Usefulness of Video-EEG monitoring in patients with drug-resistant epilepsy.

OBJECTIVE: To evaluate the characteristics of patients on whom long-term Video-EEG monitoring is performed in a specialist centre and to assess its suitability to study refractory epilepsy patients. METHODS: A prospective analysis and study of Video-EEG monitoring was performed in a series of 100 refractory epilepsy patients from a single centre. The analysis included demographic data, the time until the first seizure, the methods used to provoke seizures, and the outcome (usefulness, change in the management, pharmacological and surgical improvement). A subgroup analysis based on diagnosis was performed. RESULTS: The study was performed mainly on young people (mean 34.4 years) and the first seizure appeared in a mean of 30hours, requiring most of the patients to withdraw the medication. Nevertheless, there were no cases of status epilepticus. The usefulness of the test was high in all the groups. The management was changed in 65% of the patients with pharmacological and surgical improvement. CONCLUSION: Long-term Video-EEG monitoring is a suitable test to study refractory epilepsy patients. The main problem in our country is accesibility.

Mapping of Friedreich's ataxia locus by identification of recombination events in patients homozygous by descent.

The Friedreich's ataxia locus (FRDA) maps on chromosome 9q13. Genetic data, obtained from a small number of recombination events, indicated that the FRDA locus might be located centromeric to the D9S15/D9S5 linkage group, the most probable order being cen-FRDA-D9S5-D9S111-D9S15-D9S110-qter. Recently, new centromeric markers have been reported. Analysis of these markers allowed us to localize the recombination breakpoint in some of the recombinant families. However, only one proximal recombination has been found with these markers. To increase the genetic information from FRDA families, we have analyzed the centromeric markers FR1, FR2, FR7, FR8, and FR5 in patients homozygous by descent. These were ascertained because parents were consanguineous or because they were homozygous for the entire haplotype D9S15 or D9S111-D9S5-D9S411E-D9S202. Haplotype divergence for, at least, two contiguous markers was observed in two patients homozygous for the core D9S111-FR2 haplotype and in one third-degree consanguineous family homozygous for haplotype D9S411E-FR5. Interpretation of divergence as the result of ancient meiotic crossovers allowed the definition of three new recombination events which place the FRDA locus within the interval defined by markers D9S411E and FR8. A consanguineous family with first-cousin parents showed homozygosity only at D9S202 and FR2. Further investigations are needed to discern whether two different mutations are segregating in the family or whether two recombinations, one distal and one proximal, have taken place.

[Headaches in childhood: association with sleep disorders and psychological implications]. / Cefaleas en la infancia: asociación a trastornos del sueño e implicaciones psicológicas.

INTRODUCTION: Infantile headache is an increasingly important cause of medical consultation, due both to its increasing prevalence and its subsequent repercussion on the child's life. Also, certain sleep disorders (parasomnias) are commoner in infancy than in later life. The relationship between headache and sleep disorders is not clear, but from the literature it would seem that there is an association, at least in some types of headache, in adults. PATIENTS AND METHODS: In order to determine possible alterations in patterns of sleep in children with chronic headache (a history of headache during the previous six months occurring more than 15/month or 180 days/year) we carried out a comparative study on a total of 224 Valencian children aged between 3 and 15 years. Of these, 97 children had been diagnosed as having primary chronic headache (cases) in a specialized. PAEDIATRIC NEUROLOGY CLINIC: Twenty seven healthy children with no history of headache (controls) were found amongst the pupils of a Valencian state school. Using a purpose-designed sleep questionnaire, data was obtained as to the duration, hygiene, quality and incidence of parasomnia in the two groups. RESULTS: The results showed a decrease in duration of sleep at night, increased frequency of poor sleep hygiene, increased prevalence of certain sleep disorders (insomnia and nocturnal wakening), of certain parasomnias (somnambulism, somniloquy, enuresis) and of nocturnal snoring, all of statistical significance (test chi 2 with p < 0.005). CONCLUSION: In children there is an association between chronic headache and certain sleep disorders.

[Studies of evoked potentials in children with the syndrome of attention deficit and hyperactivity]. / Estudios de potenciales evocados en niños con síndrome por déficit de atención e hiperactividad.

INTRODUCTION: The syndrome of attention deficit and hyperactivity (SADH) is a frequent diagnosis in school children, based on clinical criteria systematized in the DSM-IV and the ICD-10. Nevertheless, there is no biological marker sufficiently sensitive and specific to confirm the diagnosis and clarify the physiopathological mechanism of this disorder of psychological development. DEVELOPMENT: For this, endogenous evoked potentials especially the P300 wave, related to the processes of selective attention and sensory elaboration of discriminatory stimuli, have been used. In order to study the type of alteration in the P300 wave of children diagnosed as having SADH, and the changes induced after two months of treatment with methylphenidate (MF), 12 children were studied. The paradigm of oddball type auditory stimulation was used. The latency and wavelength of the P300 wave at the Cz electrode before (basal) and 2 hours after taking 10 mg of MF were determined. Comparative analysis of the average latencies before and after administration of MF showed significant differences (p < 0.01), with a shortening of the latency following treatment. No significant changes were seen in amplitude. In only two patients (17%) were there no differences in the latency of response before and after treatment, and no response at all to treatment. CONCLUSION: These results show the practical usefulness of study of the P300 wave in children with SADH, at least for monitoring the efficacy of pharmacological treatment.

[Muscular dystrophies due to alterations at extracellular space level: congenital muscular dystrophy caused by merosin deficiency]. / Distrofias musculares por alteración en el espacio extracelular: distrofia muscular congénita por déficit de merosina.

OBJECTIVE: This is an up-to-date analysis of congenital muscular dystrophies (CMD), especially merosin-deficient-CMD, we also present our center expertise. DEVELOPMENT: CMD are skeletal muscle degenerative hereditary diseases caused by abnormal synthesis of structural or functional muscle proteins. Severe hypotonia, joint deformities and muscle weakness at birth are the main features of CMD. A especial type of CMD caused by absence of alpha 2 chain (or merosin) of laminin 2, a tissue specific protein from muscle basement membrane which anchors extracellular matrix to dystrophin, is the paradigm of a muscular dystrophy produced by extracellular abnormalities. CMD merosin-negative locus was assigned to chromosome 6q2, where is localized the laminin alpha 2 chain gene (LAMA2). Recently, LAMA2 gene mutations producing the disease have been described. Floppy infant syndrome is its earliest symptom and CMD merosin-negative represents the most frequent cause of muscular origin. 40% of our CMD patients are completely merorin-deficient. They had marked delayed motor milestones and never became ambulant but their intelligence remainded normal. Nowadays we can perform a prenatal diagnosis by immunohistochemical analysis in trophoblast. CONCLUSION: CMD merosin-deficient represents a subset of patients with a potentially poor prognosis, thus an early diagnosis is highly convenient in order to establish a correct follow-up [REV NEUROL 1999; 28: 141-9].

[Treatment and prevention of cerebral hemorrhage in newborns]. / Tratamiento y prevención de las hemorragias cerebrales en el recién nacido.

INTRODUCTION: The risk factors leading to the occurrence of intracranial hemorrhages in premature newborn babies are well known. However, in full-term babies this has not been so systematically studied. Although the incidence is lower it is not rare and they are more varied in the form of presentation than in premature babies. Thus, as well as the classical intraperiventricular hemorrhages, subarachnoid and intraparenchymatous hemorrhages also occur relatively often, particularly the subarachnoid kind. The aetiopathogenesis of the hemorrhages is different, so preventive measures are also different, based particularly on avoidance of perinatal asphyxia and traumatic manoevres during labour. DEVELOPMENT: A study by our Department, in which risk factors associated with 17 newborn babies of over 35 weeks gestation who had a history of intracranial hemorrhage in the early neonatal period showed that over half the cases (58%) had a history of acute foetal distress. A quarter had congenital cardiopathy (detected at birth) and the same number had a respiratory distress syndrome due to various causes, particularly pneumothorax and infections. Regarding treatment of the acute phase, it is essential to maintain cerebral perfusion and monitor both arterial hypertension and hypotension, control the intracranial pressure (avoiding increases) and avoid fluctuations of cerebral blood flow. CONCLUSION: Follow-up by means of serial echographs makes early detection of dilatation and hydrocephaly possible and permits suitable suitable treatment rapidly and with immediate monitoring of its efficacy.

[Alternating hemiplegia in young babies]. / Hemiplejía alternante del lactante.

INTRODUCTION. This paper review the state of the art of alternating hemiplegia of childhood. This entity is a rare neurologic disorder of infancy characterize by transient hemiplegic spells shifting from one side to another, and occasionally affecting to both hemispheres at the same time. Usually start before 18 months, many cases exhibit neonatal symptoms related with the disorder. Early symptomatology include abnormal ocular movements, mainly nystagmus, and tonic or dystonic attacks generally beginning before 6 months of age. These symptoms are frequently misdiagnosis as epilepsy. Typical hemiplegic fits which disappeared when infant felt asleep appeared by 12 months of age. Diagnosis is on clinical basis after excluding any other causes of fluctuating and transitory hemiplegic attacks. Complementary investigations, such as electroencephalograms, TAC, MRI, angiographic MRI, CFS are strictly normal. Cerebral SPECT show controversial abnormalities in some studies. We perform SPECT study in a alert 12 months old girl during an interictal period resulting in a non significant asymmetry, with lesser perfusion in left frontal basal and anterior temporal gyrus. Nevertheless, we observed an striking hyperperfusion in middle occipital area. Treatment is symptomatic with flunarizine. Our patient experience a dramatic decrease in frequency, duration and severity of hemiplegic attacks.

[Periventricular leukomalacia: neurological and radiological sequelae and long term neuropsychological repercussions]. / Leucomalacia periventricular: secuelas neurológicas, radiológicas y repercusiones neuropsicológicas a largo plazo.

INTRODUCTION: Periventricular leukomalacia is an anatomical diagnosis made by neuroimaging technics, of hypoxic-ischemic origin and a characteristic neurological syndrome consisting in cerebral palsy, visual impairment and/or mental retardation. Is more frequently seen in pre-term infant (5-10%) as a spastic diplegia or tetraplegia. Real prevalence in a-term infant is unknown and is presented as hemiplegia. The correlation between periventricular leukomalacia severity and clinical severity is not absolutely clarified. Is not still known if we can predict mental retardation in an infant with periventricular leukomalacia on magnetic resonance image. DEVELOPMENT: This paper revise the clinical and radiological diagnosis of periventricular leukomalacia and shows the results of a series of 31 patients diagnosed radiologically of periventricular leukomalacia. We correlate the degree of neurological and mental disabilities with the severity of periventricular leukomalacia. CONCLUSION: We reach a good correlation between the severity of periventricular leukomalacia and the severity of neurological disturbances and mental retardation.

[Disseminated acute encephalomyelitis in children. A retrospective study of seven patients]. / Encefalomielitis aguda diseminada en la infancia. Estudio retrospectivo de siete pacientes.

INTRODUCTION AND OBJECTIVE: Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system. This study is based on clinical symptoms and diagnostic tests employed. PATIENTS AND METHODS: We describe a seven children series indicating the initial neurologic abnormalities, diagnostic tests, treatments used and clinical-neuroradiological evolution. RESULTS: The mean presentation age was 4.1 years. Initial neurologic symptoms were mainly spastic hemi/paraparesis, cerebellous and pyramidal syndrome, consciousness changes, meningeal signs, seizures and cranial nerve palsies. The cerebrospinal fluid was abnormal in four patients with positive serologic tests in two of them (Coxsackie B). Electrophysiological studies were affected in 50%. MRI findings consisted of multifocal supratentorial white matter lesions. Clinical evolution revealed a progressive improvement with resolution after two months. Follow-up was made between six months and five years. The treatment was based on aciclovir and corticosteroids. CONCLUSIONS: ADEM runs a monophasic course of progressive neurologic abnormalities. Diagnosis is based on suggestive clinical and neuroimaging findings. Generally speaking, MRI showed resolution of multifocal lesions in conjunction with clinical improvement.

[Familial periodic ataxia with myokymia sensitive to acetazolamide: a family case]. / Ataxia periódica familiar con mioquimia sensible a acetazolamida: presentación de una familia.

INTRODUCTION: Acetazolamide responsive hereditary paroxysmal cerebellar ataxia with myokymia is a type of autosomal dominant cerebellar ataxia which locus was found to be linked to the short arm of chromosome 12 and the etiology is unknown. CLINICAL CASE: A 12 years-old man who suffered from childhood daily episodes of sudden attacks sport induced with giddiness, ataxia and dysarthria for minutes. The familial history shows the same clinical findings in three generations. Intercritical general neurologic evaluation is otherwise normal. The following tests were performed with normal results: Biochemistry, electroencephalogram, cerebral magnetic resonance imaging. The electromyography showed myokymic discharges. The patient's symptoms improve on treatment with acetazolamide immediately. CONCLUSIONS: Acetazolamide responsive hereditary paroxysmal cerebellar ataxia with myokymia needs to think on it to be diagnosed. No typical complementary test (electromyography exception) induces to base diagnosis in the clinical findings, the familial history and the fast clinical improvement after starting treatment with acetazolamide.

[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.

[Hypothalamic hamartoma: clinical characteristics. Electroencephalogram and brain magnetic resonance imaging in 10 patients]. / Hamartomas hipotalámicos: características clínicas, electroencefalograma y resonancia magnética cerebral en 10 pacientes.

INTRODUCTION: We describe clinical findings and electroencephalogram (EEG) in patients with hypothalamic hamartoma and epilepsy. METHODS: Our group includes 10 patients (eight males) with mean age of 17.8 years (range: 7-39) and hypothalamic hamartoma in the brain magnetic resonance imaging (MRI). We analyzed clinical data, seizure semiology, MRI and EEG findings of the neuropsychological study. RESULTS: Nine patients had gelastic seizures, that initiated at a mean age of 17.1 months (2 days-5 years). Other types of seizure were observed in seven and five had behavior disorders. Intelligence quotient (IQ) was below the mean range in three. Three children had precocious puberty and thyroid dysfunction. One patient did not have epilepsy. MRI showed a hypothalamic lesion suggesting hamartoma associated to a dysplastic lesion in one case. The interictal EEG was normal in 2 cases and revealed epileptiform abnormalities, consisting of spikes or sharp waves, in temporal regions, frontal, fronto-temporal regions and central-parietal in 8. Three patients had paroxysmal discharges of generalized fast activity (> 10 Hz) during non-REM sleep. Forty seizures were recorded, 31 had an ictal EEG pattern while the EEG was normal in 9. CONCLUSIONS: In our group gelastic seizures were an early and constant finding except in one patient. Partial complex seizures, behavior alteration and cognitive decline were frequent. Video-EEG monitoring allows us to identify interictal and ictal patterns that have been described in hypothalamic hamartomas.

Prenatal diagnosis of Friedreich ataxia: improved accuracy by using new genetic flanking markers.

Friedreich ataxia is a neurodegerative disorder with autosomal recessive inheritance. Since the gene causing mutation has not yet been identified, prenatal, predictive, and carrier diagnoses are based on indirect haplotype analysis with closely linked markers. Until recently, only distal markers were available and their physical distance to the Friedreich ataxia (FRDA) gene remained elusive. The identification of close flanking markers that mark out the boundaries of the FRDA locus and reduce the critical genomic region which contains the gene allows for the first time misdiagnosis due to undetectable recombination to be avoided and diagnosis accuracy to be greatly improved. In this sense, we have verified a prenatal diagnosis in which the fetus was diagnosed as an unaffected carrier last year with a confidence of 95 per cent. By using the new flanking markers, the diagnosis improved and confidence reached almost 100 per cent.

A family segregating a Friedreich ataxia phenotype that is not linked to the FRDA locus.

Friedreich ataxia is an autosomal recessive neurodegenerative disorder. The genetic homogeneity to the FRDA locus on chromosome 9q13-21.1 has been observed in families from different ancestries. We report a Spanish family with two affected and three unaffected children. The segregated classical Friedreich ataxia did not show the expected linkage. The analysis focusses on flanking markers FR1, FR2, FR7 and FR5, excluding linkage 1 cM around the FRDA locus. The unique clinical hallmark in this family was the absence of cardiomyopathy after a long-term follow-up in the two affected children. In both patients serum vitamin E levels were normal. The present observations support the existence of a second locus in Friedreich ataxia, and we suggest that this form could be clinically characterized by the absence of muscular heart disease.

Early-onset ataxia with cardiomyopathy and retained tendon reflexes maps to the Friedreich's ataxia locus on chromosome 9q.

Absence of lower limb tendon reflexes has been considered an essential diagnostic criterion for Friedreich's ataxia (FA). However, preservation of knee and ankle jerks has been reported in a few patients. Linkage analysis to FA locus (FRDA) on chromosome 9q13-21.1 was performed in 11 patients from 6 families with FA phenotype, including cardiomyopathy, but retained reflexes (FARR). A maximal lod score of 3.38 at recombination fraction theta equal to 0.00 was obtained demonstrating that FARR maps to the FRDA locus. These results suggest that FARR is a variant phenotype of FA.

Unique origin and low penetrance of the 946delGAG mutation in Valencian DYT1 families.

Mutations in the DYT1 gene cause idiopathic torsion dystonia (ITD) transmitted in families as an autosomal dominant trait with incomplete penetrance. The most common mutation, 946delGAG, has been observed in populations with different ethnic and geographic origins. We have investigated 40 individuals from 22 unrelated families with ITD originating from the Land of Valencia, Spain, for the presence of this mutation and we found 5 patients and 6 unaffected subjects from 4 families who were carriers of the mutation. This finding indicates that 18% of families may be diagnosed as DYT1 and that penetrance is reduced. We detected two different geographic and linguistic origins of the Valencian families. However, by haplotype analysis using D9S1260, D9S1261, D9S63 and D9S1262 as flanking markers, we demonstrated that all affected and unaffected carriers shared a common chromosome confirming identical origin of the mutation in the four families. We postulate a unique origin for the 946delGAG mutation in the Land of Valencia and, based on linguistic criterion, we propose that the mutation might have occurred at the beginning of the second millennium. Genetic analysis of another family from Castilla-La Mancha showed a different haplotype segregating with the disease, suggesting that at least two distinct mutational events for the 946delGAG mutation have occurred in Spain.