[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.

[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.

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.

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)

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.

Manifestaciones neurológicas del síndrome de Hunter / Neurological manifestations of hunter syndrome

Introducción. La mucopolisacaridosis tipo II, o síndrome de Hunter, presenta con frecuencia manifestaciones neurológicas. Se revisan las diferencias entre el síndrome de Hunter grave y atenuado, las manifestaciones del sistema nervioso central y periférico, auditivas y visuales, así como las alteraciones observadas en la resonancia magnética craneal. Desarrollo. Se exponen las dificultades para diferenciar las formas graves y atenuadas de síndrome de Hunter, sobre todo en las formas fenotípicas ‘intermedias’. Se recogen las manifestaciones clínicas más destacadas y el manejo diagnóstico y terapéutico de la afectación cognitiva y conductual, la hidrocefalia, las crisis epilépticas, la compresión medular, los trastornos de la visión y la audición y el síndrome del túnel carpiano. Se analizan los resultados limitados y heterogéneos de los estudios de resonancia magnética craneal. Conclusiones. En el síndrome de Hunter grave, las alteraciones cognitivas y los trastornos de conducta protagonizan el período de neurodegeneración. La hipoacusia y el síndrome de túnel carpiano son frecuentes en el síndrome de Hunter grave y atenuado. Algunas complicaciones (hipoacusia, hidrocefalia, compresión medular, síndrome del túnel carpiano) presentan un mejor pronóstico si se detectan y tratan precozmente. En la actualidad no existe una clara correlación entre las alteraciones en la neuroimagen y la clínica. El estudio y seguimiento sistematizado y el tratamiento precoz sintomático y enzimático muy probablemente cambiarán la historia natural de muchos pacientes con síndrome de Hunter (AU)

Introduction. Mucopolysaccharidosis type II, or Hunter syndrome, often presents neurological manifestations. This study examines the differences between severe and mild Hunter syndrome and between central and peripheral nervous system as well as auditory and visual manifestations; it also looks at the alterations observed in magnetic resonance imaging of the head. Development. The difficulties involved in distinguishing between severe and mild forms of Hunter syndrome, above all in the ‘intermediate’ phenotypic forms, are also discussed. The study also reports the most notable clinical manifestations and the diagnostic and therapeutic management of the cognitive and behavioural disorders, hydrocephalus, epileptic seizures, spinal cord compression, visual and hearing disorders, and carpal tunnel syndrome. Finally, the limited, heterogeneous findings from magnetic resonance imaging of the head are analysed. Conclusions. In severe Hunter syndrome, the lead factors during the period of neurodegeneration are cognitive disorders and conduct disorders. Hypoacusis and carpal tunnel syndrome are frequent in both severe and mild Hunter syndrome. Some complications (hypoacusis, hydrocephalus, spinal cord compression, carpal tunnel syndrome) offer a better prognosis if they are detected and treated at an early stage. Currently there is no clear correlation between neuroimaging alterations and the clinical features. Systematic study and monitoring, together with early symptomatic and enzyme treatment are likely to change the natural history of many patients with Hunter syndrome (AU)

[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.

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

Las crisis parainfecciosas son crisis convulsivas afebriles que se asocian a procesos infecciosos banalesy tienen un buen pronóstico global. Objetivo. Conocer la historia natural de las crisis parainfecciosas en el niño. Pacientes y métodos. Estudio retrospectivo de los niños ingresados en nuestro hospital entre enero de 2000 y enero de 2005 con crisis convulsivas asociadas a un proceso infeccioso que no cumplían los criterios de las crisis convulsivas febriles. Se analizaron:edad, sexo, estación del año, antecedentes personales y familiares, tipo de infección, la semiología de la crisis, las exploraciones complementarias, tratamientos empleados y la evolución. Resultados. Se encontraron 22 niñas y 12 niños con edades comprendidas entre 6 y 38 meses (media: 20,26 ± 8,29 meses) con un desarrollo psicomotor previo normal. Tres de ellos tenían antecedentes familiares de epilepsia y tres más presentaban crisis febriles previas. Veintitrés niños desarrollaron crisis convulsivas asociadas a una gastroenteritis y 11 a una infección del tracto respiratorio superior. El intervalo promedioentre el inicio de la infección y la crisis fue de 2,26 días, y el número promedio de crisis, de 3,38. Ocho pacientes presentaron recurrencia de las crisis convulsivas (23,5%), habitualmente como crisis parainfecciosas o crisis febriles, y tan sólo en un casocomo crisis no provocadas. Conclusiones. Es importante conocer esta entidad dado que a muchos de estos pacientes se les diagnostica inicialmente síndrome encefalítico. Estas crisis suelen asociarse a gastroenteritis, con agrupación de crisis y conun desarrollo psicomotor posterior normal. El riesgo de presentar crisis no provocadas de forma evolutiva es bajo

Para-infectious seizures are afebrile convulsions that are associated with banal infectious processesand 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. Datacollected 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 12boys 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. Theaverage 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 secondaryseizures 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, withcluster 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.

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

Objetivo. El tratamiento de las enfermedades lisosomalesha experimentado cambios muy significativos en las últimas décadas.Se revisan las distintas vías de tratamiento: las ya consolidadascomo el trasplante de precursores hematopoyéticos (TPH) y la terapiade reemplazamiento enzimático (TRE), las nuevas estrategiasterapéuticas con pequeñas moléculas como la terapia de reducciónde sustrato (TRS) o la terapia de ‘mejora’ enzimática (TME) y lasexperimentales como la terapia génica. Desarrollo. Se revisa el estadode la TRE en general y en especial en la enfermedad de Gaucher,enfermedad de Fabry, mucopolisacaridosis tipo I, enfermedad dePompe y los primeros pasos en el síndrome de Hunter y el síndromede Maroteaux-Lamy y se evalúan sus resultados, indicaciones, seguridad ridad y efectos adversos. Se examina el valor actual del TPH en estasenfermedades y más específicamente en el síndrome de Hurler,síndrome de Maroteaux-Lamy, leucodistrofia de células globoides,leucodistrofia metacromática y enfermedad de Gaucher. Se comunicanlos resultados iniciales obtenidos con TRS, TME y con terapia génica.Conclusiones. Se han producido grandes avances en el tratamientode algunas enfermedades lisosomales en las últimas décadasgracias a un uso juicioso del TPH y la TRE y se abren nuevas perspectivascon la aplicación de novedosos instrumentos terapéuticoscomo la TRS y la TME

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-celltransplants (HST) and enzyme replacement therapy (ERT), the new therapeutic strategies with small molecules such assubstrate 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. Theiroutcomes, indications, safety and side effects are also evaluated. We examine the value of HST in these diseases and moreparticularly in Hurler syndrome, Maroteaux-Lamy syndrome, globoid cell leukodystrophy, metachromatic leukodystrophyand Gaucher disease. The initial results from using SRT, EET and with gene therapy are briefly outlined. Conclusions. Agreat deal of progress has been made in the treatment of some lysosomal diseases in recent decades due to careful use of HSTand ERT. Furthermore, the application of the latest therapeutic instruments such as SRT and EET opens up new perspectivesin this field

[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.

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

Introducción. El síndrome de hemiconvulsión-hemiplejía (HH) se caracteriza por crisis hemiclónicas prolongadas seguidas de hemiplejía muchas veces permanente. Se presentan dos pacientes con síndrome HH y se discute el valor de la neuroimagen en el diagnóstico, con inclusión de la resonancia magnética (RM) cerebral en secuencias potenciadas en difusión, y su evolución clinicorradiológica. Casos clínicos. Caso 1: niña de 16 meses que ingresa por presentar crisis hemiclónica derecha, febril, de al menos 30 minutos de duración, y hemiparesia derecha persistente. Tomografía computarizada (TC) craneal inicial, normal. RM cerebral a los 3 días: secuencias potenciadas en T2 normales; secuencias potenciadas en difusión, con disminución de difusión en región temporoparietooccipital del hemisferio izquierdo. TC craneal a los 6 meses: hemiatrofia cerebral izquierda. A los 4 años y 8 meses persiste paresia de la mano derecha; no ha vuelto a presentar crisis y su desarrollo psíquico es normal. Caso 2: niña de 2 años y 6 meses que ingresa en la Unidad de Cuidados Intensivos Pediátricos por crisis hemiclónica derecha, febril, de 35-40 minutos de duración, con hemiplejía derecha persistente. Antecedente de retraso psicomotor secundario a cromosomopatía, con TC craneal normal. TC a las 48 horas del episodio: edema de hemisferio cerebral izquierdo. RM cerebral a los 7 días de su ingreso: en secuencias potenciadas en T2 y en secuencias potenciadas en difusión se aprecia una afectación extensa del hemisferio cerebral izquierdo. TC a los 3 meses: hemiatrofia cerebral izquierda. A los 5 años y 4 meses persiste hemiparesia; no ha vuelto a presentar crisis y recibe educación especializada. Conclusión. Aunque raro en nuestro medio, es posible observar síndrome HH en el contexto de estados febriles hemiclónicos. La RM cerebral en secuencias potenciadas en difusión puede ser el único medio de demostrar la lesión cerebral inicial (AU)

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 (AU)

Toxina botulínica y tratamiento actual de la parálisis cerebral infantil / Botulinic toxin and present treatment of child cerebral palsy

La parálisis cerebral constituye una causa frecuente de discapacidad en la infancia. La espasticidad, presente en cerca del 80 por ciento de los casos, es una de las principales causas de trastorno funcional en estos pacientes. Además, predispone al desarrollo de contracturas articulares, lo que puede producir un deterioro aún mayor. La toxina botulínica ha demostrado ser eficaz para tratar la espasticidad. Parece ser una alternativa útil para el tratamiento del pie equino espástico en pacientes con parálisis cerebral que conservan la capacidad para la marcha y podría tener, además, otras indicaciones. Sin embargo, hay algunas cuestiones que permanecen sin esclarecer, sobre todo relacionadas con grupos musculares concretos y con la interpretación de los resultados, lo que sin duda hace necesario continuar la investigación (AU)

[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.

[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.

[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.

[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.