[Classification of idiopathic generalised epilepsies in patients over 16 years of age]. / Clasificacion de las epilepsias generalizadas idiopaticas en mayores de 16 años.

INTRODUCTION: Idiopathic generalised epilepsies (IGE) are a set of electroclinical syndromes with different phenotypes. Our aim is to analyse those phenotypes in patients over 16 years of age. PATIENTS AND METHODS: We conducted a retrospective analysis of a series of patients with IGE. They were classified as childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), epilepsy with tonic-clonic seizures only (TCSE), epilepsy with eyelid myoclonias and absences (EMA) and pure photogenic epilepsy (PE). RESULTS: We included 308 patients, the majority females (56.8%), in our study. JME was the most prevalent (40.9%), followed by TCSE (30%), JAE (10%), EMA (8.7%), CAE (7.7%) and PE (1.6%). The types of seizures presented by the most patients were tonic-clonic (89.6%), myoclonic (45.4%), absence (31.4%), reflex seizures (13.3%), eyelid myoclonias (12.6%), non-epileptic psychogenic seizures (3.6%) and status epilepticus (1.9%). They all had generalised spike-and-wave discharges in the electroencephalogram (EEG). 19.2% presented asymmetrical discharges and 28.2% showed a photoparoxysmal response. We observed differences between syndromes in polytherapy (p < 0.0001), withdrawal of therapy (p = 0.01) and being seizure-free beyond the age of 50 (p = 0.004). CONCLUSIONS: JME was the most frequent. Generalised tonic-clonic seizures were the type of seizures presented by the most patients, followed by myoclonic, absent and reflex seizures. The EEG showed a photoparoxysmal response in over a quarter of the patients, and one in five displayed asymmetrical anomalies. Differences were observed according to the syndrome in polytherapy, persistence of seizures and withdrawal of treatment.

TITLE: Clasificacion de las epilepsias generalizadas idiopaticas en mayores de 16 años.Introduccion. Las epilepsias generalizadas idiopaticas (EGI) son un conjunto de sindromes electroclinicos con distintos fenotipos. Nuestro objetivo es analizar dichos fenotipos en pacientes mayores de 16 años. Pacientes y metodos. Analizamos retrospectivamente una serie de pacientes con EGI. Los clasificamos en epilepsia de ausencias infantil (EAI), epilepsia de ausencias juvenil (EAJ), epilepsia mioclonica juvenil (EMJ), epilepsia con crisis tonicoclonicas solo (ECTC), epilepsia con ausencias y mioclonias palpebrales (EAM) y epilepsia fotogenica pura (EF). Resultados. Incluimos 308 pacientes, mayoritariamente mujeres (56,8%). La EMJ fue mas prevalente (40,9%), seguida de la ECTC (30%), la EAJ (10%), la EAM (8,7%), la EAI (7,7%) y la EF (1,6%). Los tipos de crisis que presentaron mas pacientes fueron las tonicoclonicas (89,6%), las mioclonicas (45,4%), las ausencias (31,4%), las crisis reflejas (13,3%), las mioclonias palpebrales (12,6%), las crisis psicogenas no epilepticas (3,6%) y el estado epileptico (1,9%). Todos tenian descargas punta-onda generalizada en el electroencefalograma (EEG). El 19,2% presento descargas asimetricas y el 28,2%, respuesta fotoparoxistica. Observamos diferencias entre sindromes en politerapia (p < 0,0001), retirada de tratamiento (p = 0,01) y estar libres de crisis por encima de los 50 años (p = 0,004). Conclusiones. La EMJ fue la EGI mas frecuente. Las crisis tonicoclonicas generalizadas fueron el tipo de crisis que presentaron mas pacientes, seguidas de las mioclonicas, las ausencias y las crisis reflejas. El EEG mostro en mas de una cuarta parte de los pacientes una respuesta fotoparoxistica, y en uno de cada cinco, anomalias asimetricas. Se observaron diferencias segun el sindrome en politerapia, persistencia de crisis y retirada de tratamiento.

[Use of benzodiazepines in prolonged seizures and status epilepticus in the community]. / Uso benzodiacepinas en crisis prolongadas y estado epiléptico en la comunidad.

Prolonged seizures and status epilepticus are common neurological medical emergencies. Early and appropriate treatment is essential to reduce morbidity and mortality. Most seizures occur in the community, so parents and caregivers must be prepared for their management. Benzodiazepines (BZD) are the first-line drugs used, with rectal diazepam (DZPr) being the most commonly used in pre-hospital treatment in Spain. In September 2011, the European Medicines Agency (EMA) authorized the use of oromucosal midazolam (MDZb) for the treatment of prolonged acute convulsive seizures in patients aged 3 months to <18 years. MDZb has a rapid onset, short duration of effect, and avoids first-pass hepatic metabolism. MDZb has shown to be at least as or more effective than DZPr to stop the seizures. Buccal administration is easier and more socially accepted, especially in adolescents and adults. It is a safe drug with similar effects to other BZD; MDZb improves the overall cost-effectiveness of seizures management.

Uso benzodiacepinas en crisis prolongadas y estado epiléptico en la comunidad / Use of benzodiazepines in prolonged seizures and status epilepticus in the community

Las crisis prolongadas y el estado epiléptico son emergencias médicas neurológicas frecuentes y su tratamiento adecuado y precoz es fundamental para reducir su morbi-mortalidad. La mayoría de las crisis se inician en un medio extrahospitalario, lo que obliga a familiares y cuidadores a estar preparados en las medidas de actuación iniciales ante una crisis convulsiva. En su manejo, las benzodiacepinas (BZD) son los fármacos de primera línea, siendo el uso de diazepam rectal (DZPr) el más extendido en el ámbito prehospitalario en España. La Agencia Europea del Medicamento (EMA) autorizó en septiembre del 2011 el empleo de midazolam bucal (MDZb) para el manejo de las crisis epilépticas repetidas en pacientes entre los 3 meses y 18 años. Es un fármaco de acción rápida por evitar la metabolización hepática y con efecto de corta duración. MDZb ha demostrado al menos igual o mayor eficacia que el DZPr y la vía de administración bucal es más sencilla y mejor aceptada socialmente, sobre todo en adolescentes y adultos. Es un fármaco seguro, con efectos adversos similares a otras BZD. Estudios de farmacoeconomía demuestran un buen coste-efectividad global en el manejo de las crisis frente al DZPr, reduciendo traslados en ambulancia e ingresos hospitalarios

Prolonged seizures and status epilepticus are common neurological medical emergencies. Early and appropriate treatment is essential to reduce morbidity and mortality. Most seizures occur in the community, so parents and caregivers must be prepared for their management. Benzodiazepines (BZD) are the first-line drugs used, with rectal diazepam (DZPr) being the most commonly used in pre-hospital treatment in Spain. In September 2011, the European Medicines Agency (EMA) authorized the use of oromucosal midazolam (MDZb) for the treatment of prolonged acute convulsive seizures in patients aged 3 months to < 18 years. MDZb has a rapid onset, short duration of effect, and avoids first-pass hepatic metabolism. MDZb has shown to be at least as or more effective than DZPr to stop the seizures. Buccal administration is easier and more socially accepted, especially in adolescents and adults. It is a safe drug with similar effects to other BZD; MDZb improves the overall cost-effectiveness of seizures management

Manejo de la crisis convulsiva prolongada en la comunidad: resultados del estudio PERFECT en España / Management of prolonged convulsive seizures in the community: Results of the PERFECT™ study in Spain

INTRODUCCIÓN: La Iniciativa Practices in Emergency and Rescue medication For Epilepsy managed with Community administered Therapy (PERFECT(TM)) se inició en 2011 con el objetivo de conocer mejor cómo se tratan las crisis convulsivas prolongadas y cómo se administra la medicación de rescate en la comunidad en Europa. Este artículo analiza sus resultados iniciales en España. MATERIAL Y MÉTODOS: Revisión de las guías clínicas, guías para colegios y marco legal relevante sobre el tratamiento de las crisis convulsivas prolongadas y una encuesta a 20 profesionales sanitarios que tratan a niños con crisis convulsivas prolongadas en España. RESULTADOS: Las guías clínicas existentes abordan principalmente el ámbito hospitalario y contienen poca información sobre cómo deben tratarse las crisis convulsivas prolongadas en la comunidad. Las recomendaciones para los colegios no son claras respecto a si los profesores, que no tienen la obligación legal de administrar la medicación de rescate a los niños que tienen a su cargo, pueden o deben administrarla. Esta incertidumbre determina que la administración de medicación de rescate al niño con una crisis convulsiva prolongada durante el horario escolar dependa los recursos y de la formación disponibles en cada colegio. CONCLUSIONES: Es necesario contar con guías explícitas que aborden los ámbitos educativo y sanitario, información más clara para padres y colegios, y formación más sistemática a disposición de los cuidadores. Ello facilitará que todos los niños con riesgo de presentar crisis convulsivas prolongadas reciban el tratamiento de rescate apropiado, independientemente del lugar en el que ocurra la crisis

INTRODUCTION: The Practices in Emergency and Rescue medication For Epilepsy managed with Community administered Therapy (PERFECT(TM)) Initiative was set up in 2011 to gain a better understanding of how prolonged convulsive seizures are managed, and rescue medication is administered, in out-of-hospital settings across Europe. This paper explores the initial research findings for Spain. MATERIAL AND METHODS: A review was made of existing clinical guidelines, guidance to schools, and relevant policy and legal frameworks, as well as a survey of 20 healthcare professionals who treat children with prolonged convulsive seizures in Spain. RESULTS: Existing clinical guidelines pertain mainly to the hospital setting, and contain very little information on how prolonged seizures should be managed outside of the hospital. Guidance for schools is unclear as to whether teachers are allowed to administer rescue medication to children, and there is no legal obligation for school staff to administer medication to children under their care. As a result of such uncertainty, whether or not children who experience prolonged seizures receive their rescue medication during school hours depends mostly on the resources and training available in each school. CONCLUSIONS: There is a need for more explicit guidance covering educational and healthcare settings, clearer information to parents and schools, and more systematic training to be made available to caregivers. This is to ensure that all children at risk of a prolonged convulsive seizure receive rescue medication in a timely manner, regardless of where their seizure occurs

[Management of prolonged convulsive seizures in the community: results of the PERFECT™ study in Spain]. / Manejo de la crisis convulsiva prolongada en la comunidad: resultados del estudio PERFECT en España.

INTRODUCTION: The Practices in Emergency and Rescue medication For Epilepsy managed with Community administered Therapy (PERFECT™) Initiative was set up in 2011 to gain a better understanding of how prolonged convulsive seizures are managed, and rescue medication is administered, in out-of-hospital settings across Europe. This paper explores the initial research findings for Spain. MATERIAL AND METHODS: A review was made of existing clinical guidelines, guidance to schools, and relevant policy and legal frameworks, as well as a survey of 20 healthcare professionals who treat children with prolonged convulsive seizures in Spain. RESULTS: Existing clinical guidelines pertain mainly to the hospital setting, and contain very little information on how prolonged seizures should be managed outside of the hospital. Guidance for schools is unclear as to whether teachers are allowed to administer rescue medication to children, and there is no legal obligation for school staff to administer medication to children under their care. As a result of such uncertainty, whether or not children who experience prolonged seizures receive their rescue medication during school hours depends mostly on the resources and training available in each school. CONCLUSIONS: There is a need for more explicit guidance covering educational and healthcare settings, clearer information to parents and schools, and more systematic training to be made available to caregivers. This is to ensure that all children at risk of a prolonged convulsive seizure receive rescue medication in a timely manner, regardless of where their seizure occurs.

La Neurología Pediátrica y las enfermedades minoritarias / Pediatric Neurology and rare diseases

El Servicio de Neurología Pediátrica del Hospital Universitario Vall d´Hebrond e Barcelona, en sus 30 años de historia, ha sido pionero en el desarrollo de asitencia e investigación en enfermedades neurológicas graves que afectan als istema nervioso en desarrollo. Sobre la base de un enfoque propio del hospital terciario, ha dadoprioridad a la interdisciplinariedad en la asistencia y a la potenciación de investigación y docencia a través de la creción de un grupo propio de investigación y un progrma de máster en Neurología Pediátrica. La presente revisión ilustra la trayectoria del servicio a tráves de sus contribuciones en el campo de las enfermedades minoritarias. Entre la extensa bibliografía del grupo, destaca la descripción o caracterización de al menos tres nuevos síndromes neurológicos pediátricos, la leuconcefalopatía maligna con hiperglicinemia e hipertensión pulmonar, el síndorme de disgenesia congénita trocoencefálica y una nueva variante de encefalopatía epiléptica, así como la productiva investigación en neurogenética de la migraña y otros trastornos paroxísticos y en la fisiopatología de la necrosis-regeneración muscular asociada al déficit de distrofina (AU)

Over the last three decades, The Pediatric Neurology Sevice at Vall d´Hebron University Hospital in Barcelona has been a pioneer in the country in developing a modern approach to the care of the severe neurological disorders of the developing nervous system. In the setting of a tertiary care enter, a multidisciplinar attentionto the patient, the fostering of clinical and applied research and the excellence in postgraduate training have been prioritized. This is reflected in the foudation of a laboratory research group and a Master programme in Pediatric Neurology. In the present review the Service achievements are illustrated through a brief accout of the contributions made in the field of rare disorders. Among a large number of publications, we emphasize the description and characterization of at least three novel syndromes, a progressive vacuolating glycine leukoencephalopathy with pulmonary hypertension, congenital brainstem dysgenesis and a distinct epileptic encephalopathy phenotype, as well as a rather productive research in genetics of migraine and other paroxysmal disorders and in the pathophysiology of muscle necrosis and regeneration associated to dystrophin deficiency (AU)

[Private mutations in the myophosphorylase gene: the first case in a patient of Latin American descent]. / Mutaciones privadas en el gen de la miofosforilasa: primer caso en un paciente de origen latinoamericano.

INTRODUCTION: McArdle's disease (glycogenoses type V) is a common metabolic myopathy caused by deficient myophosphorylase activity. The disease is due to mutations in the myophosphorylase (PYGM) gene and is present in a large number of countries. CASE REPORT: A 13-year-old male who suffered an episode of muscle pain and offered increased levels of creatinkinase in plasma, myoglobinuria and mild weakness of the proximal muscles, after short but vigorous exercise. The patient was born in Ecuador and was adopted by a Spanish family. The myophosphorylase gene was analysed completely and the patient was found to be a carrier of a missense mutation, a homozygous change where a G is replaced by an A in exon 11, changing a valine for a methionine in codon 456 (V456M). The mutation described above affects an amino acid that is conserved in the enzyme and which was not present in the control population that was studied. CONCLUSIONS: These findings show the presence of McArdle's disease in several ethnic groups and confirm that the ethnic origin of the patient is important when it comes to deciding what mutations should be analysed first in molecular diagnosis studies.

Mutaciones privadas en el gen de la miofosforilasa: primer caso en un paciente de origen latinoamericano / Private mutations in the myophosphorylase gene: The first case in a patient of latin american descent

La enfermedad de McArdle (glicogenosis tipo V) es una miopatía metabólica común causada por unadeficiencia de la actividad de la miofosforilasa. La enfermedad se debe a mutaciones en el gen de la miofosforilasa (PYGM) y está presente en un gran número de países. Caso clínico. Varón de 13 años de edad que sufrió un episodio de dolor muscular y presentó unos niveles elevados de creatincinasa en plasma, mioglobinuria y debilidad de la musculatura proximal moderada, después de un corto pero vigoroso ejercicio. El paciente nació en Ecuador y fue adoptado por una familia española.Se analizó completamente el gen de la miofosforilasa y se encontró que el paciente era portador de una mutación consistente en pérdida de sentido, un cambio homocigótico de una G por una A en el exón 11, cambiando una valina por una metionina en el codón 456 (V456M). La mutación previamente descrita afecta a un aminoácido conservado en la enzima y no estaba presenteen la población control estudiada. Conclusiones. Estos hallazgos demuestran la presencia de la enfermedad de McArdle en varios grupos étnicos y sugiere que el origen étnico del paciente es importante para decidir qué mutaciones deberían analizarse primero en los estudios diagnósticos moleculares (AU)

McArdle's disease (glycogenoses type V) is a common metabolic myopathy caused by deficientmyophosphorylase activity. The disease is due to mutations in the myophosphorylase (PYGM) gene and is present in a large number of countries. Case report. A 13-year-old male who suffered an episode of muscle pain and offered increased levels of creatinkinase in plasma, myoglobinuria and mild weakness of the proximal muscles, after short but vigorous exercise. The patient was born in Ecuador and was adopted by a Spanish family. The myophosphorylase gene was analysed completely andthe patient was found to be a carrier of a missense mutation, a homozygous change where a G is replaced by an A in exon 11, changing a valine for a methionine in codon 456 (V456M). The mutation described above affects an amino acid that is conserved in the enzyme and which was not present in the control population that was studied. Conclusions. These findings show thepresence of McArdle’s disease in several ethnic groups and confirm that the ethnic origin of the patient is important when it comes to deciding what mutations should be analysed first in molecular diagnosis studies (AU)

Crisis gelásticas y astrocitoma hipotalámico de bajo grado / Gelastic seizures and low-grade hypothalamic astrocytoma

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[Cerebellar atrophy following acute Mycoplasma pneumoniae cerebellitis]. / Atrofia cerebelosa secundaria a cerebelitis aguda por Mycoplasma pneumoniae.

INTRODUCTION: Acute cerebellitis is an uncommon complication following Mycoplasma pneumoniae infection. A benign and self-limited course has been described in the few reports found of this association. CASE REPORTS: We report two patients with an apparently M. pneumoniae-induced acute cerebellitis that resulted in cerebellar atrophy. Patients presented with a cerebellar syndrome including ataxia, hypotonia, dysarthric speech and dysmetria, which were preceded by signs of respiratory infection. Initial brain magnetic resonance imaging (MRI) in case 1 was normal but in case 2 it displayed striking cerebellar swelling, small fourth ventricle and supratentorial ventriculomegaly which was self-limited and did not require neurosurgical intervention. Serological studies confirmed a recent M. pneumoniae infection. Case 1 has followed an unfavourable clinical course, with incomplete resolution of cerebellar dysfunction, while case 2 has remained asymptomatic. Follow-up brain MRI have demonstrated prominent cerebellar atrophy in both patients. CONCLUSIONS: M. pneumoniae infection should be considered in those patients with acute cerebellitis showing an incomplete resolution of cerebellar dysfunction or those who develop early cerebellar atrophy. The presenting MRI findings do not seem to predict final neurological outcome.

Atrofia cerebelosa secundaria a cerebelitis aguda por Mycoplasma pneumoniae / Cerebellar atrophy following acute mycoplasma pneumoniae cerebellitis

Introducción. La cerebelitis aguda es una complicación infrecuente de la infección por Mycoplasma pneumoniae. Los pocos pacientes descritos han seguido un curso benigno y autolimitado de forma similar al de las cerebelitis relacionadas con otros gérmenes. Casos clínicos. Describimos dos pacientes con una cerebelitisaguda por M. pneumoniae que evoluciona en pocos meses hacia una marcada atrofia cerebelosa. Los pacientes presentaron un síndrome cerebeloso caracterizado por ataxia, hipotonía, disartria y dismetría de las cuatro extremidades, precedido por signos de infección respiratoria. La resonancia magnética (RM) cerebral practicada durante la fase aguda en el caso 1 resultó normal y e nel caso 2 demostró un llamativo edema del parénquima cerebeloso, con IV ventrículo pequeño y ventriculomegalia supratentorial, que se autolimitó y que no requirió de intervención neuroquirúrgica. Los estudios serológicos permitieron confirmar la infección reciente por M. pneumoniae. En el caso 1 se ha observado la persistencia de signos de disfunción cerebelosa, mientras que el caso 2 está asintomático. Ambos pacientes muestran una llamativa atrofia cerebelosa en las RM cerebrales practicadas a lo largo de su control clínico. Conclusiones. Debe considerarse la infección por M. pneumoniae en pacientes con cerebelitis aguda que presenten resolución incompleta de la disfunción cerebelosa o que evolucionen de forma precoz hacia la atrofia cerebelosa. Las manifestaciones neurorradiológicas iniciales no permiten predecir el pronóstico neurológico final (AU)

Introduction. Acute cerebellitis is an uncommon complication following Mycoplasma pneumoniae infection. A benign and self-limited course has been described in the few reports found of this association. Case reports. We report twopatients with an apparently M. pneumoniae-induced acute cerebellitis that resulted in cerebellar atrophy. Patients presented with a cerebellar syndrome including ataxia, hypotonia, dysarthric speech and dysmetria, which were preceded by signs of respiratory infection. Initial brain magnetic resonance imaging (MRI) in case 1 was normal but in case 2 it displayed striking cerebellar swelling, small fourth ventricle and supratentorial ventriculomegaly which was self-limited and did not requiren euro surgical intervention. Serological studies confirmed a recent M. pneumoniae infection. Case 1 has followed an unfavourable clinical course, with incomplete resolution of cerebellar dysfunction, while case 2 has remained asymptomatic. Follow-up brain MRI have demonstrated prominent cerebellar atrophy in both patients. Conclusions. M. pneumoniae infection should be considered in those patients with acute cerebellitis showing an incomplete resolution of cerebellar dysfunction or those who develop early cerebellar atrophy. The presenting MRI findings do not seem to predict final neurological outcome (AU)

[Subacute sclerosing panencephalitis: combined treatment with interferon alpha and intraventricular ribavirin]. / Panencefalitis esclerosante subaguda: tratamiento combinado con interferón alfa y ribavirina intraventricular.

INTRODUCTION: Subacute sclerosing panencephalitis (SSPE) is a chronic neurodegenerative disease secondary to an infection of the central nervous system by the measles virus, with no effective treatment. The introduction of therapy with intraventricular interferon alpha (IFN-alpha) and its later association with ribavirin aroused new expectations. In experimental studies the two drugs were seen to exert a synergic effect in reducing viral replication. Therapeutic studies carried out in patients with SSPE with the two pharmaceuticals have offered contradictory findings. CASE REPORTS: We present the cases of two patients with an early-onset, fast progressing form of SSPE, who were treated with a combined regime of oral isoprenosin, intraventricular IFN-alpha and ribavirin, which was administered intravenously in one case and intraventricularly in the other. At the beginning of treatment the patients' deterioration stabilised briefly and temporarily, but then renewed its progress. CONCLUSIONS: Combined therapy with intraventricular IFN-alpha and ribavirin was not effective in our patients. The late onset and rapidly progressing symptoms of the disease may have had an effect on the poor results obtained.

Panencefalitis esclerosante subaguda: tratamiento combinado con interferon alfa y ribavirina intraventricular / Subacute sclerosing panencephalitis: combined treatment with interferon alpha and intraventricular ribavirin

Introducción. La panencefalitis esclerosante subaguda (PEES) es una enfermedad neurodegenerativa crónica secundaria a una infección del sistema nervioso central por el virus del sarampión, sin un tratamiento efectivo. La introducción del tratamiento con interferón alfa (IFN-a) intraventricular y la asociación posterior de ribavirina despertó nuevas expectativas. En estudios experimentales se comprobó un efecto sinérgico de ambos fármacos en la disminución de la replicación vírica. Los estudios terapéuticos realizados en pacientes afectos de PEES con ambos fármacos han dado resultados discordantes. Casos clínicos. Presentamos dos pacientes afectos de PEES con una forma de inicio precoz y rápidamente progresiva, que se trataron con una pauta combinada de isoprenosina oral, IFN-a intraventricular y ribavirina endovenosa en un caso, e intraventricular, en el otro. Al inicio del tratamiento. los pacientes presentaron una estabilización temporal breve de su deterioro, para después progresar de nuevo. Conclusión. El tratamiento combinado con IFN-a intraventricular y ribavirina no ha sido efectivo en nuestros pacientes. Es posible que su inicio tardío y la forma de presentación rápidamente progresiva de la enfermedad hayan influido en los malos resultados (AU)

Introduction. Subacute sclerosing panencephalitis (SSPE) is a chronic neurodegenerative disease secondary to an infection of the central nervous system by the measles virus, with no effective treatment. The introduction of therapy with intraventricular interferon alpha (IFN-α) and its later association with ribavirin aroused new expectations. In experimental studies the two drugs were seen to exert a synergic effect in reducing viral replication. Therapeutic studies carried out in patients with SSPE with the two pharmaceuticals have offered contradictory findings. Case reports. We present the cases of two patients with an early-onset, fast progressing form of SSPE, who were treated with a combined regime of oral isoprenosin, intraventricular IFN-α and ribavirin, which was administered intravenously in one case and intraventricularly in the other. At the beginning of treatment the patients’ deterioration stabilised briefly and temporarily, but then renewed its progress. Conclusions. Combined therapy with intraventricular IFN-α and ribavirin was not effective in our patients. The late onset and rapidly progressing symptoms of the disease may have had an effect on the poor results obtained (AU)

Epilepsia y alteración del pelo en un lactante / Epilepsy and hair alterations in a neonate

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[Congenital insensitivity to pain with anhidrosis associated with congenital myasthenic syndrome]. / Insensibilidad congénita al dolor con anhidrosis asociada a síndrome miasténico congénito.

INTRODUCTION: Congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV (HSAN IV) is a rare autosomal recessive disorder featuring recurrent fever episodes, inability to sweat, absent response to noxious stimuli, self mutilating behavior and mental retardation. It has been associated with mutations in the NTRK1 gene, located in 1q21-22 and encoding a high-affinity NGF receptor. CASE REPORT: An 8-year-old boy, the first son of consanguineous parents, presented with hypotonia, episodic hyperpyrexia and global developmental delay since the neonatal period. In addition to these signs, typical of CIPA, he displayed some other not previously described in this disease, such as facial dysmorphism, a severe swallowing disorder and a myogenic EMG pattern, that led to the initial suspicion of a muscle disorder. Molecular genetics studies uncovered a mutation c.C2011T in exon 15 of the NTRK1 gene. Genetic counselling was possible in the following pregnancy of the couple, where the female fetus was found to harbour the mutation in heterozygosity. The subsequent diagnosis of a congenital myasthenic syndrome in this sister led to neurophysiological re-evaluation of the probandus, in whom a myasthenic pattern of muscle activation was also found. CONCLUSIONS: A patient with CIPA and congenital myasthenic syndrome is described. CIPA must be the first diagnostic hypothesis when assessing a patient with insensitivity to pain, anhidrosis and self-mutilation. Given the rather homogeneous presentation of CIPA, the occurrence of atypical myopathic manifestations should raise the suspicion of a concurrent disorder. The present consanguineous kindred illustrates a rare instance of transmission of two mutated alleles giving rise to two unrelated, infrequent neurological syndromes.

Insensibilidad congénita al dolor con anhidrosis asociada a síndrome miasténico congénito / Congenital insensitivity to pain with anhidrosis associated with congenital myasthenic syndrome

Introducción. La insensibilidad congénita al dolor con anhidrosis (CIPA) o neuropatía hereditaria sensitivoautonómica de tipo IV (HSAN IV) es un raro trastorno autosómico recesivo caracterizado por episodios recurrentes de fiebre, anhidrosis, ausencia de sensibilidad al dolor y retraso mental de gravedad variable. Se asocia a mutaciones en el gen NTRK1, localizado en el cromosoma 1q21-22, que codifica uno de los receptores del factor de crecimiento nervioso. Caso clínico. Describimos el caso de un niño de 8 años de edad, primer hijo de padres consanguíneos, que presenta hipotonía, episodios de hiperpirexia y retraso global desde el período neonatal, manifestaciones típicas de la CIPA, además de signos previamente no descritos en esta enfermedad como son anomalías fenotípicas, un grave trastorno de deglución durante los primeros meses de vida y un patrón miógeno en el estudio neurofisiológico, que condujeron a la sospecha inicial de proceso miopático. El estudio genético molecular detectó una mutación c.C2011T en el exón 15 del gen NTRK1. El hallazgo de dicha mutación en heterocigosidad en la hermana menor del paciente permitió efectuar consejo genético. Sin embargo, el diagnóstico de un síndrome miasténico congénito en esta hermana y la posterior observación de hallazgos neurofisiológicos miasteniformes también en nuestro paciente permiten explicar la existencia de estas manifestaciones atípicas de la CIPA. Conclusiones. Presentamos un paciente afecto de CIPA y síndrome miasténico congénito. Debe considerarse la posibilidad de CIPA como primera hipótesis diagnóstica en la valoración de un paciente con insensibilidad al dolor, anhidrosis y automutilación. Dada la considerable homogeneidad clínica de la CIPA, la aparición de signos atípicos miopáticos debe despertar la sospecha de algún otro trastorno asociado. La familia consanguínea que presentamos ilustra la situación muy poco frecuente de transmisión de dos alelos mutados, causantes de dos enfermedades neurológicas supuestamente monogénicas, a un mismo individuo (AU)

Introduction. Congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV (HSAN IV) is a rare autosomal recessive disorder featuring recurrent fever episodes, inability to sweat, absent response to noxious stimuli, self mutilating behavior and mental retardation. It has been associated with mutations in the NTRK1 gene, located in 1q21-22 and encoding a high-affinity NGF receptor. Case report. An 8-year-old boy, the first son of consanguineous parents, presented with hypotonia, episodic hyperpyrexia and global developmental delay since the neonatal period. In addition to these signs, typical of CIPA, he displayed some other not previously described in this disease, such as facial dysmorphism, a severe swallowing disorder and a myogenic EMG pattern, that led to the initial suspicion of a muscle disorder. Molecular genetics studies uncovered a mutation c.C2011T in exon 15 of the NTRK1 gene. Genetic counselling was possible in the following pregnancy of the couple, where the female fetus was found to harbour the mutation in heterozygosity. The subsequent diagnosis of a congenital myasthenic syndrome in this sister led to neurophysiological re-evaluation of the probandus, in whom a myasthenic pattern of muscle activation was also found. Conclusions. A patient with CIPA and congenital myasthenic syndrome is described. CIPA must be the first diagnostic hypothesis when assessing a patient with insensitivity to pain, anhidrosis and selfmutilation. Given the rather homogeneous presentation of CIPA, the occurrence of atypical myopathic manifestations should raise the suspicion of a concurrent disorder. The present consanguineous kindred illustrates a rare instance of transmission of two mutated alleles giving rise to two unrelated, infrequent neurological syndromes (AU)

[A patient with bilateral lesion in the striatum and slowly progressive dystonia secondary to T14487C mutation in the ND6 gene of complex I of the mitochondrial respiratory chain]. / Paciente con lesión bilateral del estriado y distonía lentamente progresiva secundarias a la mutación T14487C en el gen ND6 del complejo I de la cadena respiratoria mitocondrial.

INTRODUCTION: A large number of diseases present as bilateral striatal lesion syndrome (BSLS). Clinical manifestations, course and prognosis of these diseases are extremely variable. On the basis of their evolutive course, they can be separated into two major groups: acute, which include toxic, infectious or parainfectious causes, and subacute or chronic, in which inborn errors of metabolism, especially mitochondrial disorders, are the main causes. CASE REPORT: We report a detailed clinical follow-up of a 18 years old Caucasian male who, at the age of four, presented with BSLS. A respiratory chain defect was suspected on the basis of slowly progressive dystonia and cognitive impairment, changes in serial MRI studies, and the finding of 'trabecular fibers' as well as a 50% decrease of the complex I activity in striated-skeletal muscle specimen. Blood, urine and CSF markers classically associated with respiratory chain diseases were normal. Molecular studies identified a new pathogenetic mutation (T14487C) in the mitochondrial ND6 gene of the respiratory chain complex I. CONCLUSION: Mitochondrial metabolism disorders should be ruled out in patients presenting with a subacute or chronic form of BSLS even in the absence of other common mitochondrial disease markers.

Paciente con lesión bilateral del estriado y distonía lentamente progresiva secundarias a la mutación T14487C en el gen ND6 del complejo I de la cadena respiratoria mitocondrial / A patient with bilateral lesión in the striatum and slowly progressive dystonia secondary to T14487C mutation in the ND6 gene of complex I

Introducción. El síndrome de lesión bilateral del estriado (SLBE) constituye la forma de presentación de un elevado número de enfermedades. Las manifestaciones clínicas, la evolución y el pronóstico de las mismas es muy variable. En función de su curso evolutivo, éstas pueden dividirse en dos grandes grupos: unas, de presentación aguda, que suelen responder a causas tóxicas, infecciosas o parainfecciosas, y otras, subagudas o crónicas, cuya causa fundamental son los errores congénitos del metabolismo. Caso clí- nico. Varón de 18 años que, a los 4 años de edad, debutó con un SLBE. Se sospechó un defecto de la cadena respiratoria mitocondrial sobre la base de la distonía y la alteración de las funciones cognitivas lentamente progresiva, la evolución de las imágenes en la resonancia magnética cerebral y el hallazgo de fibras trabeculadas, así como una disminución del 50% en la actividad del complejo I en el músculo estriado. Sin embargo, las determinaciones bioquímicas en la sangre, la orina y el líquido cefalorraquídeo, encaminadas a detectar trastornos en la función mitocondrial, fueron repetidamente normales. Los estudios moleculares identificaron una nueva mutación patogenética (T14487C) del gen mitocondrial ND6 del complejo I de la cadena respiratoria mitocondrial. Conclusiones. Deben descartarse trastornos del metabolismo mitocondrial cuando se valoren pacientes afectados de un SLBE de curso clínico cronicorrecurrente, incluso en ausencia de otros marcadores que así lo sugieran (AU)

Introduction. A large number of diseases present as bilateral striatal lesion syndrome (BSLS). Clinical manifestations, course and prognosis of these diseases are extremely variable. On the basis of their evolutive course, they can be separated into two major groups: acute, which include toxic, infectious or parainfectious causes, and subacute or chronic, in which inborn errors of metabolism, especially mitochondrial disorders, are the main causes. Case report. We report a detailed clinical follow-up of a 18 years old Caucasian male who, at the age of four, presented with BSLS. A respiratory chain defect was suspected on the basis of slowly progressive dystonia and cognitive impairment, changes in serial MRI studies, and the finding of ‘trabecular fibers’ as well as a 50% decrease of the complex I activity in striatedskeletal muscle specimen. Blood, urine and CSF markers classically associated with respiratory chain diseases were normal. Molecular studies identified a new pathogenetic mutation (T14487C) in the mitochondrial ND6 gene of the respiratory chain complex I. Conclusion. Mitochondrial metabolism disorders should be ruled out in patients presenting with a subacute or chronic form of BSLS even in the absence of other-common mitochondrial disease markers (AU)