Am J Electroneurodiagnostic Technoi

50:122-132, 2010
ASET, Missouri

Landau-Kleffner Syndrome (LKS):

A Rare Childhood Neurological Syndrome
Carmen R. Malvestio
student
Neurodiagnostic Technology Program
Orange Coast College
Costa Mesa, California

ABSTRACT. Landau-Klejfner Syndrome (LKS) is an uncommon

condition in which a child bet^veen the ages of 3 to 9 years loses the
ability to speak and understand speech. These children may also have
autistic-tike behavior. This condition is accompanied bv an abnormal
EEG with epileptiform discharges generally in the dominant hemisphere
in the .speech areas of ihe brain. LKS tisually evolves into electrical
status epilepticus during sleep (ESES) characterized by continuous spike
md wave activity in the majority of non-rapid eye movement (non-REM)
sleep. The outcome of this syndrome varies according to the onset of the
disease. The epileptic aspect of Landau-Klejfner Syndrome is treated
with antiepileptic medication and sometimes surgery; and the speech
disability is treated with intensive language therapy. The success of each
treatment is dependent on the age and advancement of the disease and
varies with each patient.
KEY WORDS. Acquired epileptiform aphasia, aphasia, autism,
continuous spike and wake during slow wave sleep (CSWS), electrographic status epilepticus during sleep (ESES), Umdau-Kleffner
Syndrome (LKS). multiple subpial transactions.

INTRODUCTION
Landau-Kleffner Syndrome (LKS). also known as Aphasia-Convulsion Syndrome
or Acquired Epileptiform Aphasia, is a rare childhood neurological disorder. LKS is
characterized by a sudden or gradual inability to understand or express language
Received: December 10. 2009. Accepted for publication: February 8. 2010.
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(aphasia) and an abnormal EEG with myoclonus and brief absence-like attacks. LKS
affects Broca's area and Wernicke's area, which are the parts of ihe bruin that control
speech and comprehension respectively. The first manifestation of the language
problem is often word deafness or auditory verbal agnosia, including lack of recognition of familiar noises such as whistles, bells, barking of a dog. or a ringing phone.
The appearance of this syndrome occurs during a critical period of language acquisition. Speech production is affected just as badly as or even worse than language
comprehension.
WHO GETS LKS?
This rare syndrome usually occurs in children between the ages of 3 and 9 years.
with a mean age of 5 to 7 years. However, symptom onset has been described in
patients as young as 18 months and in those as old as 13 years. In LKS there is a
slight male predominance of an approximately 2:1 ratio and about 12% of patients
have a family history of epilepsy. The prevalence of LKS is I per 1000 children
(Chiolalo et al. 2003).
CLINICAL MANIFESTATIONS
The first manifestation is language deterioration which commonly occurs over
weeks or months, but acute onset after a seizure has also been described (Sotero
de Menezes 2007). Parents report that the child develops agnosia or word deafness
and the child no longer responds to commands, even with raised voices. Auditory
agnosia, or receptive dysfunction, is the dominant manifestation in the early stages of
this syndrome. Some parents or doctors assume at first that the child has lost his/her
hearing. The condition sometimes deteriorates until total unresponsiveness and
impaired speech or mutism is reached. Some patients first develop some type of
language disturbance prior to acquired aphasia. Verbal expression is marked by a
gradual increased in misarticulation. usage of wrong words, or the wrong combination of words and fluent jargon. The child may express himself with a sign language
system, gestures, or writing which may be relatively preserved.
The changes in the patient's speech with this syndrome may be due to disruptions
of the normal connections ora reaction of the speech area of the brain to the continuous epileptiform discharges. However, the severity of the aphasia does not always go
hand and hand with the degree of EEG abnormality (Sotero de Menezes 2007).
Some affected children have seizures and some do not: therefore, this syndrome
is also sometimes misdiagnosed as pervasive developmental disorder, hearing
impairment, learning disability, auditory/verba I processing disorder, attention dellcil
disorder, mental retardation, childhood schizophrenia, or emotional/behavioral
problems (NINDS 2008).

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The child may develop neuropsychological symptoms and the child's intelligent
quotient (I.Q.) tnay be adversely affected. Hyperactivity and decreased attention
span are common in LKS. Behavioral disturbances are seen in as many as 78% of the
patients (Sotero de Menezes 2007). Although behavior patterns are secondary to the
language impairtiient. some patients may have complex, bizarre, and aggressive
behaviors which include hyperactivity, excitability, psychosis, and attention deftcit.
These conditions may become so severe that the child cannot function normally.
The aggression and rage tnay be so protninent that the parents may take the child to
a psychiatric service rather than a neurological service.

AUTISM vs. LKS

The child usually develops speech normally prior to onset of LKS. This can lead
to a mistaken diagnosis of autism, as the onset is very similar. Autistic children
have communication deficits and show abnormal development of spoken language.
Autistic chiidren experience language regression in as many as 39% of cases,
especially children with low cognitive function (Sotero de Menezes 2007). Autistic
children are unable to initiate or sustain a conversation. Their language is often
repetitive, stereotyped, and idiosynctatic with meaningless expressions. Sotne but
not all patients with LKS have seizures, and some patients with autism may have
EEG abnormalities with or without seizures. The relationship of language regression,
epilepsy, epileptiform EEG activity, and autistii is not understood in its entirety and
is still under study. In a study of auti.stic children of whom 60% had an EEG study,
about 22% had epileptiform abnormalities. In approximately one half of these
children, the discharges were located over the centrotemporal region, regardless of
whether the child had seizures or had speech regression (Sotero de Menezes 2007).
While there are comnionulities in both conditions, sotne differences also arise. The
great majority of children with autism who undergo language regression do so before
three years of age (Pearl et al. 2001). versus a mean age of language regression
in LKS of 5 to 7 years. Only 10% of children with LKS regress before three years
(Pearl et al. 2001 ). Since speech and language is more developed in older children,
the changes that occur with LKS are tnore drastic than in the case of autistic children
who only experience the loss of single words.
OTHER DIAGNOSES vs. LKS
There are several sitnilar behaviors, symptoms, or characteristics seen in other
causes of aphasia and careful differentiation should be tnade in order to render the
cotrect diagnosis. Head trauma, brain tumors, stroke, brain neoplasms, increased
intracrania] pressure, or neurocysticercosis can be associated with aphasia in

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children. Therefore, imaging studies such as magnetic resonance imaging (MRI)

should be used to clarify the diagnosis.
Deaf children may also have symptoms similar to LKS. Deaf children may
gradually loose the ability to speak or understand speech and often an audiological
evaluation is necessary.
Patients with LKS show symptoms of decreased attention span, aggressive
behavior, rage attacks, psychotic behavior, and hyperactivity. Sitnilar or the same
symptoms are seen in children suffering from attention deficit hyperactivity disorder
(ADHD).
Children with neurodegenerative diseases, such as adrenoleukodystrophy may
complain of difficulty in processing auditory information and language comprehension due to the dysmyciinalion of the white matter in the tempt)toparietal region. The
onset of this particular rare disease is similar to patients with LKS. This disease also
affects primarily males as in the case of LKS.
Because of ail the symptoms and clinical manifestations mentioned above, the
differentiation of LKS from other syndromes or diseases is quite difficult; especially
in cases where the patient has not had a seizure or an abnormal EEG. It can also
be difficult to diagnose in cases where an epileptiform EEG might be missed or
misdiagnosed.

CAUSES of LKS
As is the case with matiy types of epilepsies and epileptic syndromes, the etiology
of LKS is still unknown. LKS may be as.sociated with underlying problems in
the speech area of the cerebral cortex, caused by subacuie bitemporal encephalitis,
congenital malformations, cysts, or brain tumors (Sotero de Menezes 2007). Other
etiologies include a genetic predisposition, toxoplasmosis. neurocysticercosis,
temporal astrocytoma. lempotal ganglioglioma, hemophilus influen/ac meningitis,
subacute sclerosing panencephalitis. inllammatory demyelinating disease, and
abnormal zinc metabolism (Pearl et al. 2001 ). There is a single report that depicts
LKS in a child wiih neurocysticercosis (Pellock et al. 2001 J.

EEG FINDINGS IN LKS

LKS is initially characterized by an EEG pattern of paroxysmal activity predominantly in the temporal (language dominant) or parieto-occipital regions during
the awake state. The interictal sleep pattern typical of LKS is characterized by
electrographic status epilepticus during sleep (ESES) of unusually high voltage
(Niedermeyer 1999). The .spike and wave complex is a slow pattern in the range of
2 to 2.5 Hz. occurring for more than 857r of slow wave sleep (Figures 1. 2, and 3).

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LKS

FIG. 1. EEG of a 9-year-old female with history of language regression. EEG sample
shows generalized 2 Hz spike and wave activity during non-rapid eye movement
(non-REM) sleep; electrographic status epilepticus during sleep (ESES). Timebase = 1
second indicated by black thick horizontal line.

William Landau and Frank Kleffner (1957) were die first to suggest that a correlation
between paroxysmal discharges and language deterioration existed, and reported five
children with acquired aphasia associated with a convulsive di.sorder. These children
exhibited "normal acquisition of speech" followed by aphasia, seizures, and EEG
abtiormalities. Over 200 cases have been reported since 1957 (Pellock et al. 2001 ).
Childten who develop seiztires, usually develop generalized or focal motor seizures soon after speech is lost. Seizures can occur in approximately liWc of patients
but usually are infrequent (Pellock et al. 2001). After 10 years of age, only one fifth
of patients continue to have sporadic seizures; by 15 years of age. seizures rarely
persist (Pearl et al. 2001 ). Seizures generally disappear by adulthood.
Partial motor seizures oecur more often during the night. Less frequently the
seizures are generalized tonic-clonic seizures, atypical absence.s. or myoclonicastatic seizures. Cotnplex partial seizures with automatisms are not common. Some
children appear to have worsened language skills during the periods of increased
epileptiform activity.

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127

FIG. 2. EEG of a 5-year-old boy with history of language regression. EEG sample shows
generalized 2 Hz spike and wave activity during non-rapid eye movement (non-REM)
sleep; electrographic status epilepticus during sleep (ESES). Sensitivity = 30 |jV/mm;
timebase = 1 second indicated by black thick horizontal line.

The EEG epileptiform activity varies. Some of the patterns seen arc bilaleral.
independent temporal or temporoparietal spikes; bilateral temporal I to 3 Hz slow
waves; generalized sharp nr slow wave discharges; and multifociil or unilateral
spikes. Background activity is generally normal. Epiteptifbrm activity is activated
mainly by sleep, especially sleep onset. Hyperventilation and pbotic stimulation are
seldom activators of epileptiform activity in LKS.
Since in about 85% of LKS patients the high voltage spike and wave activity
occurs during non-rapid eye movement (non-REM) sleep and decreases in intensity
during REM sleep, long-term EEG monitoring is often necessary to detect this
syndrome.
In the eariy stages of this syndrome, the high voltage epileptiform activity may
appear only when tbe patient is asleep. As the syndrome progresses, the epileptiform
activity may be seen sporadically in the waking state as spike and wave or multifocal
spikes in addition to the continuous spike-wave bursts during sleep.

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FIG. 3. This is an EEG record of an 8-year-old female with partial seizures, epileptic aphasia, and language regression. EEG sample shows generalized spike and wave discharges
from 1 to 3 Hz during non-rapid eye movement (non-REM) sleep; electrographic status
epilepticus during sleep (ESES). Timebase = 1 second indicated by black thick horizontal
line.

OTHER DIAGNOSTIC TESTS

Evoked potential studies have been performed on a variety of language and hearing disorders to determine the pathophysiology. Auditory evoked potentials (AEP)
tests performed in children with LKS have shown normal auditory brainstem and
middle latency responses. However, some tests have shown P300 potentials to be
abnormal in patients with this syndrome (Sotero de Menezes 2007).
MRI is used in patients suspected of LKS to rule out the presence of cerebrovascular thromboembolism. brain tumors, demyelinations. neurodegenerative disease,
and central nervous system (CNS) infections. Computed tomography (CT) and MRIs
performed in patients with LKS have reported to be normal (Sotero de Menezes
2007).
Positron emission tomography (PET), which shows the brain's metabolism after
the injection of a radioactive isotope, has shown a decreased metabolism in one or

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both temporal lobes during the Interjetai state. HypermetaboHstn has been present
dttring the ictal pattern of continuous spike and wave of slow wave sleep. The hypometabolism in patients with LKS is more prominent in tbe area of the midtemporal
gyrus on the left side of the brain (Sotero de Mene/es 2007).
Magnetocncephalography (MEG) tneasures the tnagnetic variations produced by
the electric currents of the brain. The electrical generators produce a magnetic field
that goes in and out of the scalp around the axis of a vertical dipole. In 1991. Paetau
et ai. demonstrated that MEG shows a vertical dipole in patients with LKS located in
tbe superior surface of the temporal lobe that is two to three cm deep. This type of
dipole may not be detected by an EEG. MEG is not commonly used for LKS because
is not widely available and its high cost.

TREATMENT OPTIONS
Landau-Kleffner Syndrome is very rare and the prognosis varies. There have been
very few clinical trials to study the efficacy of various treatment options. The control
of the seizures is usually not difftcult because the seizures can be successfully treated
with antiepileptic medications. However, these drugs are not often effective against
the language disorder. An improvement in the EEG may not be accompanied by
a change in aphasia. Aphasia cotitinues into adulthood despite the contR)l oi the
seizures. Antiepileptic drugs that have proven effective in controlling the seizures are
latiiotrigine. levetiracetam. valproate. and dia/epain (Hwang et al. 200-'^). Coi1costeroids have also shown efficacy in the suppressioti of seizures, improving the EEG,
and improving language when used in the eariy stages of the syndrome. In a pharmacological study of five cases. Marescaux et al. (1990) observed that soine drugs
were ineffective and even aggravating. Carbamazepine and phenytoin appeated to
increase the duration of spike-wave activity in sleep and phnobarbital intensified the
behavioral problems in patients.
Another treattnent option involves surgery. Temporal lobectotny has been used
to improve language and seizure control. Eor patients who cannot safely undergo a
lobectomy. the alternative procedure is called multiple subpial transections (Morrell
et al. 1998). This involves multiple selective shallow cuts or transections into the
cerebral cortex with minimal injury to vertically oriented cortical columns. These
cuts are done to interrupt the pathways that connect neighboring parts of the brain.
The connecting fibers causing the abnortiial electrical brain activity are severed.
Aside from the possibility of bleeding, major complications are rare and the procedure is generally well-tolerated. Due to the rarity of this disease, the appropriate
timing for this procedure and it.s long-term ramifications are still unknown and being
studied.
After seizures are controlled by either antiepileptic tnedications or surgery.
the child may need special assistance with cotiimunication. Some techniques may

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LKS

include, a one-to-one helper in the classroom to aid with understanding and presenting information, the use of sign language, color coding, visual cues, specialized
computer programs, and, most important, speech language therapy. Patients with
LKS may be able to read and write, therefore, these skills should be used for teaching
and cummunicating with the child whenever possible. The learning of sign language
not only aids in communication with the child, but diminishes anxiety and improves
social skills. The use of sign language does not prevent or delay the recovery of aphasia in patients with LKS. Due to the inability to understand or express language.
children experience frustration. This frustration may lead to disruptive behavior.
The introduction of effective communication and speech therapy can assist in alleviating such negative behavior. Speech therapy should be started early in order to
regain as much language ability as possible.

PROGNOSIS
The prognosis for children affected by LKS has several variables. Outcomes range
from complete recovery after several months or years to permanent severe language
impairment. However, some patients experience improvement with only residual
moderate language deficits. A relationship between the onset of the syndrome
and the ability to regain language has been observed. Since younger children have
not developed sufficient language skills, those four years of age and younger have
demonstrated worse outcomes in language ability. When the onset of LKS is after six
years of age and when speech therapy is started early, the prognosis is improved and
the result of the syndrome is less severe. But the speech and comprehension ability
may not return to normal levels for the age of the child. In some cases remission
and relapse may occur. The prognosis is also dependent on how severe the EEG
disturbances were, how long the epileptiform activity continued, and the location
of the abnormal activity. A long-term study of 11 patients with a mean follow up of
nine years, revealed complete language recovery in only 18.2% of cases and mental
retardation in 63.6% (Peari et al. 2001 ).
The indicators of a favorable prognosis are onset of symptoms after six years of
age and early speech therapy (Pellock et al. 2001 ).

CONCLUSION
Landau-Kleffner Syndrome, characterized by acquired aphasia and an abnormal
EEG pattern of focal or multifocal epileptic discharges during non-REM sleep, is
still considered a rare and idiopathic syndrome. Due to the variations in outcomes,
similarities with autism, manifestations, and progress of the disorder, this syndrome
is sometimes difficult to diagnose and treat. A positive outcome greatly depends
on how early LKS is recognized and treated, but unfortunately a large percent of
childien are left with language deficits.

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ACKNOWLEDGEMENT
I would like to thank Walt Banoczi, program director of Neurodiagnostic
Technology of Orange Coast College. Costa Mesa for his guidance, encouragement,
and support in the preparation of this article. His contributions to the field of
Neurodiagnostics and his dedication to the education of future technologists have
proveti to be key factors in the success of the profession.
I would like to extend a thank you to Conrad Szeliga at UCLA Medical Center
Neutophysiology Department for his contribution to this article.
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