Landau Kleffner Syndrome

Landau Kleffner Syndrome

M.A. Mikati , ... A.N. Shamseddine , in Encyclopedia of Neuroscience, 2009

Landau–Kleffner syndrome (LKS) is an acquired epileptic aphasia in which children 3–8   years old, who already have developed normal speech, experience language regression with verbal auditory agnosia, abnormal epileptiform activity, and behavioral disturbances. Its pathophysiology involves synchronization, presumably through thalamic-related neuronal networks, of epileptiform activity in speech areas leading to marked discharge activation in sleep. There are no controlled studies of LKS therapy. Current treatment protocols usually include steroids or valproate as well as older and newer antiepileptic drugs. Emerging therapies include high-dose diazepam, intravenous gammaglobulin, and multiple subpial transection.

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Neuroinflammation in the Pathogenesis of Early Life Epileptic Encephalopathies

Seda Salar PhD , Aristea S. Galanopoulou MD, PhD , in Acute Encephalopathy and Encephalitis in Infancy and Its Related Disorders, 2018

Landau-Kleffner Syndrome/Continuous Spike Waves in Sleep

LKS 147 and CSWS 148 manifest language or cognitive and behavioral regression, respectively, in response to the appearance of epileptic discharges in the EEG of the patients. 4–6,11 ACTH and/or corticosteroids are considered as a treatment option 125 and may improve both EEG and language or neurodevelopmental deficits.

No animal model for these types of EE has been developed. 9 Although mutations in glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) are suggested to be involved in the pathology, 126 autoimmune pathology is also considered for LKS. 72 Autoantibodies against both central and peripheral myelin are detected in three LKS patients during the time when speech exacerbation is observed where steroid treatment normalizes this autoimmune reaction in the same patients. 127 Antibodies against brain endothelial cells are present in serum of patients with LKS variant (LKSV) disease, LKS involving abnormalities in social skills (autism-like phenotype). 128 Autoantibodies against cerebellum, auditory cortex layer V, and brainstem are also observed in serum from patients with LKS/LKSV and CSWS. 129

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Sleep and Epilepsy

Sudhansu Chokroverty , Pasquale Montagna , in Sleep Disorders Medicine (Third Edition), 2009

Landau-Kleffner Syndrome

Landau-Kleffner syndrome (LKS) is an acquired aphasic syndrome occurring in a previously normal child and probably is a variant of CSWS. 181 The characteristic language dysfunction in LKS is an apparent "word deafness" or auditory verbal agnosia. There are many similarities between CSWS and LKS, and the type of neuropsychological dysfunction may depend on the location of the discharge (e.g., frontal in CSWS and temporal in LKS). Most CSWS patients have no evidence of language dysfunction. Approximately 70–80% of children have seizures that are characterized by eye blinking, head dropping, or minor automatisms with secondary generalization. These patients respond to antiepileptic medications and remain seizure free by the mid-teens. The EEG pattern is similar to that noted in CSWS.

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Acquired Epileptiform Aphasia or Landau–Kleffner Syndrome: Clinical and Linguistic Aspects

GIANFRANCO DENES , in Handbook of the Neuroscience of Language, 2008

35.4. THE SPECTRUM OF REGRESSIVE LANGUAGE DISORDERS AND EPILEPSY

LK syndrome is not the only developmental disorder combining EEG abnormalities and language regression. In a review of the syndrome, Stefanatos et al. (2002) list a number of developmental neurocognitive epileptiform disorders that are associated with speech and language deterioration (see Table 35.1). It is therefore not surprising to find discrepancies in the definitions of the clinical characteristics and nosological boundaries between LK and other related disorders. Among the latter, of particular relevance is autistic regression, that is, a disorder surfacing in the first or second year of life after normal development and characterized by a loss of social and emotional reciprocity, language and non verbal communicative disorders, and stereotyped behavior. The etiology is still unknown, neither metabolic nor structural abnormalities have been detected.

Table 35.1. Summary of Epileptiform Neurodegenerative Disorders that are Linked with Speech/Language Deterioration in Children

Epileptiform neurodegenerative disorders Receptive language Expressive language/speech Cognitive Social Behavior Reference
Autistic regression (with epileptiform EEG) + + (+)+ +++ ++ (+) ++ (+) ++ (+) Nass and Devinsky(1999)
Childhood disintegrative disorder (with epileptiform EEG) + + + +++ +++ ++ (+) ++ (+) Kurita et al. (1992)
Continuous spike andwave during slow wave sleepsyndrome + + + +++ +++ ++ (+) ++ (+) De Negri (1997)
Acquired epileptiform aphasia + + + + + (+) (+) (+) + (+) Landau andKleffner (1957)
Congenital aphasia (with epileptiform EEG) + (+) ++ (+) (+) (+) (+) McKinney andMcGreal (1974)
Acquired opercular syndrome — +++ (+) ? ? Shafrir and Prensky(1995)
Atypical benign partial epilepsy (+) ++ (+) (+) (+) Hahn et al. (2001)

Note: Extent of impairment: + ++severe, ++moderate, +mild, –normal to borderline, (+)variable, ?insufficient information. The severity ratings are estimates used here for illustrative purpose only to convey relative similarities and divergences between conditions. These conditions are extremely variable so there exception to the depicted patterns. References provide relevant case material.

Source: Stefanatos, G.A., Kinsbourne, M., & Wasserstein J. (2002). Acquired epileptiform aphasia: A dimensional view of Landau-Kleffner syndrome and the relation to regressive autistic spectrum disorders. Child Neuropsychology, 8(3), 195–228.

Autistic regression is part of the autistic spectrum disorder, a broad category which includes the various types of pervasive developmental disorders according to the Diagnostic and Statistic Manual of Mental Disorders (American Psychiatric Association, 1994). Abnormal EEG findings, with or without epileptic seizures, have been documented in a consistent minority of children affected by autistic regression. Given the number of shared characteristics of the two syndromes, a quest for defining the differential diagnostic criteria appears particularly difficult. In a few of the large scale studies on the autistic spectrum disorders, Kurita et al. (1992) found that in general language and speech were lost before the age of 30 months in autistic regression, while in LK children the onset is usually at 3–4 years of age, when language has already developed significantly. Another distinguishing criterion is found in the topographic abnormalities of the EEG: while in LK syndrome the epileptiform activity is mostly centered in the language-related temporal cortices, in autistic regression the abnormalities are widespread, affecting the entire cerebral cortex. Furthermore, nonverbal cognitive abilities are usually spared in LK syndrome while there is a general decline in autistic regression and autistic spectrum disorders. Finally, from a behavioral point of view, of paramount importance is that in most LK children the display of affection is preserved (Landau & Kleffner, 1957), although some of them can display persistent autistic traits (Rossi et al., 1999).

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Magnetoencephalography in Epilepsy

Robert C. Knowlton , William W. Sutherling , in Magnetic Resonance in Epilepsy (Second Edition), 2005

Landau–Kleffner Syndrome

Landau–Kleffner syndrome (LKS) represents a unique and challenging epilepsy syndrome that may particularly benefit from MEG spike localization. LKS is an acquired epileptic aphasia or verbal agnosia occurring in a previously normal child, characterized by deterioration in language function in association with a seizure disorder and/or a paroxysmal EEG abnormality (66). The signature EEG abnormality is characterized by very frequent large-amplitude epileptiform discharges recorded with EEG in wide and varied distributions but mainly over the centrotemporal regions of either hemisphere. MEG studies in LKS patients have shown that the primary sources for the epileptiform disturbances lie predominantly in intra-sylvian cortex (67, 68).

Figure 16.7 is an example of MEG localization of very widespread typical epileptiform disturbances in a child with classic LKS. In spite of the large field, and even bilateral distribution (left-sided amplitude maximum), the source estimates based on MEG are remarkably unifocal and clustered tightly in the intrasylvian cortex. Extrasylvian sources appear to be secondary (from both cortico–cortical and transcallosal spread) when spatiotemporal analysis is performed (67). EEG detection and ability to localize deep fissural sources is limited compared to MEG because of overlapping secondary activation of radial sources in perisylvian convexity cortex. This activity in effect acts as noise, compromising the detection and optimal characterization of the intrasylvian sources where over two-thirds of the regional cortical mantle lies.

FIG. 16.7. MEG spike localization in Landau–Kleffner syndrome. A. EEG of patient's typical, almost continuous spikes and spike–slow-wave discharges recorded during sleep; discharges are widespread but consistently maximal over the left hemisphere. B. MEG spike dipole source estimates (yellow triangles; tails represent dipole vectors; circle represents a typical 95% confidence volume from a selected spike source) for those discharges seen on EEG are tightly localized to a relatively focal region in the deep left intrasylvian cortex.

One practical and important clinical consideration surrounding LKS source localization is the influence it may have on surgical treatment. Intra- and perisylvian multiple subpial transections can abolish the spikes (including secondary extrasylvian sources) and result in rapid reacquisition of language and speech function (67). The first challenge in LKS cases is to determine whether a predominant single source exists for what often appears on EEG to be widely distributed and bisynchronous. The second challenge (if a single unilateral source is strongly suspected) is to determine the location and extent of the critical sources. Both are crucial in surgical decision making – the former to determine who are best candidates for surgery and the latter to aid in minimizing risk (limiting as much as possible the opening of the sylvian tissue) and optimizing the likelihood that the correct location will be targeted.

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Epilepsy, Sleep, and Sleep Disorders

Milena K. Pavlova , Sanjeev V. Kothare , in Principles and Practice of Sleep Medicine (Sixth Edition), 2017

Landau-Kleffner Syndrome

Landau-Kleffner syndrome (LKS) is an acquired disorder with epileptic aphasia in which children, usually 3 to 8 years of age and who have developed age-appropriate speech, experience language regression with verbal auditory agnosia, epileptiform activity during sleep, behavioral disturbances, and sometimes overt seizures, more often in sleep. 7 Seizures arise out of sleep (focal clonic, atypical absences) and are less frequent and less severe than in ESES (absent in 20% to 30%). Behavioral problems are also less severe than in ESES.

There are several similarities between ESES and LKS. Both conditions demonstrate a normal EEG background during wakefulness, with rare focal or generalized spike wave discharges. In ESES, however, discharges during sleep are generalized, whereas in LKS, spike wave activity is mainly in the temporal channels. In ESES, epileptiform activity becomes virtually continuous during NREM sleep, such that it may be impossible to distinguish sleep stages.

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Epilepsy

Péter Halász , in Handbook of Clinical Neurology, 2012

Epileptic symptoms

LKS is a childhood disorder arising in previously normal children, characterized by the loss of language skills, acquired verbal auditory agnosia, multifocal spikes, and spike–wave discharges localized mainly over the centrotemporal regions, continuously or subcontinuously during sleep. Epileptic seizures (usually rare), behavioral disorders, and hyperkinesia are observed in about two-thirds of the patients. "The prognosis is favorable, with remission of seizures and EEG abnormalities before the age of 15 years" (Rossi et al., 1999). No evidence of associated focal brain lesions has been documented. In a recent review, Deonna and Roulet-Peret (2010, p.747) emphasized that "Landau–Kleffner is now seen as the rare and severe end of a spectrum of cognitive–behavioral symptoms that can be seen in idiopathic (genetic) focal epilepsies of childhood, the benign end being the more frequent typical rolandic epilepsy."

At an early stage of the disorder, unilateral IEDs are more common, resembling discharges seen in IFCE, localized to a wide area around the sylvian fissure. Bilateral "generalized" spike–wave discharges are also common. Later, bilateral focal discharges are prevalent in roughly homologous areas.

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Neonatal and Pediatric Electroencephalography

Jin S. Hahn , in Aminoff's Electrodiagnosis in Clinical Neurology (Sixth Edition), 2012

Acquired Epileptic Aphasia (Landau–Kleffner Syndrome)

Acquired epileptic aphasia, a disorder first described by Landau and Kleffner, is characterized by the appearance of a progressive aphasia in a previously healthy child. The degree of aphasia roughly appears to parallel the EEG abnormalities. Seizures commonly occur after the onset of the aphasia but are treated easily with antiepileptic medication. Standard antiepileptic treatment usually has no effect on the aphasia, which may improve over years but infrequently disappears completely. The etiology is unknown.

The EEG is characterized by slow spike-wave discharges that are of higher amplitude over the temporal regions and spread diffusely through both hemispheres, giving the appearance of a generalized discharge. A striking EEG abnormality often occurs during sleep, also called "continuous spikes and waves during slow sleep" or "electrical status epilepticus during slow-wave sleep." 115 This latter syndrome can occur independently of the Landau–Kleffner syndrome and is often associated with progressive cognitive and behavioral deterioration. 137–139 With neurophysiologic techniques, including invasive electrical recording and evoked potential studies, as well as radiologic procedures including positron emission tomography, the focal epileptiform disturbance can be localized to the language cortex in one temporal lobe, with evidence of spread to homologous regions of the contralateral hemisphere.

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Paroxysmal Disorders

Gerald M. Fenichel MD , in Clinical Pediatric Neurology (Sixth Edition), 2009

Diagnosis

Acquired epileptiform aphasia, as the name implies, is different from autism and hearing loss because the diagnosis requires that the child have normal language and cognitive development before the onset of symptoms and normal hearing. The EEG shows multifocal cortical spike discharges with a predilection for the temporal and parietal lobes. Involvement is bilateral in 88% of cases. An intravenous injection of diazepam may normalize the EEG and transiently improve speech, but this should not suggest that epileptiform activity causes the aphasia. Instead, both features reflect an underlying cerebral disorder. Every child with the disorder requires cranial MRI to exclude the rare possibility of a temporal lobe tumor.

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Epileptic Syndromes and Diseases

Natalio Fejerman , in Encyclopedia of the Neurological Sciences, 2003

Nosology

Landau–Kleffner syndrome (LKS) constitutes the paradigmatic example of an epileptic syndrome in which persistent clinical symptomatology (acquired auditory agnosia and aphasia) is clinically more important than seizures. The 1989 ILAE classification placed this syndrome under epilepsies and syndromes undetermined as to whether they are focal or generalized. In the same category, the syndrome of continuous spikes and waves during slow sleep was included as a definate entity. However, recently, many common features were recognized as shared by these two syndromes and questions arose regarding whether they are two distinct entities or subclasses of a single syndrome. Progressive impairment of higher cortical functions should be considered as an epiphenomenon of abnormal brain electrical activity and prompts the inclusion of these syndromes among the EEs.

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