Landau-Kleffner Syndrome

What Causes Landau-Kleffner Syndrome?

Scientists don’t know what causes Landau-Kleffner syndrome. A small number of cases have been associated with abnormal changes (mutations) in the GRIN2A gene, and some researchers suspect that other genes, such as the  RELN, BSN, EPHB2, and NID2 genes, may be involved as well.

In some cases, children with LKS have responded well to medications used to suppress the immune system. This has led some scientists to suspect that LKS might be an autoimmune disorder in which the immune system mistakenly attacks the body’s own healthy cells.

Is Landau-Kleffner Syndrome Hereditary?

In cases where LKS is associated with mutations of the GRIN2A gene, the disorder may be inherited. These cases appear to be inherited in an autosomal dominant pattern, meaning that a child can develop the condition if they inherit the mutation from even one of their parents.

A parent with the GRIN2A mutation has a 50 percent chance of passing the mutation to each of their children. However, children with the mutation will not necessarily develop symptoms of the disorder.

How Is Landau-Kleffner Syndrome Detected?

Early detection of LKS can be difficult because children usually develop normally before symptoms of the disorder begin to emerge. When symptoms do occur, they typically first manifest as a failure to respond to verbal communication. Parents often interpret the lack of responsiveness as a sign of deafness or hearing impairment.

As symptoms progress, LKS may still be misdiagnosed as one of many other disorders with similar symptoms, including:

• Autism
• Hyperactivity/attention-deficit disorder (ADHD)
• Pervasive developmental disorder (PDD)
• Schizophrenia
• Auditory/verbal processing disorder
• Learning disorders

How Is Landau-Kleffner Syndrome Diagnosed?

Doctors may suspect Landau-Kleffner syndrome when a child has an unexplained loss of language skills. A definitive diagnosis of LKS requires that the child show an abnormal pattern of brain-wave activity, especially during periods of non-REM sleep. The diagnostic process typically includes steps to identify this brain-wave pattern and rule out other possible causes of the symptoms.

Common diagnostic steps include:

• Electroencephalogram (EEG) to measure the brain’s electrical activity
• Imaging scans such as magnetic resonance imaging (MRI) or computerized tomography (CT) to rule out brain malformations or damage
• Hearing tests to rule out hearing impairment
• Speech and language processing tests

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Landau-Kleffner Syndrome Treated?

Landau-Kleffner syndrome has no cure. The most common treatments focus on controlling seizures and brain-activity abnormalities. Other therapies may be used to help rebuild language skills. Treatment options include:

• Anti-seizure drugs such as Divalproex, ethosuximide, levetiracetam, and benzodiazepines
• Steroids such as prednisone
• Surgery (multiple subpial transection). This surgery has been used to treat children who have not responded well to other treatments. Its effectiveness is still being evaluated.
• Speech therapy
• Alternative communication devices
• Ketogenic diet

How Does Landau-Kleffner Syndrome Progress?

The progression and severity of LKS vary widely from case to case. Some children have severe and permanent loss of language abilities. Others are only mildly or temporarily affected. In cases where children regain their language skills, recovery may take years. In some cases, symptoms go away but reappear later. Seizures and abnormal brain-wave activity typically resolve by the time the child reaches adulthood.

Children with the best chance of recovery are those whose symptoms emerged later, after age six. Early intervention with speech therapy also appears to improve outcomes.

How Is Landau-Kleffner Syndrome Prevented?

Because the cause of Landau-Kleffner syndrome is unknown, there is no known way to prevent the disorder. People who have LKS, have a child with the condition, or have a family history of the disorder are at increased risk for having another child with LKS. A genetic counselor can help assess the risk for parents who are considering having more children.

Landau-Kleffner Syndrome Caregiver Tips

• Be involved with your child’s medical care. LKS is a little-understood disorder, and potential new treatments are regularly emerging. Learn all you can about the condition so you can be an active participant in your child’s care.
• Don’t give up hope. Effective treatments and early intervention often significantly improve a child’s chance of overcoming the language challenges of LKS. Improvement takes time, however, so don’t be discouraged.
• Find others who share your family’s experiences. Online support groups are important sources of news, information, and support from people who know what you’re going through.

Some people with LKS also suffer from other brain and mental health-related issues, a situation called co-morbidity. Here are a few of the disorders commonly associated with LKS:

• Anxiety and depression are common in people with LKS.
• Sleep disorders are sometimes associated with LKS.
• LKS is often associated with behaviors that resemble attention-deficit/hyperactivity disorder (ADHD).

Landau-Kleffner Syndrome Brain Science

LKS impacts the parts of the brain that control speech comprehension; children with the disorder tend to have more difficulties with language comprehension than with language expression.

Scientists are trying to understand how brain-wave activity abnormalities in LKS patients relate to the language-deficit symptoms. In many cases, LKS patients experience abnormal spikes in brain activity almost constantly during their non-REM sleep. Some scientists believe that these spikes interfere with memory formation and impair the child’s ability to remember the meaning of words.

However, treatments that successfully control abnormal brain activity don’t always result in language improvements. This leads some scientists to believe that abnormal brain activity and language symptoms are both caused by another underlying condition.

Landau-Kleffner Syndrome Research

Title:  A Novel Treatment for Aphasia and Apraxia of Speech: Measurement of Outcomes

Stage: Completed

Contact: Julie L. Wambaugh, PhD

VA Salt Lake City Health Care System

Salt Lake City, UT

To determine if speech-language therapy has a positive effect, reliable measurement tools are required to document outcomes. Currently, there is very limited information concerning the measurement of changes in speech production as a result of treatment for acquired apraxia of speech and aphasia. This study will obtain information concerning the reliability of several speech production measures over time. Thirty persons with chronic aphasia and apraxia of speech will be asked to provide speech samples in response to commonly used assessment tools on three sampling occasions so that the stability of measurements may be examined.

After establishing appropriate outcome measures, a small pilot treatment study will be conducted with four participants. The participants will receive a new treatment for aphasia and acquired apraxia of speech, and outcomes will be measured relative to speech and language production.  

Title: Timing of Transcranial Direct Current Stimulation (tDCS) Combined With Speech and Language Therapy (SLT)

Stage: Recruiting

Contact: Leora Cherney, PhD

Shirley Ryan AbilityLab

Chicago, IL

Aphasia is an acquired (typically left-hemisphere) multi-modality disturbance of language that impacts around 2 million people in the USA. Aphasia impacts language production and comprehension as well as reading and writing. The ramifications of aphasia extend beyond language impairment to negatively impacting a person’s social, vocational, and recreational activities. Currently, the most effective way to treat aphasia is with speech-language therapy (SLT). However, even if SLT is intensive, persons with aphasia are left with residual language delays. Recent research suggests pairing SLT with transcranial direct current stimulation (tDCS), a non-invasive, safe, low-cost form of brain stimulation, may aid language recovery in persons with aphasia. However, results from tDCS studies are inconclusive. The success of tDCS in combination with SLT could depend on the timing of tDCS since tDCS-induced effects depend on the neuronal state of the brain networks at the time of the stimulation. In this study, the differential impact of tDCS before behavioral SLT (offline-before therapy), tDCS after SLT (offline-after therapy), and tDCS concurrently with SLT (online) on functional language recovery in persons with aphasia will be investigated. Sham tDCS (i.e., SLT alone) as a control group will also be included in the study. The investigators hypothesize that both offline and online tDCS will improve language functioning than sham tDCS.

Title: Effects of rTMS on Brain Activation in Aphasia

Stage: Completed

Contact: Michelle L. Gravier, PhD

VA Pittsburgh Healthcare System University Drive Division

Pittsburgh, PA

This study will investigate the use of repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation method, to improve word-finding abilities in Veterans and non-Veterans with chronic language problems following stroke (aphasia). Improving word-finding is important because word-finding difficulties are among the most common and debilitating consequences of aphasia. Although rTMS has shown promise as a treatment approach, not all individuals with aphasia exhibit the same level of benefit. Specifically, this study will use functional magnetic resonance imaging (fMRI) to examine whether the likelihood of improved word-finding abilities following rTMS depends on pre-intervention language-related brain activity and will examine changes in brain activity in response to stimulation. A better understanding of how and for whom rTMS works will 1) help identify the best candidates for rTMS treatment, 2) optimize rTMS treatment protocols to improve patient outcomes, and 3) improve the investigators’ understanding of how the brain re-organizes language functions following stroke.