Epidemiological study of Landau-Kleffner syndrome (LKS) in Japan.

OBJECTIVE: We aimed to determine the incidence and prevalence of LKS in Japanese children. METHODS: A questionnaire was sent to all 3004 Japanese hospitals that have a department of pediatrics. The questionnaire asked for the number of first-visit LKS patients and LKS patients who were followed up at or visited their clinic during the past one year Vital statistics of the same year (2008) published by Ministry of Health, Labor and Welfare, Japan were referenced to calculate the estimated incidence and prevalence of LKS among Japanese children. RESULTS: Chiefs of 1562 pediatric departments answered our inquiry (51.9% of returns). Six chiefs had one new LKS patient, aged 6-14 years. Thirty two patients with LKS were followed in the same period. The number of children with LKS less than 20 years of age who needed medical care was at least 23 and at most 31. Vital statistics of Japan 2009 revealed that the population of children aged 5-14 years was 11,861,464 and that aged 5-19 years was 18,007,968. DISCUSSION: The number of the first-visit LKS patients was 6 in a year. We estimated the incidence of LKS in the 5- to 14-years-old Japanese population as about 1 in 978,000. The number of LKS patients aged 5-19 was estimated to range from 44.2 to 59.6 among a population of 18,007,968. This means the prevalence of LKS under medical care is roughly one in 302,147-407,420 children aged 5-19. This study is the first epidemiological estimation of the incidence and prevalence of children with LKS in Japan or, for that matter, in any other area. CONCLUSION: (1) Incidence of children with LKS aged 5-14 years was about 1 in a million in Japan. (2) Prevalence of children with LKS aged 5-19 and under medical care was one in about 300,000-410,000 in Japan. (3) This study constitutes the first epidemiological estimation of LKS in Japan.

Landau-Kleffner syndrome in Norway: long-term prognosis and experiences with the health services and educational systems.

We have conducted a retrospective study based on the medical records of 19 children with Landau-Kleffner syndrome and semistructured interviews of their parents. There was considerable heterogeneity in the children's symptoms. Eleven children were followed for more than 10 years (mean=14.4 years); four have normal language, four have moderate language problems, and three have no functional verbal language today. Late-onset language decline, short duration of the initial aphasic period, and marked fluctuations in speech abilities appeared to be associated with a positive outcome with respect to future language skills. The parents reported having to argue strongly with the health authorities and educational system to obtain a correct diagnosis and receive adequate help. Their main concern was not being taken seriously when they expressed their worries, and they expressed a strong wish for someone who could ensure that appropriate support measures were implemented and who could coordinate assistance.

Encephalopathy with status epilepticus during slow sleep: "the Penelope syndrome".

ESES (encephalopathy with status epilepticus during sleep) is an epileptic encephalopathy with heterogeneous clinical manifestations (cognitive, motor, and behavioral disturbances in different associations, and various seizure types) related to a peculiar electroencephalography (EEG) pattern characterized by paroxysmal activity significantly activated during slow sleep-that is, a condition of continuous spikes and waves, or status epilepticus, during sleep. The pathophysiologic mechanisms underlying this condition are still incompletely understood; recent data suggest that the abnormal epileptic EEG activity occurring during sleep might cause the typical clinical symptoms by interfering with sleep-related physiologic functions, and possibly neuroplasticity processes mediating higher cortical functions such as learning and memory consolidation. As in the myth of Penelope, the wife of Odysseus, what is weaved during the day will be unraveled during the night.

Atypical rolandic epilepsy.

Typical benign rolandic epilepsy (BRE) is a frequent and well-delineated epileptic syndrome in childhood. Mild cognitive and behavioral difficulties are increasingly recognized in the course of BRE and should not be considered as atypical features. Atypical features are recognized on electroclinical grounds. These features, particularly early age at onset and frequent spikes or spike-wave discharges, seem to be risk factors for neuropsychological deficits but also for an atypical evolution of BRE. Atypical evolutions of BRE are defined by the appearance of severe neuropsychological impairments and continuous spike-and-waves during slow sleep (CSWSS). The clinical expressions of these situations correspond to the syndromes known as atypical benign focal epilepsy of childhood (ABFEC), status of BRE, Landau-Kleffner syndrome (LKS), and CSWSS syndrome, which may be part of a continuum related to BRE.

CSWS-related autistic regression versus autistic regression without CSWS.

Continuous spike-waves during slow-wave sleep (CSWS) and Landau-Kleffner syndrome (LKS) are two clinical epileptic syndromes that are associated with the electroencephalography (EEG) pattern of electrical status epilepticus during slow wave sleep (ESES). Autistic regression occurs in approximately 30% of children with autism and is associated with an epileptiform EEG in approximately 20%. The behavioral phenotypes of CSWS, LKS, and autistic regression overlap. However, the differences in age of regression, degree and type of regression, and frequency of epilepsy and EEG abnormalities suggest that these are distinct phenotypes. CSWS with autistic regression is rare, as is autistic regression associated with ESES. The pathophysiology and as such the treatment implications for children with CSWS and autistic regression are distinct from those with autistic regression without CSWS.

Using the language characteristics of clinical populations to understand normal language development.

The overall purpose of this article is to describe the speech and language abilities of children who have selected clinical conditions, not only to characterize the outcomes of those conditions, but also to understand fundamental requirements for language learning in typically developing children. This developmental cognitive neuroscience analysis conceptualizes the clinical conditions as naturalistic experimental manipulations, selectively altering factors in the language-learning situation that could not otherwise be ethically manipulated in a research study.

The spectrum from BCECTS to LKS: The Rolandic EEG trait-impact on cognition.

The laboratory hallmark of BCECTS is the rolandic discharge (RD) in the EEG of patients, occurring in a characteristic topographical, vigilance-related, event-related, and age-related pattern, disappearing during puberty. RDs are present in 2% of healthy children. About 8% of children with RDs have epilepsy. An increased prevalence rate of RDs is found in children with cognitive and behavioral disorders, with headaches and some genetic syndromes. In some patients, the cognitive disorders are transient but in others they are progressive, resulting in stable mental retardation after puberty. A recent study of 36 BCECTS patients addressed the following questions. (1) the possible relationship between the severity of RDs and the neuropsychological deficits; (2) the profile of neuropsychological deficits; (3) changes of cognition related to EEG changes; and (4) effects of therapy. No correlation was found between global IQ and the severity of the RDs. All the children had at least one specific learning disorder (sometimes long-lasting). When the children were treated, a correlation between cognitive and EEG improvement could not be demonstrated. Recently, 21 patients without epilepsy but with attention deficit and hyperactivity and/or learning disorders were studied: an open treatment trial with sulthiame resulted in improved sustained and selective attention. The neurobiology of RDs and their relationship to cognitive dysfunction and epilepsy requires further study.

Epileptic encephalopathy of late childhood: Landau-Kleffner syndrome and the syndrome of continuous spikes and waves during slow-wave sleep.

Landau-Kleffner syndrome (LKS) and the syndrome of continuous spikes and waves during slow wave sleep (CSWS) are two points on the spectrum of functional childhood epileptic encephalopathies. They are characterized by a severe paroxysmal EEG disturbance that may permanently alter the critical synaptogenesis by strengthening synaptic contacts that should have been naturally "pruned." The much more common benign epilepsy with centrotemporal spikes is also related to LKS and CSWS by a common pathophysiology. Although prognosis in LKS and CSWS for seizure control is good, cognitive function declines and permanent neuropsychologic dysfunction is seen in many cases. This permanent damage is most evident in those patients who had early-onset EEG abnormality and a prolonged active phase of continuous spike-and-wave discharges during sleep. If the active phase of paroxysmal activity persists for over 2 to 3 years, even successful treatment does not resolve neuropsychologic sequelae. In LKS, the paroxysmal activity permanently affects the posterior temporal area and results in auditory agnosia and language deficits; in CSWS, the frontal lobes are more involved and other cognitive disturbances predominate. Aggressive treatment should include high-dose antiepileptic drugs, corticosteroids, and surgery in specific cases.

Acquired epileptiform aphasia: a dimensional view of Landau-Kleffner syndrome and the relation to regressive autistic spectrum disorders.

Acquired epileptiform aphasia (AEA) is characterized by deterioration in language in childhood associated with seizures or epileptiform electroencephalographic abnormalities. Despite an extensive literature, discrepancies and contradictions surround its definition and nosological boundaries. This paper reviews current conceptions of AEA and highlights variations in the aphasic disturbance, age of onset, epileptiform EEG abnormalities, temporal course, and long-term outcome. We suggest that AEA, rather than being a discrete entity, is comprised of multiple variants that have in common the features of language regression and epileptiform changes on EEG. Viewed this way, we argue that AEA can be conceptualized on a spectrum with other epileptiform neurocognitive disorders that may share pathophysiological features. The implications of this viewpoint are discussed, with emphasis on parallels between the AEA variants and regressive autistic spectrum disorders.

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.

Familial aphasic episodes: another variant of partial epilepsy with simple inheritance?

We report on a family having partial epilepsy with simple inheritance. The affected members commonly have aphasic episodes with secondary generalization; onset occurred either in adolescence or adulthood. Patients' response to medication has varied greatly. No neurological defects or decline in intelligence were found. The case represents another variety of rare familial partial epilepsy with neocortical epilepsy features.