Lennox-Gastaut syndrome: what is it, symptoms, treatment, prognosis

What is Lennox-Gastaut syndrome?

Lennox syndrome–Gastaut (SLG) is a severe form epilepsywhich usually manifests itself in infancy or early childhood. Affected children experience several different types of seizures, most commonly seizures of an atonic, tonic, and atypical nature. Children with Lennox-Gastaut syndrome can also develop cognitive dysfunction, developmental delays, and behavioral problems. SLH can be caused by many underlying conditions, but in some cases the cause cannot be identified. SLH is difficult to treat because it is resistant (immune) to many types of antiepileptic drugs. Research is ongoing to identify and evaluate new treatments for Lennox-Gastaut syndrome.

There is no consensus in the medical literature regarding the precise definition of Lennox-Gastaut syndrome. As a rule, three conclusions are required for the diagnosis: multiple generalized types of seizures; slow burst-wave pattern (less than 2.5 Hz) on the EEG; and cognitive dysfunction. The Task Force of the International Antiepileptic League (IPEL) most recently classified the disorder as epileptic encephalopathy. Epileptic encephalopathies are a group of disorders in which seizure activity leads to progressive cognitive dysfunction.

Signs and symptoms

Symptoms of Lennox-Gastaut syndrome usually begin in infancy or childhood, most often between 3 and 5 years of age. Children with SLH are affected by several types of seizures, which are mainly electrical disturbances in the brain. Most sufferers experience several types of seizures, several times during the day. As people get older, the types and frequency of seizures may change.

The most common types of seizures associated with Lennox-Gastaut syndrome are tonic and atonic seizures. Tonic seizures cause an increase in muscle tone and muscle stiffness. They are characterized by sustained muscle contractions that can cause mild disturbances such as slight bending of the body and short-term interruption of breathing, or more serious problems such as muscle spasms in the face and flexion or extension of the arms and legs. Affected children may stretch their arms over their heads like a ballerina. Tonic seizures are usually short-lived (lasting from a few seconds to a minute) and are especially common at night during sleep, but can also occur during the day. During a tonic seizure, a short-term loss of consciousness usually occurs. Tonic seizures that occur on awakening can lead to patients falling out of bed.

Atonic seizures cause sudden loss of muscle tone and lethargy. They can lead to head nodding, posture problems, or sudden falls. Atonic seizures are also known as falling seizures. Atonic seizures can lead to head and face injuries due to sudden, unexpected falls. While sitting, affected people may fall forward or backward in the lower back. Atonic seizures can only partially affect consciousness and usually last only a few seconds

The third type of seizure commonly associated with Lennox-Gastaut syndrome is atypical absences. This type of seizure is associated with a period of unconsciousness, usually marked by an indifferent gaze. Absence seizures start and end abruptly, and the affected person usually resumes activity with no memory of the episode. Absence seizures do not cause seizures and can be so mild as to go unnoticed. They usually last from a couple to a few seconds. If a child is delayed in development, parents may notice only a slight change in functioning or response.

Additional types of seizures may less commonly affect people with Lennox-Gastaut syndrome. These include myoclonic seizures, which are characterized by abnormal jerky movements and may occur alone or in combination with atypical absence seizures; tonic-clonic seizures that last a couple of minutes and are characterized by rigidity of the limbs, and then twitching of the limbs and face; and partial or focal seizures, which are associated with electrical disturbances in a limited area of ​​the brain and have various forms. Some people with Lennox-Gastaut syndrome experience prolonged, continuous seizure activity that lasts more than 30 minutes (non-convulsive (non-convulsive) status epilepticus). Non-convulsive status epilepticus may go unnoticed. BES is the most difficult diagnostic task for a neurologist, epileptologist or neuroreanimatologist.

In children with Lennox-Gastaut syndrome, intelligence is usually, but not always, impaired. Affected children may experience varying degrees of cognitive dysfunction and delays in reaching developmental milestones such as sitting, crawling, or walking. Children with SLH may develop normally before the onset of seizures and then lose previously acquired skills (psychomotor regression). Because seizures associated with Lennox-Gastaut syndrome are usually resistant to treatment, intellectual disabilities and learning problems may worsen over time. Children with SLH can also develop behavioral problems ranging from hyperactivity and irritability to autistic symptoms and psychosis.

In some cases, patients with Lennox-Gastaut syndrome may initially suffer from infantile spasms. Infantile spasms, also known as West syndromeare characterized by sudden involuntary contractions of the head, neck and trunk and / or uncontrolled extension of the legs and / or arms.

Causes and risk factors

Approximately 70-80 percent of Lennox-Gastaut syndrome patients have a definable cause. These cases can be called symptomatic Lennox-Gastaut syndrome. Examples of conditions that can cause Lennox-Gastaut syndrome include:

• abnormal development of the cerebral cortex (cortical dysplasia);
• congenital infections;
• stroke;
• head trauma;
• decreased oxygen supply that occurs before birth (perinatal hypoxia);
• central nervous system infections such as encephalitis or meningitis;
• a rare genetic disorder called tuberous sclerosis.

Approximately 17-30 percent of people with a history of SLH have West syndrome. In general, these cases tend to be more serious.

Lennox-Gastaut syndrome can also be classified as cryptogenic, in which the cause is unknown or cannot be determined upon examination. Cryptogenic cases are thought to be the result of an unidentified condition (secondary Lennox-Gastaut syndrome). Individuals with cryptogenic SLH had no prior history of seizure activity, prior neurological problems, or cognitive impairment prior to the development of the disorder. Cryptogenic cases usually have a later onset than symptomatic cases.

In some cases of Lennox-Gastaut syndrome, the comorbid condition is absent or suspected, and the cause of the disorder is unknown.

Although the cause of SLH is known in most cases, the exact mechanisms underlying the various seizures that characterize the disorder are not known. Researchers have not found any genes associated with Lennox-Gastaut syndrome, although the disorder may have a genetic component that contributes to its development. More research is needed to identify specific factors, including any potential genetic factors that are involved in the development of SLH.

Affected populations

Lennox-Gastaut syndrome affects men more often than women. SLH is estimated to occur in 0.1–28 people per 100,000 population and is believed to account for 1–4 percent of all childhood epilepsy cases. The annual incidence among children is 2 per 100,000 children. SLH usually occurs between the ages of 2-7 years, and the peak onset occurs between the ages of 3 and 5 years.

Symptomatic disorders

Symptoms of the following disorders may be similar to those of Lennox-Gastaut syndrome. Comparisons can be useful for differential diagnosis.

• West syndrome Is a type of epilepsy characterized by spasms, an abnormal brain wave pattern (interectal EEG) called hypsarrhythmia and cognitive dysfunction. The spasms that occur can range from violent movements where the whole body bends in half, or can be nothing more than slight twitching of the shoulder or eyes. These seizures usually start in the first months after birth and can sometimes go away with treatment. There are many different causes of West syndrome, and if a specific cause can be identified, a diagnosis of symptomatic West syndrome can be made. If the cause cannot be determined, a diagnosis of West Cryptogenic Syndrome is made. Some children with West syndrome may develop Lennox-Gesto syndrome.
• Epilepsy is a general term for a group of neurological disorders characterized by recurrent seizures and associated with abnormal electrical discharges in the brain. It is characterized by loss of consciousness, seizures, confusion, and disorders of the autonomic nervous system. Attacks may be preceded by an “aura,” feeling of anxiety or sensory discomfort; an aura marks the onset of a seizure in the brain. This usually occurs with partial seizures. There are many different types of epilepsy and the exact cause is unknown. Epilepsy can also occur as part of larger syndromes. Types of epilepsy or disorders associated with epilepsy include Rett syndrome, Angelman syndrome, Landau-Kleffner syndrome, Dravet syndrome and neuronal ceroid lipofuscinosis.

Diagnostics

Lennox-Gastaut syndrome is defined by the presence of a clinical triad. The triad consists of multiple seizures of different types, a characteristic EEG wave pattern (slow [1.5-2.5 Hz] pattern) (note that this pattern may not be present on every EEG.), some degree of cognitive and behavioral violations. However, these symptoms may not be present at the onset of the disease, making it difficult to accurately diagnose SLH. The wide range of possible causes of Lennox-Gastaut syndrome also complicates diagnosis.

The diagnosis of SLH is usually made on the basis of careful clinical evaluation, the patient's detailed medical history, and complete physical and neurological examination, including advanced imaging techniques such as electroencephalography (EEG) and magnetic resonance imaging tomography (MRI). During the EEG, electrical impulses from the brain are recorded. In people with SLH, this EEG test usually reveals a characteristic brain wave (slow [1.5-2.5 Hz] bursting wave). During an MRI, three-dimensional images are obtained that reflect the anatomy of the brain; such a scan helps doctors examine the structure of the brain and, possibly, determine the cause of the seizure activity.

Standard treatments

No specific therapy for Lennox-Gastaut syndrome is effective in all cases, and the disorder is particularly resistant to most treatment options. The three main forms of treatment for Lennox-Gastaut syndrome are antiepileptic drugs (AEDs), dietary therapy (usually a ketogenic diet) or apparatus / surgery (electrical stimulation of the vagus nerve or callosotomy of the body). In rare cases, resection surgery is possible.

Treatment may require a coordinated team of specialists. Pediatricians, neurologists, pediatric neurologists, surgeons, and / or other healthcare professionals may need to systematically and comprehensively plan treatment for an affected child. Families should work with healthcare providers to develop a treatment plan that covers the various potential situations, such as seizure emergencies, routine medical conditions, or what to do if the victim misses an appointment medicines. Families should also keep a list of medications that can worsen the disease. The patient's treatment regimen will need repeated revisions throughout the person's life, as the types and frequency of seizures may change, and the effectiveness of a particular therapy may decrease.

Antiepileptic drugs (AEDs) are usually given to people with Lennox-Gastaut syndrome, but individual response varies greatly. In some cases, it is possible that treatment with AED may help reduce or control various types of seizure activity associated with SLH. However, because people with Lennox-Gastaut syndrome have different types of seizures, they often require therapy with multiple types of AEDs. Such medicines may include clonazepam, sodium valproate, topiramate, lamotrigine, felbamate (under close supervision), clobazam, rufinamide, or cannabidiol. However, such medications may have limited success in treating seizure activity in some people with the disorder. In addition, AEDs can cause significant side effects, especially in people who receive many drugs in high doses. AEDs can also become less effective over time.

Valproate (valproic acid) is generally considered the first line therapy for Lennox-Gastaut syndrome because it is effective against a wide range of seizures. Valproate is usually given alone first (monotherapy), and if not effective, another drug such as lamotrigine, topiramate, rufinamide, clobazam, or cannabidiol can be added.

Additional therapies that have been used to treat people with Lennox-Gastaut syndrome include the ketogenic diet, electrostimulation of the vagus nerve, and various surgical techniques. These options are usually reserved for individuals who have been treated with at least 2-3 approved drugs without an adequate response and are usually combined with drug therapy (the exception is dietary therapy, which is usually added to drug therapy, but rarely can be successful on its own yourself).

A ketogenic diet may decrease seizure activity in some people with SLH. Ketogenic diet Is a diet high in fat and carbohydrateswhich causes the body to burn fat for energy instead of sugar (glucose). It is a strict diet that requires strict adherence and adherence. The ketogenic diet can have side effects and people on the diet should be monitored regularly by their doctors and a qualified dietitian. The effectiveness of the ketogenic diet varies greatly. Researchers don't understand why the diet is effective in treating some and ineffective in others.

Some people with Lennox-Gastaut syndrome, especially those who have not responded to other forms of therapy, can be treated with surgical methods, including complete callosotomy of the body or electrical stimulation of the vagus nerve.

Body callosotomy Is a surgical procedure in which the cerebral hemispheres are severed by cutting the corpus callosum, which is a large bundle of nerves that connects the two halves (hemispheres) of the brain and allows them to exchange information. This procedure does not involve cutting the brain tissue. This procedure is usually intended for individuals who suffer from intractable seizures that result in trauma (eg, frequent generalized tonic-clonic seizures). This therapy is most effective for atonic, tonic and tonic-clonic seizures.

Vagus nerve stimulation Is a procedure in which a device called a pulse generator is inserted into the chest and a wire runs under the skin to the vagus nerve in the neck. A pulse generator is similar to a pacemaker and transmits weak electrical impulses to the brain through the vagus nerve. These impulses prevent seizures from occurring. The intensity and time of the impulses are determined based on the needs of each person.

Forecast

Long-term prognosis is generally poor, but variable in SLH. Longitudinal studies showed that a minority of patients with SLH were eventually able to function normally, but 47-76% still had typical symptoms (mental retardation, treatment-resistant seizures) many years after onset and needed significant home).

Patients with symptomatic SLH, especially early onset, with a prior history of West syndrome, more frequent seizures or constant slow background EEG activity have a worse prognosis than patients with idiopathic attacks.

Tonic seizures may persist and become more difficult to control over time, while myoclonic and atypical manifestations are easier to control.

The characteristic diffuse slow burst of the SLH wave gradually disappears with age and is replaced by focal epileptic discharges, especially multiple independent bursts.

The mortality rate ranges from 3% (mean follow-up 8.5 years) to 7% (mean follow-up 9.7 years). Death is often associated with accidents. High injury rates are associated with atonic and / or tonic seizures.

The severity of seizures, frequent trauma, developmental delays and behavioral problems wreak havoc on even the strongest parents.