. Infection of the upper respiratory tract was the most frequent cause in children over 2 years of age and of the gastrointestinal tract in those under the age of 2. All of them presented altered levels of consciousness and multifocal neurological deficits. The most frequent imaging finding was multifocal alteration of the white matter in both hemispheres. Corticoids were the preferred treatment in most cases. Progression was favourable in nearly all patients except for two, who were left with important sequelae. Conclusions. ADEM may present at any age, including in infants. There are a number of conditions that can mimic ADEM in the early stages (AU)