Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD syndrome): A case report and literature review. / Síndrome ROHHAD (obesidad de rápida progresión, disfunción hipotalámica, hipoventilación y disregulación autonómica). Presentación de un caso y revisión de la literatura.

INTRODUCTION: ROHHAD syndrome (rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation) is a rare and complex disease, presenting in previously healthy children at the age of 2-4 years. Up to 40% of cases are associated with neural crest tumours. DEVELOPMENT: We present the case of a 2-year-old girl with symptoms of rapidly progressing obesity, who a few months later developed hypothalamic dysfunction with severe electrolyte imbalance, behaviour disorder, hypoventilation, and severe autonomic dysregulation, among other symptoms. Although the pathophysiology of this syndrome remains unclear, an autoimmune hypothesis has been proposed for ROHHAD. Therefore, after obtaining a limited response to intravenous immunoglobulins, we decided to test the response to a high dose cyclophosphamide (low dose was not effective either). Unfortunately our patient experienced many severe complications (among them central pontine myelinolysis, from which the patient recovered, and failure to wean from the ventilator requiring tracheostomy and long term ventilation) that required a prolonged ICU stay. Although her behaviour improved, our patient unfortunately died suddenly at home at the age of 5 due to respiratory pathology. CONCLUSIONS: ROHHAD syndrome is a rare and little-known disease which requires a multidisciplinary approach because it involves complex symptoms and multiple organ system involvement. Alveolar hypoventilation should be identified early and appropriate treatment should be started promptly for the best possible outcome. Immunomodulatory treatment with immunoglobulins, cyclophosphamide, or rituximab has previously resulted in symptom improvement in some cases. Because of the low incidence of the syndrome, multi-centre studies must be carried out in order to gather more accurate information about ROHHAD pathophysiology and design an appropriate therapeutic approach.

Cerebrospinal fluid synaptic proteins as useful biomarkers in tyrosine hydroxylase deficiency.

Tyrosine hydroxylase (TH) deficiency is an inborn error of dopamine biosynthesis and a cause of early parkinsonism. Two clinical phenotypes have been described. Type "B": early onset severe encephalopathy; type "A": later onset, less severe and better response to L-dopa. We aimed to study the expression of several key dopaminergic and gabaergic synaptic proteins in the cerebrospinal fluid (CSF) of a series of patients with TH deficiency and their possible relation with the clinical phenotype and response to L-DOPA. Dopamine transporter (DAT), D2-receptor and vesicular monoamine transporter (VMAT2) were measured in the CSF of 10 subjects with TH deficiency by Western blot analysis. In 3 patients, data of pre- and post-treatment with L-DOPA were available, and in one of them, GABA vesicular transporter was determined. Results were compared to an age-matched control population. The concentration of D2-receptors in CSF was significantly higher in patients with TH deficiency than in controls. Similarly, DAT and vesicular monoamine transporter type 2 were up-regulated. Studies performed before L-DOPA, and on L-DOPA therapy showed a paradoxical response with D2 receptor expression increase as L-Dopa doses and homovanillic concentration gradually raised in a B phenotype patient. The opposite results were found in two patients with A phenotype. However, this is a very small sample, and further studies are needed to conclude robust differences between phenotypes. Synaptic proteins are detectable in the CSF and their quantification can be useful for understanding the pathophysiology of neurotransmitter defects and potentially to adjust and personalize treatments in the future.

Long-term prognosis of childhood absence epilepsy. / Epilepsia ausencia infantil. Pronóstico a largo plazo.

INTRODUCTION: Childhood absence epilepsy (CAE) is considered easily manageable with medication provided that a strict patient classification system is employed. It accounts for 10% of all childhood epilepsy cases starting before the age of 15 and it is most frequent in school-aged girls. The aim of this study is to analyse long-term outcomes of patients diagnosed with CAE according to the Loiseau and Panayiotopoulos criteria and treated during childhood. METHODS: We conducted a retrospective study including 69 patients with CAE who are currently older than 11; data were gathered from medical histories, EEG records, and telephone questionnaires. RESULTS: 52 patients met the Loiseau and Panayiotopoulos criteria. Mean age is now 17.16 years. Female-to-male ratio was 1.65:1; mean age at onset was 6 years and 2 months; mean duration of treatment was 3 years and 9 months. A family history of epilepsy was present in 30.8% of the patients and 7.7% had a personal history of febrile convulsions. Absence seizures were simple in 73.5% of the patients and complex in 26.5%. Response rates to first-line treatment were as follows: valproic acid, 46.3%; and valproic acid plus ethosuximide, 90.9%. The rate of response to second-line therapy (ethosuximide or lamotrigine) was 84.2%; 4% of the patients experienced further seizures after treatment discontinuation, 78.8% achieved seizure remission, and 25% needed psychological and academic support. CONCLUSIONS: Our data show that epileptic patients should be classified according to strict diagnostic criteria since patients with true CAE have an excellent prognosis. The relapse rate was very low in our sample. Despite the favourable prognosis, psychological and academic support is usually necessary.

[Review of 22 patients with 22q11.2 deletion syndrome: phenotype spectrum]. / Revisión de 22 casos de deleción 22q11.2: espectro fenotípico.

INTRODUCTION: The 22q11.2 deletion syndrome is a contiguous gene deletion syndrome with an incidence rate of 1/4,000-6,000 live births. The most specific clinical features are: congenital conotruncal heart diseases, palate anomalies, hypocalcaemia, immunity and learning problems, and a characteristic facial phenotype. The objective of this work is to review the presenting phenotype and clinical features of children with 22q11.2 deletion syndrome as a guide for early diagnosis. PATIENTS AND METHODS: Retrospective study of 22 patients with 22q11.2 deletion syndrome diagnosed at our hospital in the time period 2004-2007. Variables analyzed: incidence, sex, age at diagnosis, presenting phenotype, clinical features, positive family history, mortality and natural history. RESULTS: From a total of 22 patients, 63 % were males, and the median age at diagnosis was of 4.5 years. Presenting pheno-type: congenital heart disease, milestones delay, velopharyngeal incompetence, hypocalcaemia, and mental retardation/psychiatric disturbances. CLINICAL FEATURES: congenital heart disease (84 %), velopharyngeal incompetence (47 %), milestones delay and learning disabilities (79 %). All of the deletions were de novo, except in one case where the deletion was present as mosaicism in the father. Three patients died, due to congenital heart disease. CONCLUSIONS: Clinical expression is widely variable, although a characteristic phenotype exists. Patients with heart disease are diagnosed earlier than other patients with unusual presenting phenotype such as congenital dysphagia. It is important to recognize less common phenotypes at early ages in order to provide multidisciplinary monitoring and accurate genetic counselling.

[Nephrolithiasis and topiramate]. / Nefrolitiasis y topiramato.

INTRODUCTION: Topiramate (TPM) is a new antiepileptic drug whose multiple mechanisms of action justify both its broad therapeutic spectrum and its increasingly widespread use in childhood epilepsy. TPM acts as a carbonic anhydrase inhibitor and, although this does not affect its effectiveness as an antiepileptic, it does account for certain side effects such as nephrolithiasis. The frequency of nephrolithiasis secondary to TPM in childhood is unknown and we have only found reports of five cases in children. CASE REPORTS: We describe two cases of medication-resistant infantile epilepsy--a 3-year-old female with Dravet's syndrome and a male aged 4.5 years with Lennox-Gastaut syndrome. In both cases the decision was made to introduce TPM as add-on therapy after a prolonged therapeutic programme; a high degree of effectiveness was achieved in both patients. Nevertheless, the two patients developed nephrolithiasis secondary to TPM, which in the second case was related to the simultaneous treatment with adrenocorticotropic hormone (ACTH), while no known favouring factor was found in the first patient. CONCLUSIONS: We outline the physiopathogenic mechanism explaining nephrolithiasis secondary to TPM, the risk factors involved and the therapeutic and preventive options available in dealing with this side effect, which occurs in a low percentage of cases but which usually means stopping administration of this therapy. We therefore believe it necessary to analyse the risk factors for nephrolithiasis before prescribing the drug and we suggest that generalised preventive measures should be implemented, especially in children who are carriers of encephalopathies or conditions that reduce mobility.

[Effectiveness and safety of levetiracetam in 133 children with medication resistant epileptic seizures]. / Eficacia y tolerabilidad del levetiracetam en 133 niños con crisis epilépticas farmacorresistentes.

INTRODUCTION: Levetiracetam (LEV) is the latest drug approved in the European Union for use in polytherapy in children over 4 years of age with partial epileptic seizures that are resistant to other antiepileptic drugs. AIM. To report our experience of associating LEV in children with medication resistant epileptic seizures. PATIENTS AND METHODS: We conducted an open, observational, respective study involving 133 children with refractory epilepsies: 106 with focal seizures and 27 with other types of seizures. LEV was associated over a period of more than 6 months and we evaluated its repercussion on the frequency of the seizures and the side effects related to the drug. RESULTS: With average doses of LEV of 1,192 +/- 749 mg/day the frequency of the seizures was reduced by over 50% in 58.6% of cases and seizures were quelled in 15.8% of patients. Side effects were produced in 27.8% of cases, and were usually transient or tolerable; these effects led to withdrawal of LEV in only eight cases (6.02%). In 37 children (27.8%), their relatives noted an improvement in their social behaviour and cognitive abilities. CONCLUSIONS: a) LEV is an effective drug that is well tolerated in children with refractory epilepsy; b) Its effectiveness in different types of seizures indicates a broad therapeutic spectrum; and c) LEV can even condition favourable secondary effects, a circumstance that has been reported only exceptionally in the case of other antiepileptic drugs.

[Characteristics and indications of tiagabine]. / Características e indicaciones de la tiagabina.

INTRODUCTION: Tiagabine (TGB) is an anti epileptic drug whose mechanism of action is due to a reduction in the neurone and astrocyte uptake of gamma aminobutyric acid (GABA), causing its concentration at the synapse to be increased. DEVELOPMENT: We analyze the most usual pharmacokinetic and pharmacodynamic characteristics of TGB, considering current therapeutic indications showing its increased use in seizures and partial epileptic syndromes. We also assess the adverse effects described, with special reference to the results obtained by the Spanish group investigating TGB, in a large number of patients with a wide range of ages. Finally we review the occurrence of status epilepticus induced by using TGB. CONCLUSIONS: It is defined as a gabaergic drug which is well tolerated and causes no visual field reduction. It may be used in epilepsies and epileptic syndromes which can be treated with it.

[Carpal tunnel syndrome in childhood. A case of early onset]. / Síndrome del túnel carpiano en la infancia. A propósito de un caso de debut precoz.

INTRODUCTION: The carpal tunnel syndrome (CTS) is the commonest neuropathy due to compression to be seen in adults. There are very few cases in the literature referring to patients of paediatric age, particularly those under ten years old. Most of these young patients had a metabolic disorder (mucopolysaccharidosis (MPS) or mucolipidosis (ML). In fact, as many as 90% of the MPS had CTS, sometimes subclinically. This syndrome is caused by compression of the median nerve at the level of the carpal tunnel, to which multiple factors may contribute, both local and systemic, as reviewed in this paper. The clinical findings differ from those in adults, but the appearance of suggestive symptoms and signs should make one suspect the condition and request an electromyographic study (EMG) which would be diagnostic. CLINICAL CASE: We describe the case of a five year old girl, with a clinical history suggesting the presence of a carpal tunnel syndrome for 12 months and characterized by paraesthesia and limitation of flexon-extension movements of the fingers of the affected hand, with pain on movement. The symptoms appeared on waking in the morning, gradually improved as the day advanced and became bilateral over a period of six months. The diagnosis was confirmed by EMG and MR helped to clarify the aetiology. CONCLUSION: The interesting aspect of this article is the youth of the patient, the absence of known etiological factors and the presence of tenosynovitis detected on MR as has been described in some idiopathic/familial forms.

[Infantile neuroaxonal dystrophy. A report of two new cases and a review of the literature published over the past ten years]. / Distrofia neuroaxonal infantil. Presentación de dos nuevos casos y revisión de los últimos diez años de la literatura.

INTRODUCTION: The neuroaxonal dystrophies make up a group of neurodegenerative disorders of unknown origin, which are characterized by all showing axonal lesions. The infantile form, or Seitelberger s disease, is one of the forms of earliest onset and rapid progression. The clinical, neurophysiological and pathological criteria described by Aicardi and Castelein in 1979 are still valid. However, we should emphasise the great usefulness of cerebral MR scanning in making an early diagnosis of this condition. CLINICAL CASES: We report two brothers, sons of consanguineous parents, who fulfilled the above clinical criteria. Their illness presented before the age of three years, with arrested psychomotor development followed by regression, an initial hypotonia syndrome which progressed to spastic tetraplegia, optic atrophy and progressive deafness, blindness and dementia. Neurophysiological findings were of central conduction disorders, and chronic denervation was shown on EMG. On EEG there were high frequency, high voltage rhythms. MR scanning showed the cerebral cortex to become atrophied and hyperintense at an early stage. On biopsy of the sural nerve and of skin there was spheroid swelling of the axons with tubulous vesicular material seen in myelinated and nonmyelinated axons. CONCLUSIONS: We reviewed the literature published over the past ten years (1990 2000). From this we conclude that on the initial clinical and neurophysiological criteria of Aicardi and with the aid of current neuroimaging techniques, the diagnosis may be suspected sufficiently early so as to permit genetic counselling. This would help to avoid further, high risk pregnancies, even before the diagnosis had been confirmed by the biopsy findings.

[Transient cognitive disorder from sub clinical paroxysmal EEG activity]. / Afectación cognitiva transitoria por actividad electroencefalográca paroxística subclínica.

INTRODUCTION: Transient cognitive disorder (TCD) defines the existence of a decrease in reaction time that coincides with an epileptiform EEG discharge, without any simultaneous manifestation of a classical epileptic seizure. Aims. To analyse the relation between episodes of TCD and the neurolopsychological manifestations in infancy that condition a high percentage of neuropaediatric visits to the surgery. At the same time we analyse the relation between the interictal paroxysmal disorders of patients with childhood benign partial idiopathic epilepsy with centrotemporal spikes (BIE CS) and the neurolopsychological manifestations that are frequently detected in such patients. PATIENTS AND METHODS: Two groups of patients were studied. Group A: 23 children who sought medical attention because of different neurolopsychological disorders (language retardation, hyperactivity, lack of attention, retarded academic achievement, behavioural disorders, bad social interaction); gender: 16 males and 7 females; age interval: from 2 years and 10 months to 11 years and 1 month (average age: 6 years and 8 months). Group B: 10 patients who were BIE CS carriers, two of which evolved toward atypical BIE; gender: 5 males and 5 females; age interval: from 3 years and 3 months to 9 years and 9 months (average age: 7 years and 4 months). Both groups were submitted to a clinical examination protocol involving neurological, EEG, child psychiatric and psychological aspects. RESULTS: In group A, sub clinical paroxysmal EEG discharges were seen in three cases, two of which corresponded to a lack of attention disorder with hyperactivity, and the third had a generalised growth disorder. In group B we detected a high percentage of perceptive and psychomotor disorders, without the existence of differences between those who displayed an irritative focus in the right or in the left hemisphere, although the alteration in the level of language was greater in the latter. Likewise, in a large percentage of cases (80%) the evaluation of the level of personality revealed obvious anxiety traits, which were related with suffering from seizures. CONCLUSIONS: Sufficient evidence has been found to demonstrate the existence of the possible relation between different neuropsychological disorders and epileptic EEG discharges, although revealing it in daily clinical practice requires a thorough diagnostic protocol and an accurate neuropsychological examination under video EEG monitoring, the positive results of which are considered to be decisive in evaluating the possibility of pharmacological treatment.

[Mitochondrial DNA depletion syndrome-13: a case with an unusual onset]. / Síndrome de depleción de ADN mitocondrial tipo 13: un caso con un inicio poco común.

TITLE: Síndrome de depleción de ADN mitocondrial tipo 13: un caso con un inicio poco común.

[Complex febrile crises: should we change the way we act?]. / Crisis febriles complejas: debemos cambiar nuestro modo de actuacion?

INTRODUCTION: Febrile seizures are one of the most frequent reasons why patients visit the healthcare specialist. Up until now, patients with complex febrile seizures (CFS) have been hospitalised, bearing in mind the higher percentages of epilepsy and acute complications that were classically reported. Today there are studies that back the idea of being less invasive in the management of these patients. AIMS. To describe the characteristics of patients hospitalised due to CFS and to propose a new protocol to be followed in dealing with such cases. PATIENTS AND METHODS: The medical records of patients hospitalised because of CFS (January 2010-December 2013) were analysed retrospectively. Epidemiological and clinical data are presented, together with information from complementary tests and about development. RESULTS: CFS account for 4.2% of all neuropaediatric cases of admittance to hospital in (67 patients). Mean age at the time of the event: 25 months. A pathological family history existed in 47% of cases, and 31% had a previous personal history of febrile seizures. The CFS lasted less than five minutes in 54% of patients; there were also recurrences, most of them with a total of two crises and during the first day (CFS due to recurrence are the most frequent). None of the complementary tests that were carried out were of any use as a diagnostic aid during the acute phase. During their follow-up, five patients presented complications. Patients with a family history of febrile seizures presented a higher risk of epilepsy or recurrence (p = 0.02), with no significant differences as regards age, number of seizures, febrile interval, epileptic status or type of CFS. CONCLUSIONS: The CFS are not associated with greater acute complications, and the complementary examinations do not allow high-risk patients to be distinguished at an early stage. Hospitalising them could be avoided in the absence of other clinical signs and symptoms, and thus be limited to selected cases.

TITLE: Crisis febriles complejas: debemos cambiar nuestro modo de actuacion?Introduccion. Las convulsiones febriles son una de las causas mas frecuentes de consulta. Hasta ahora, los pacientes con convulsiones febriles complejas (CFC) deben ingresar, dado el mayor porcentaje de epilepsia y complicaciones agudas descrito clasicamente. En la actualidad hay estudios que apoyan ser menos invasivos en el abordaje de estos pacientes. Objetivo. Describir las caracteristicas de los pacientes ingresados por CFC y proponer un nuevo protocolo de actuacion. Pacientes y metodos. Analisis retrospectivo de historias clinicas de ingresados por CFC (enero de 2010-diciembre de 2013). Se ofrecen datos epidemiologicos, clinicos, pruebas complementarias y evolucion. Resultados. Las CFC suponian un 4,2% de los ingresos de neuropediatria (n = 67). Edad media al evento: 25 meses. El 47% tenia antecedentes familiares patologicos, y el 31%, antecedentes personales de convulsion febril previa. En el 54% de los pacientes, la CFC duro menos de cinco minutos; hubo recurrencia, la mayoria con un total de dos crisis y durante el primer dia (las CFC por recurrencia son las mas frecuentes). De las pruebas complementarias realizadas, ninguna de ellas sirvio como apoyo diagnostico en el momento agudo. Durante su seguimiento, cinco pacientes presentaron complicaciones. Los pacientes con antecedentes familiares de convulsiones febriles presentan mayor riesgo de epilepsia o recurrencia (p = 0,02), sin diferencias significativas respecto a la edad, numero de crisis, intervalo de fiebre, estado epileptico o tipo de CFC. Conclusiones. Las CFC no asocian mayores complicaciones agudas; las exploraciones complementarias no permiten discriminar precozmente a los pacientes de riesgo. Su ingreso podria evitarse en ausencia de otros signos clinicos y limitarse a casos seleccionados.

[A descriptive study of neurocysticercosis in a tertiary care hospital]. / Estudio descriptivo de neurocisticercosis en un hospital terciario.

INTRODUCTION: Neurocysticercosis is the most frequent parasitic disease affecting the central nervous system. It is a disease that is endemic to certain countries in South America. The phenomenon of immigration, however, has increased its prevalence in developed regions due to the arrival of immigrants from endemic areas. AIM: To present the clinical and demographic characteristics of the cases of neurocysticercosis attended in a tertiary care hospital in the city of Murcia. PATIENTS AND METHODS: We conducted a descriptive, retrospective study by reviewing the medical records of patients with a hospital diagnosis of neurocysticercosis over a nine-year period (1997-2005). Demographic and clinical data on these patients were collected. RESULTS: Twenty-three patients (three under 12 years of age) were found. Mean age: 29.6 years. Countries of origin: Ecuador and Bolivia. The most frequently observed clinical manifestations were: epileptic seizures (73.9%), headache (39.1%) and neurological focus (26.1%). Albendazole was employed in 91.3% of cases and corticoids in 73.9%. The most frequently used drug in patients who received antiepileptic therapy was phenytoin. Four patients required surgical treatment. During the follow-up period, 52.8% of the patients were asymptomatic. CONCLUSIONS: Neurocysticercosis is a disease that is becoming increasingly more prevalent in Spain and we should suspect its presence in patients from endemic areas who visit because of clinical symptoms involving the central nervous system.

[Protocol guiding the procedure to be followed when faced with a suspected metabolic encephalopathy in infancy]. / Protocolo de actuación ante la sospecha de una encefalopatía metabólica en la infancia.

INTRODUCTION: Advances in the diagnosis and treatment of inborn errors of metabolism (IEM) have aroused renewed interest in these diseases in recent years. The vast degree of complexity involved in this pathology requires a great amount of effort in its diagnosis and, on many occasions, the need to resort to complex complementary examinations that can only be performed in specialised reference centres. AIMS. To review and outline the clinical features and diagnostic methods by drawing up a protocol to be followed in an attempt to offer care to these patients. Development and conclusions. We propose a diagnostic schema divided into three levels: the first level is based on the patient record, age at onset, and the signs and symptoms, which will enable us to establish the clinical suspicion of the type of IEM. On the second diagnostic level, the foregoing information is taken into account in order to decide whether it is advisable to carry out certain basal confirmatory tests in order to establish groups of biochemical patterns that allow us to get closer to an aetiological diagnosis. We believe that these basal tests should be available in most hospitals. A third level refers to employing specific diagnostic methods which are frequently carried out in reference centres. We also review metabolic encephalopathies that are associated to epilepsy and psychomotor or mental retardation due to their being the most common reasons for visits related to IEM in Neuropaediatric units.