Early prediction of encephalopathic transformation in children with benign epilepsy with centro-temporal spikes.

BACKGROUND: Most children with Benign epilepsy with centro-temporal spikes (BECTS) undergo remission during late adolescence and do not require treatment. In a small group of patients, the condition may evolve to encephalopathic syndromes including epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS), or Landau-Kleffner Syndrome (LKS). Development of prediction models for early identification of at-risk children is of utmost importance. AIM: To develop a predictive model of encephalopathic transformation using data-driven approaches, reveal complex interactions to identify potential risk factors. METHODS: Data were collected from a cohort of 91 patients diagnosed with BECTS treated between the years 2005-2017 at a pediatric neurology institute. Data on the initial presentation was collected based on a novel BECTS ontology and used to discover potential risk factors and to build a predictive model. Statistical and machine learning methods were compared. RESULTS: A subgroup of 18 children had encephalopathic transformation. The least absolute shrinkage and selection operator (LASSO) regression Model with Elastic Net was able to successfully detect children with ECSWS or LKS. Sensitivity and specificity were 0.83 and 0.44. The most notable risk factors were fronto-temporal and temporo-parietal localization of epileptic foci, semiology of seizure involving dysarthria or somatosensory auras. CONCLUSION: Novel prediction model for early identification of patients with BECTS at risk for ECSWS or LKS. This model can be used as a screening tool and assist physicians to consider special management for children predicted at high-risk. Clinical application of machine learning methods opens new frontiers of personalized patient care and treatment.

The Expanding Clinical Spectrum of Genetic Pediatric Epileptic Encephalopathies.

Pediatric epileptic encephalopathies represent a clinically challenging and often devastating group of disorders that affect children at different stages of infancy and childhood. With the advances in genetic testing and neuroimaging, the etiologies of these epileptic syndromes are now better defined. The various encephalopathies that are reviewed in this article include the following: early infantile epileptic encephalopathy or Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, West syndrome, severe myoclonic epilepsy in infancy (Dravet syndrome), Landau-Kleffner syndrome, Lennox-Gastaut syndrome, and epileptic encephalopathy with continuous spike-and-wave during sleep. Their clinical features, prognosis as well as underlying genetic etiologies are presented and updated.

Síndrome de Landau-Kleffner / Landau-Kleffner syndrome

El síndrome de Landau-Kleffner es un trastorno poco frecuente en niños, que debe sospecharse en pacientes que presentan regresión del lenguaje adquirido y muchas veces se asocian otras manifestaciones como crisis convulsivas, trastornos de conducta y alteraciones psiquiátrica. En este artículo se publica una revisión actualizada de esta patología, para que los pediatras consideren este diagnóstico en un niño con afasia.

Landau-Kleffner syndrome is not an eponymic badge of ignorance.

In a 1992 editorial article, Landau expressed the hope of collective agreement in the medical community about Landau-Kleffner syndrome (LKS) in terms of diagnosis criteria, etiology, pathophysiology and rational therapy. Since then, neurophysiological and neuroimaging studies have led to the view that LKS is an acquired aphasia, secondary to an epileptic disturbance affecting a cortical area involved in verbal processing. This fits with the hypothesis of a "functional ablation" caused by epileptic activity. Under these criteria, epileptic aphasia becomes a subgroup of the continuous spike-waves syndrome in which epileptic discharges originate from the temporal cortex. Genetic predisposition for KLS could be related to hyperexcitability and synchronization of interneurons within the perisylvian cortices, which generate the spike-waves. Activation of these waves during NREM sleep, following thalamo-cortical uncoupling, might then alter the blood brain barrier and provoke an autoimmune reaction. Interneuron hyperactivity might in turn have an antiepileptic protective effect, associated with the inhibition of a specific function, and spike-waves activity over the long term might eventuate in focal atrophy. This morphological defect might explain the poor verbal outcome in some cases of LKS. From this study we recommend a multicenter control study of good design and methodology be carried out to compare the efficacies of early versus delayed (3 months) corticosteroid treatment in patients with typical LKS that is being treated by clobazam (or diazepam) monotherapy.

Afasias adquiridas: síndrome de Landau-Kleffner y otros / No disponible

Objetivo. Presentar las características clínicas-EEG del síndrome de Landau-Kleffner (SLK) o afasia epilépticaadquirida, discutir sus aspectos etiopatogénicos y sus relaciones con la epilepsia rolándica y la epilepsia con punta onda continuadurante el sueño lento (EPOCSL), y establecer el diagnóstico diferencial con otras afasias adquiridas y trastornos delespectro autista (TEA). Desarrollo y conclusiones. El SLK es un síndrome epiléptico raro con fenotipo clínico-EEG bien establecido–agnosia auditiva con crisis epilépticas, en un alto porcentaje, de buen pronóstico, otros trastornos neuropsicológicos,y EEG con punta onda continua en sueño lento (POCSL)– y una etiopatogenia no bien delimitada. La mayoría de loscasos son criptogénicos y en pocos casos se han encontrado agentes causales diversos, destacando entre ellos microdisgenesiascorticales. La afasia de recepción está originada por las POCSL que ocurren en periodos críticos de la maduración cerebral,durante la sinaptogénesis cortical bitemporal, cuando se establecen los circuitos funcionales elementales lingüísticos.Es probable que haya un factor genético implicado que, activado por factores medioambientales, desencadene el síndrome. ElSLK se relaciona por la edad de comienzo, anomalías del EEG intercrítico y activación por el sueño con otros síndromes que,a veces, se solapan entre ellos, como la epilepsia rolándica y la EPOCSL, con los cuales constituyen un continuo neurobiológicocuya expresión clínica neuropsicológica se relaciona con el punto de partida de las descargas, y la gravedad, con la activaciónen sueño. En el diagnóstico diferencial con otras afasias adquiridas y TEA, aparte de matices clínicos, a veces claros,los hallazgos del EEG en sueño son definitivos. El tratamiento incluye fármacos antiepilépticos y/o corticoides, apoyo psicopedagógicoy, en ocasiones, cirugía

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Epilepsy, antiepileptic drugs (AEDs) and cognition.

People with epilepsy are at increased risk of cognitive deficits as a result of various factors: the effect of seizures themselves, psychosocial factors and adverse effects of AEDs. It is crucial that, following early diagnosis of the correct epileptic syndrome, patients are treated with the appropriate drugs, as incorrect AEDs can exacerbate symptoms. By discussing various epileptic syndromes and performing a broad review of the available evidence, it is possible to make recommendations concerning prescription of AEDs with respect to cognition. An interesting advance in this area is the increasing use of AEDs such as valproate (in some countries divalproex is indicated), carbamazepine or lamotrigine (lamotrigine has been filed for approval in this indication) for bipolar disorders. Children and the elderly are especially vulnerable to adverse effects on cognition. This review highlights advantages of valproate in these populations; it is well tolerated and produces few cognitive side effects.

Landau-Kleffner syndrome (acquired epileptic aphasia) in a Nigerian child.

Epilepsy is one of the commonest disorders presenting the neurological clinics in developing countries. There are attendant complications especially in untreated or poorly treated cases. In this article, we report an uncommon complication known as Landau-Kleffner syndrome in a Nigerian girl. The syndrome, typically seen in children consists of an acquired aphasia frequently associated with clinical seizures and paroxysmal electroencephalographic (EEG) accompaniment. There had been no adequate neuropathlogical correlations to explain the symptomatology; thus, various forms of pathogenesis have been ascribed to the syndrome. The clinical seizure is easily controlled by an antiepileptic; but speech recovery is variable, and this is usually poor in cases presenting one or two years after onset.

Landau Kleffner syndrome: electroclinical and etiopathogenic heterogeneity.

Landau - Kleffner syndrome is a rare, functional, age-related epilepsy with aphasia and epileptiform discharges on EEG. The heterogenity of clinical presentations, course, long-term outcome and response to treatment suggests multiple underlying etiologies. Normal children abruptly develop deterioration of language functions along with spike and wave discharges on EEG. Clinical seizures may or may not be present. The aphasia responds poorly to most drugs. Valproic acid and benzodiazepines are most effective. Steroids and intravenous immunoglobulins have shown a variable response. Long-term outcome of aphasia is variable, many patients persist with residual impairment. Important questions regarding etiopathogenesis are unanswered.

A chance SPECT study of ictal aphasia during simple partial seizures.

We report obtaining an ictal single photon emission computed tomographic (SPECT) scan in a right-handed 51-year-old man who had an astrocytoma in the left cerebral hemisphere and simple partial seizures characterized by aphasia. An epileptic seizure producing loss of speech and right-sided facial twitching occurred by chance during a SPECT scan. During the attack, he was unable to speak, but auditory comprehension and writing were intact. Ictal SPECT showed an area of increased perfusion in the left frontal cortex, with the area of highest perfusion involving the left frontal operculum to the inferior part of the left precentral gyrus. Interictal SPECT showed hypoperfusion in the same area. These SPECT findings suggest that the frontal operculum of the dominant hemisphere is one of the regions that can give rise to epileptic aphasia.

[Early, middle-latency and late auditory evoked potentials in a case of acquired epileptic aphasia (Landau-Kleffner syndrome)]. / Les potentiels évoqués auditifs précoces, de latence moyenne et tardifs dans un cas d'aphasie acquise-épilepsie (syndrome de Landau-Kleffner).

The authors report the case of a girl whose development was normal until the age of eleven when epileptic seizures occurred. These were followed by loss of speech and auditory agnosia. The diagnosis of Landau-Kleffner syndrome was mode. The study of the auditory evoked response showed normal function of ear and brainstem auditory relays. On the other hand, the amplitude of the middle latency and late cortical responses were decreased. The relationship between these electrophysiological abnormalities and auditory agnosia are discussed.

[Landau-Kleffner syndrome (acquired aphasia with epilepsy). Etiopathology and response to treatment with anticonvulsants]. / Síndrome de Landau-Kleffner (afasia adquirida con epilepsia). Etiopatogenia y respuesta al tratamiento anticonvulsivo.

The Landau-Kleffner syndrome consists in the association of an aphasia acquired during childhood or adolescence after a period of normal development, accompanied by epileptic fits and, sometimes, psychological disturbances. The appearance of the symptoms may not be simultaneous. The nature of this syndrome has been widely discussed and even the possibility of being a non-unitary syndrome has been considered. It may be possibly due to diverse etiologies, genetic or acquired (infectious). The relation between the aphasic, the psychologic and the convulsive symptoms has also raised controversies. A case of a female is described in which the psychological symptomatology was so severe, she had to be admitted in a psychiatric unit. The symptoms consisted in agitation during the night and severe persistent insomnia so as difficulties for relationship during day. No abnormalities were detected in a TAC nor in a RM but electroencephalographic and neuropsychological abnormalities were detected. The epileptic fits disappeared with a carbamacepine treatment but the rest of symptoms remained even more accentuated. After her admission, a treatment with valproate achieved to control her fits and the aphasic symptoms and neuropsychological deficits were compensated in the course of several months. After a year of treatment the patient's life was normalized, she resumed her studies, the EEG abnormalities disappeared so as the psychological disturbances and the behavior problems with the exception of phobic symptoms, similar to the ones of other family members. The patient has a history of epilepsy on its mother's side. The evolution and treatment response suggests that at least in some cases of the Landau-Kleffner syndrome, the etiology of the aphasia and other neuropsychological deficits and of the behavior disorders are related with some subclinical epileptic discharges and with a "functional inhibition" of some areas of the nervous system.

Aphasic status epilepticus in multiple sclerosis.

Aphasia due to simple partial status epilepticus is rare. We report a case of prolonged mixed aphasia without clouding of consciousness in a patient with an old history (10 years) of multiple sclerosis (MS). We found a clear clinical-EEG correlation with a continuous epileptic pattern in the shape of periodic lateralized epileptiform discharges (PLEDs). Clinical, laboratory and neuroradiological data ruled out possible etiological conditions other than MS and suggested that the development of new subcortical demyelinating lesions might play a critical role in seizure production. These findings, besides the role of PLEDs as an intrinsic feature of the status epilepticus condition, are discussed in relation to the literature.

The Landau-Kleffner Syndrome: a review.

The Landau-Kleffner syndrome or the syndrome of acquired epileptic aphasia was first described in 1957. The disorder is characterised by gradual or rapid loss of language in a previously normal child. All children have abnormal EEG compatible with the diagnosis of epilepsy, however, only 70% have clinical seizures. The present article presents a review of the current knowledge concerning this disorder. Information is provided related to the clinical picture, etiology, pathogenesis, treatment and outcome.