Recent developments in the genetics of childhood epileptic encephalopathies: impact in clinical practice / Desenvolvimentos recentes na genética das encefalopatias epilépticas da infância: impacto na prática clínica

Recent advances in molecular genetics led to the discovery of several genes for childhood epileptic encephalopathies (CEEs). As the knowledge about the genes associated with this group of disorders develops, it becomes evident that CEEs present a number of specific genetic characteristics, which will influence the use of molecular testing for clinical purposes. Among these, there are the presence of marked genetic heterogeneity and the high frequency of de novo mutations. Therefore, the main objectives of this review paper are to present and discuss current knowledge regarding i) new genetic findings in CEEs, ii) phenotype-genotype correlations in different forms of CEEs; and, most importantly, iii) the impact of these new findings in clinical practice. Accompanying this text we have included a comprehensive table, containing the list of genes currently known to be involved in the etiology of CEEs.

Os avanços recentes em genética molecular permitiram a descoberta de vários genes para encefalopatias epilépticas da infância (EEIs). À medida que o conhecimento sobre os genes associados a este grupo de doenças se desenvolve, torna-se evidente que as EEIs apresentam uma série de características genéticas específicas, o que influencia o uso do teste molecular para fins clínicos. Entre as EEIs, há a presença de acentuada heterogeneidade genética e alta frequência de mutações de novo. Assim, os principais objetivos deste trabalho de revisão são apresentar e discutir o conhecimento atual a respeito de i) novas descobertas em genética molecular das EEIs, ii) correlações fenótipo-genótipo nas diferentes formas de EEIs; e, mais importante, iii) o impacto desses novos achados genéticos na prática clínica. Acompanhando o texto, incluímos uma tabela contendo a lista de genes conhecidos atualmente como envolvidos na etiologia da EEIs.

Clinical features and efficacy of different treatments on 5 cases with Landau-Kleffner syndrome with poor prognosis / 中华实用儿科临床杂志

Objective To analyze the clinical features and efficacy of different treatments on 5 cases with Landau-Kleffner syndrome (LKS) with poor prognosis.Methods Five patients with LKS who had poor prognosis were enrolled in the Children's Hospital of Fudan University from September of 2008 to December of 2012.The clinical features and findings of video electroencephalograph (VEEG) of these patients were analyzed.In addition,the outcomes of treatments (antiepileptic drug,corticosteroids and ketogenic diet) on LKS who had poor prognosis were studied.The outcome of epilepsy was classified by using the Engel classification scheme and the outcome of electrical status epilepticus during sleep (ESES) was classified by the decrease in spike wave index (SWI).Results All of 5 patients (2 male and 3 female) had auditory agnosia and epileptic seizure.All patients had normal background activity and epileptiform discharges,and the location of epileptiform discharge was mainly from bilateral temporal;3 patients had ESES.Four out of the 5 patients had refractory epilepsy and the other one got seizure free with antiepileptic drug.Four patients received corticosteroids for 6 months.The aphasia disappeared in 1 patient,improved in 1 patient and sustained in the other 2 patients.Three patients who had ESES did not response to corticosteroids.Among 3 patients receiving ketogenic diet,1 patient was seizure free and the ESES disappeared;in another SWI was reduced;the rest one had a significant reduction in seizure.All the patients had improvement in their aphasia and cognition,however they still had cognitive disorder of various degrees.Conclusions The patients who had multiple seizure type or special seizure type may have poor outcome.Most of these patients have refractory epilepsy or persistent ESES.Corticosteroids can improve aphasia and cognition,but the persistence of ESES can make aphasia and cognition worse.Ketogenic diet can be used as an alternative treatment for refractory epilepsy or persistent ESES in LKS.

Uso de flunarizina en un caso con síndrome de Landau-Kleffner / Use of flunarizine in a case of Landau-Kleffner syndrome

Introducción. El síndrome de Landau-Kleffner se caracteriza por afasia adquirida y anormalidades electroencefalográficas durante la vigilia y el sueño. El tratamiento con anticonvulsivos controla las crisis convulsivas pero en los problemas de lenguaje y comportamiento su eficacia es menor. Algunos reportes señalan mejoría de lenguaje con el uso de corticoesteroides en etapas tempranas y a dosis altas. Otra opción terapéutica es el uso de calcioantagonistas. Caso clínico. Paciente de 5 años de edad con evolución normal hasta los 2 años hasta que los padres observaron la pérdida espontánea del lenguaje previamente adquirido. En la evaluación neurológica se encontraron abundantes ecolalias e indiferencia a estímulos externos. El electroencefalograma mostró brotes intermitentes de ondas agudas y complejos punta-onda lenta de 3-4 Hz generalizados durante el sueño. Se inició tratamiento con prednisona por un mes y ácido valproico. Se continuó con el ácido valproico y después de 4 meses se añadió flunarizina, con lo que se observó mejoría en el lenguaje. Conclusiones. Este caso presenta los hallazgos clínicos y electroencefalográficos del síndrome; se observó que la mejor respuesta al tratamiento se obtuvo al agregar flunarizina. Esta evidencia contribuye a apoyar su uso y fundamenta la realización posterior de estudios controlados para concluir certeramente sobre su utilidad en el padecimiento.

Background. Landau-Kleffner syndrome is characterized by acquired aphasia and electroencephalographic abnormalities during wake-fulness and sleep. These abnormalities can be solved with anticonvulsive medications, but speech and behavioral problems cannot be treated using this therapy. Instead, there are reports that indicate that treatment with high-dose corticosteroids during early stages of the disease improves the speech difficulties. Use of calcium antagonists has also been proposed as possible treatment. Case report. We report the case of a 5-year-old patient with normal development until the age of 2 years. At that time, the parents observed loss of spontaneous acquired speech. During neurological evaluation, the child showed abundant echolalia and indifference to external stimuli. Electroencephalogram showed sharp waves and generalized slow spike-wave complexes of 3-4 Hz during sleep. We began treatment with prednisone and valproic acid for 1 month; flunarizine was added. After 4 months of treatment, the patient showed speech improvement. Conclusions. Our case has the characteristic clinical and electroencephalographic findings of Landau-Kleffner syndrome. We observed significant symptom improvement when flunarizine was added to the treatment. This evidence offers support for the use of a calcium antagonist as possible therapy, which may help setting the way for future controlled studies in order to finally establish its utility with this illness.

An Adolescent Boy with Acquired Epileptic Aphasia –Landau Kleffner Syndrome: A rare case report.

A 13 year adolescent boy presented with complaints of progressive loss of speech and seizure disorder for the past 1 year. The boy was developmently normal before the onset of illness. There was history of subtle trauma to head. He started communicating with signs followed by paucity of speech progressed to complete aphasia and abnormal behavior in the form of burst of aggressiveness and hyperactivity. Boy had partial, generalized tonic-clonic seizures occurred during sleep. Mental status examination revealed abnormal behaviour, attention deficits, auditory agnosia and aphasia (both expressive and receptive). All relevant investigations including BERA were normal.EEG showed repetitive spikes and wave activity in bilateral parietooccipital regions during nonrapid eye movement. Clinical features and EEG led to a diagnosis of Landau Kleffner Syndrome . He was started on Lamotrigine, steroid and speech therapy. The boy started showing improvement of symptoms in form of understanding of short sentences.

Advance in acquired epileptic aphasia / 国际儿科学杂志

Acquired epileptic aphasia is an age-related epilepsy syndrome. It is an epileptic encephalopathy. The etiology and pathogenesis is unclear. There are many progresses in pathogens, such as of susceptibility genes, the mechanism of autoimmunity, and the disorders of metabolism in brain and so on. But each theory can only explain a part of clinic symptom. In the progress of treatments, more recent case series show that sulthiame and levetiracetam can be considered as effective drugs. There are also progresses in corticosteroid,intravenous immunoglobulims and surgery treatment. Other new methods, such as diet and sign language, are applied in clinical therapy.

Landau-Kleffner syndrome without seizures: would speech delay justify the treatment with antiepileptic drugs?: [review] / Síndrome de Landau-Kleffner sem crises: atraso na aquisição da fala justifica o tratamento com drogas epilépticas?: [revisão]

INTRODUCTION: Landau-Kleffner Syndrome is a rare epileptic syndrome characterized by the association of receptive aphasia, epileptic seizures, behavioral disorders and electroencephalographic changes with discharges at the temporal lobe unilaterally or bilaterally. Seizures are not essential for diagnosis. CASE REPORT: J. V. S. S., 3 y/o male, with delay in acquirement of speech, psychomotor agitation and sleep disorder (sleeplessness). Attempt to communicate was established by gestures and pointing at things. His behavior characterized by agitation, restlessness, aggressiveness and difficulty to establish social contact with other children by the same age. MRI was normal and the EEG showed sharp-wave discharges in the left medial and posterior temporal regions. After three months of treatment with carbamazepine the child returned to an evaluation, presenting substantial improvement at speech, speaking simple words and with meaningful improvement on both behavioral and sleep patterns, as well as, social interaction. DISCUSSION: Expression and reception speech disorders are relatively common in children with different epileptic syndromes, particularly in Landau-Kleffner syndrome. Epileptiform discharges can occur in people without epilepsy and use to be called subclinical discharges. What would be the impact of subclinical discharges on this population remains uncertain at the present time. We reviewed these interactions in the light of a representative case, showing favorable outcome following introduction of an antiepileptic drug.

INTRODUÇÃO: Síndrome de Landau-Kleffner é uma síndrome epiléptica rara caracterizada pela associação de afasia de recepção, crises epilépticas, distúrbios do comportamento e alterações eletrencefalográficas com descargas nos lobos temporais unilaterais ou bilaterais. Crises convulsivas não são essenciais para o diagnóstico. RELATO DO CASO: J.V.S.S., masculino, três anos de idade, com atraso na aquisição da fala, agitação psicomotora e distúrbio do sono. Ele usava gestos e apontava para os objetos tentando se comunicar. Seu comportamento era muito agitado, impaciente, períodos de agressividade e muita dificuldade em estabelecer contato social com outras crianças da mesma idade. RNM foi normal e o EEG mostrou descargas de ondas agudas nas regiões temporais média e posterior esquerda. Após três meses de tratamento com carbamazepina a criança retornou para reavaliação, apresentando importante melhora da fala, falando palavras simples, melhora do comportamento e do padrão de sono e da interação social. DISCUSSÃO: Alterações na linguagem de recepção e de expressão são relativamente comuns em crianças com diferentes síndromes epilépticas, particularmente na síndrome de Landau-Kleffner. Descargas epileptiformes podem ocorrer em pessoas sem epilepsia sendo denominadas descargas subclínicas. Qual o impacto das descargas subclínicas para estas pessoas é incerto até o momento. Relatamos o caso de um menino com descargas epileptiformes no EEG, sem história de crises convulsivas e excelente evolução clínica após tratamento com droga antiepiléptica.

Two Cases of the Landau-Kleffner Syndrome / 대한이비인후과학회지

Landau-Kleffner syndrome, or acquired epileptiform aphasia, is an epilepsy syndrome with variable disruption of acquired language and epileptiform discharges on electroencephalograph (EEG). Auditory agnosia can deteriorate into total unresponsiveness and impaired expressive communication. In spite of the presence of this condition, the pure tone audiometry, otoacoustic emission and brainstem evoked auditory potential could be normal. Therefore, in the above hearing tests which are the mainstream methods for pediatric hearing evaluation, otolaryngologists should have suspicion for the presence of this syndrome, although it is rare.

Clinical Reviews of Landau-Kleffner Syndrome / 대한소아신경학회지

PURPOSE: We intended to describe the clinical features including characteristic etiologies, therapeutic approaches and outcomes for Landau-Kleffner syndrome(LKS). METHODS: A retrospective chart reviews were done to reveal the clinical and electrophysiological features in 5 patients who were diagnosed as LKS and undergone extensive diagnostic work-up and various therapeutic interventions. RESULTS: Among five LKS patients, 2 patients were males and 3 were females. All patients showed well controlled seizure outcomes but cognitive function including auditory and/or expressive aphasia were not improved in spite of using various anticonvulsants. Only two patients responded to steroid therapy but one patient showed repeated deterioration after discontinuation of the durg. Among 3 patients who were on ketogenic diet(KD), one patient showed a dramatic improvement in liguistic and cognitive functions in spite of underlying mitochondrial complex I deficiency. Multiple subpial transections (MST) were done in the other two patients because of incomplete recovery from ketogenic diet, and only one patient showed fairly successful improvement. CONCLUSION: Cognitive regression induced by LKS could be successfully improved by various therapeutic modalities including steroid, KD and palliative MST in most patients.

Clinical feature of Landau-Kleffner syndrome(report of 3 cases) / 临床神经病学杂志

Objective To investigate the clinical characteristics of Landau-Kleffner syndrome.Methods The clinical data of 3 patients with Landau-Kleffner syndrome was analyzed retrospectively.Results The clinical features of 3 cases presented acquired aphasia,epileptic attack and psychical behaviour abnormality.The EEG showed foci spike wave discharge,while the CT and MRI examination were normal.The epileptic attacks were controlled after treatment,but the recovery of aphasia and psychical behaviour abnormality was poor.Conclusions Acquired aphasia and epileptic attack are the clinical characteristics of Landau-Kleffner syndrome.The EEG shows spike wave dischargeis.Partial recovery can be obtained post-treatment.