What is Landau-Kleffner Syndrome?
Landau-Kleffner syndrome (LKS) is a rare medical condition related to a person’s age that causes issues with brain functioning. It particularly impacts children’s language development and creates abnormal brainwave patterns that can be seen on an electroencephalogram (EEG), a test that measures electrical activity in the brain. These unusual patterns are most commonly focused around areas known as the temporoparietal areas.
When seizures do occur, they can take the form of ‘absence seizures’, where the person seems to “zone out,” or more noticeable ‘tonic-clonic’ episodes, which involve stiffening and shaking of the body. These generally happen more when the individual is asleep. The syndrome can also cause behavioral issues.
First identified in 1957, it’s sometimes referred to as ‘acquired aphasia with epilepsy’ in medical terminology. This name highlights the main signs of this disease: a sudden loss of language skills (aphasia) and seizures (epilepsy). While it is similar to another condition known as the continuous spike-waves during slow sleep syndrome (CSWS), these two syndromes show different symptoms and carry different diagnostic importance.
What Causes Landau-Kleffner Syndrome?
The exact cause of Landau-Kleffner syndrome (a rare and severe type of epilepsy in children), is still unknown. Brain injuries are very rarely related to this condition. However, genes may be involved. For example, the condition can be linked with changes in a certain gene named GRIN2A.
This gene makes a protein called GluN2A (also known as NR2A). This protein is part of a special receptor (like a keyhole for a key) called the NMDA glutamate-gated ion channel receptor. This is a bit like a door that lets certain chemicals in and out of our brain cells. Interestingly, NR2A is usually found in large amounts in parts of the brain that are important for speaking and understanding language. Moreover, NMDA receptors take part in many vital functions like memory and learning. Changes in the GRIN2A gene are also linked to a number of other disorders that affect a child’s development, and can involve seizures.
Some experts have also suggested that the body’s defense system, the immune system, might play a role. In some forms of epilepsy, the immune system may incorrectly attack the body’s own tissues. Researchers found higher levels of certain antibodies (proteins produced by the immune system to fight diseases) in children with Landau-Kleffner Syndrome. These antibodies were directed against a substance called BDNF, which is normally present in the brain and helps nerve cells survive and work properly.
It is also thought that an overactive or uncontrolled immune response might explain why most cases of Landau-Kleffner Syndrome get better with corticosteroids, a type of medication that can calm down the immune system.
Risk Factors and Frequency for Landau-Kleffner Syndrome
Landau-Kleffner syndrome is not very common and it’s hard to determine exactly how many people have it. It is so rare that since its identification in 1957, only a few hundred cases have been reported. Interestingly, a study in Japan discovered that about 1 in a million children have the syndrome. This condition affects boys more often than girls and is typically seen in children between the ages of 3 and 8, although it can also occur in younger children or teenagers.
- Landau-Kleffner syndrome has been reported in only a few hundred cases since its discovery in 1957.
- An estimate from Japan suggests around 1 in a million children have the condition.
- The syndrome tends to affect boys more than girls.
- It often appears in children between the ages of 3 and 8.
- However, younger children and teenagers can also be affected.
Signs and Symptoms of Landau-Kleffner Syndrome
Landau-Kleffner syndrome is a condition that typically affects children between 3 to 8 years old who have shown normal development until then. The syndrome’s main features include changes in language abilities, alterations in brain electrical activity (EEG), seizures, and behavioral disorders.
The most common feature of the syndrome is a condition called aphasia, where a child suddenly begins to have difficulty understanding and using language. This usually starts as an issue with understanding verbal speech, known as receptive aphasia, and is then followed by difficulties with speaking (expressive aphasia). The child might also start to babble, use made-up words, repeat words or phrases, or stop speaking altogether. This change typically occurs over several days, weeks, or months.
Seizures are another symptom of the syndrome, with about two-thirds of patients experiencing them. These seizures often involve partial motor seizures, generalized clonic seizures, and atypical absence seizures. Atypical absence seizures can include blinking a lot, making chewing gestures, smacking lips, or slight jerking movements of the lips.
- Aphasia, where a child has difficulty understanding and using their language
- Partial motor seizures and absence seizures, which can be characterized by sudden, brief lapses of consciousness
- Behavioral disorders such as difficulties with attention, hyperactivity, impulsivity, and distractability
- Emotional instability, anxiety, depression, sleep disorders, and sensitivity to sound
It is common for these children to also experience behavioral disorders, including issues with attention, hyperactivity, and impulsive behavior. Emotional instability, anxiety, depression, sleep disorders, memory impairment, and increased sensitivity to sound might also be seen. These symptoms can sometimes complicate the child’s clinical picture.
Testing for Landau-Kleffner Syndrome
If there’s a suspicion that a child has Landau-Kleffner syndrome, a condition that causes them to lose the ability to understand and use spoken language, the diagnosis is based on several factors. These might include the child’s medical and development history, observation of any behavioral changes, and the results of a diagnostic test called an electroencephalogram (EEG).
Doctors will look at any changes in a child’s ability to understand (receptive) or express (expressive) language. They may also notice changes in the child’s behaviour, like becoming more excitable or active than usual. To confirm the language problem isn’t due to hearing loss, an audiometric examination or hearing test will be conducted.
During this process, the child might be seen by a team of specialists coordinated by their general pediatrician. This team could include a child neuropsychiatrist, speech therapists, and motor skill experts who will conduct a thorough evaluation.
An EEG test, which shows the electrical activity of the brain, is crucial in diagnosing Landau-Kleffner syndrome. This test can show unusual activity in certain parts of the brain which handle language, especially during sleep. In some cases, these findings may reveal a condition called electrical status epilepticus during sleep (ESES). ESES is characterized by a significant increase in abnormal brain activity during sleep.
Additional evaluations may include MRI scans to identify any abnormalities in the parts of the brain responsible for language development. Detecting a decrease in volume in these areas won’t help in diagnosing Landau-Kleffner Syndrome, but it can rule out physical conditions like brain tumors.
Some genetic tests could also be useful, like analysis of the GRIN2A gene. This gene has been linked to the development of the disease in some cases. However, this is not commonly done as it is only available in some specialized centers. If a mutation is detected, it could be useful for genetic counseling, as there’s a chance that the disease might be passed on to other family members.
In some countries, testing for certain antibodies in the blood is recommended before starting treatment. These antibodies could change the way the brain functions, potentially causing conditions like Landau-Kleffner Syndrome.
Treatment Options for Landau-Kleffner Syndrome
While there’s no global agreement on the best way to treat epileptic symptoms, everyone can agree that treatment should start as soon as possible.
Epileptic Symptoms
If someone is experiencing a minor or infrequent seizure, there are several seizure medications that can help control these episodes. Commonly chosen drugs include valproate, clobazam, levetiracetam, and ethosuximide. Some medications like carbamazepine, oxcarbazepine, phenytoin, and phenobarbital are usually avoided because they can intensify the seizure-like brain activity from a condition called ESES.
Speech Therapy and Behavioral Programs
Speech therapy can help people recover their ability to speak by utilizing various strategies and communication devices geared towards vocal training. However, for younger kids who might find it hard to comply, such methods might not be effective. In these cases, a plan usually involves a psychomotor therapist at first to help with movement skills, then later accompanied by a speech therapist. Working on psychomotor skills is crucial in managing behavior and relationship struggles.
Other Treatments
Steroid medications like prednisone or prednisolone might be useful for improving or at least stabilizing language, cognition, and behavior skills. Doctors usually recommend these medications when someone’s epileptic activity and language impairments persist despite treatment. These medications can even be combined with a class of drugs called benzodiazepines.
Other treatments have been tried as well including intravenous immunoglobulin, a ketogenic diet, calcium-channel blocking drugs, and amantadine. However, results varied for these treatments.
A surgical procedure known as multiple subpial transections (MST) is another treatment option. This surgery involves cutting across horizontal brain fibers whilst leaving the vertical ones intact, with the aim of controlling epilepsy but leaving important brain areas undisturbed. Some studies have indicated that this surgery could restore language abilities in children with a disorder called Landau-Kleffner syndrome. However, other studies haven’t found significant benefits of MST compared to medical therapy. Therefore, this invasive surgery is usually limited to severe cases of epilepsy that don’t respond to medication or where steroids can’t be used due to dependency or harmful side effects.
What else can Landau-Kleffner Syndrome be?
Verbal agnosia can often be mistakenly identified as hearing loss by parents. Moreover, the behavioural issues associated with aphasia might lead to suspicion of an autistic spectrum disorder (ASD), even though regressive forms of ASD typically exhibit cognitive deficiencies in more than just language. Additionally, conditions marked by consistent inattention, hyperactivity, and impulsivity, such as attention deficit hyperactivity disorder (ADHD), may also be suspected. Therefore, it is necessary to rule out hearing loss, autism, or ADHD.
At the same time, the manifestations of epilepsy call for differential diagnosis with epileptic syndromes which are known to increase epileptiform activity during sleep, such as:
- Continuous spike-waves during slow sleep syndrome (CSWS)
- Atypical benign partial epilepsy (ABPE)
- Early-onset benign partial epilepsy with occipital paroxysm (or Panayiotopoulos syndrome)
- Lennox-Gastaut syndrome
- Pseudo-Lennox syndrome
- Benign childhood epilepsy with centrotemporal spikes (BECTS) or rolandic epilepsy (RE)
Notably, conditions like LKS, CSWS, and RE are considered as a continuous spectrum of childhood epilepsies and epileptic encephalopathies, which are featured by acquired cognitive, behavioural and speech and/or language impairment. However, aside from those affected by “epileptic encephalopathies” such as CSWS, LKS, RE, and West syndrome, most children with epilepsy don’t experience any regression.
Lastly, it’s important for doctors to consider that aphasia may be the consequence of various other causes such as lesions taking up space, effects of past traumas, and infections.
What to expect with Landau-Kleffner Syndrome
The rarity of Landau-Kleffner syndrome, a type of epilepsy, makes it hard to predict how it might progress. However, it’s generally considered a benign condition, meaning it’s non-threatening to life. But, the effects on speech, known as aphasia, can vary widely.
For example, in a study of eleven children with the syndrome, only four had no issues with language as they grew into adolescence. Meanwhile, four had moderate language issues, and three had severe language impairments even after more than ten years from diagnosis.
Some patterns hint towards a better outcome such as late-onset of aphasia, a short duration of initial symptoms, and notable fluctuations in speech abilities. Although studies are limited, it appears that language abilities tend to improve with treatment and during puberty. But, a significant portion of individuals may not return completely to their pre-disease state.
When it comes to seizures, another symptom of Landau-Kleffner syndrome, the outlook is generally positive. Seizure symptoms are usually easy to control and tend to ease before adolescence.
Very importantly, treatment can be extremely helpful, especially for those with ongoing moderate language difficulties. It is particularly beneficial for those who have severe language problems persisting after adolescence.
