Lennox-Gastaut syndrome in children and adults

Multiple tonic, clonic, atonic and myoclonic seizures are the main features that characterize Lennox-Gastaut syndrome. In general, the disease is characterized by psychomotor retardation of the patient, which only worsens over time. Lennox-Gastaut syndrome is severe and no less difficult to treat.

[ 1 ]

Epidemiology

The incidence of Lennox-Gastaut syndrome is considered to be relatively low. However, the distinctive features of the seizures suggest that they are highly prevalent: at least 5% of people of all ages suffering from epilepsy, and nearly 10% of patients with epilepsy in infancy and adolescence.

[ 2 ], [ 3 ], [ 4 ], [ 5 ]

Causes Lennox Gusteau syndrome

To date, the exact causes that lead to the appearance of Lennox-Gastaut syndrome in a child have not been established. There are only a number of factors that, as experts suggest, can give impetus to the development of pathology.

The following risk factors are meant:

• a state of hypoxia in the fetus during the period of intrauterine development;
• negative processes in the child's brain associated with premature birth or fetal developmental delays;
• infectious pathologies in the brain (for example, meningoencephalitis, rubella);
• infantile convulsive syndrome, or West syndrome;
• focal cortical dysplasia of the brain;
• Bourneville disease.

If Lennox-Gastaut syndrome appeared at an older age, the causes may be tumor processes in the brain or cerebrovascular disorders. Provoking factors that contribute to the development of the syndrome after 25 years are head injuries, alcohol abuse, drug use, severe vascular pathologies.

[ 6 ]

Pathogenesis

There is still no information indicating probable disturbances of physiological processes that precede the appearance of Lennox-Gastaut syndrome. However, there is information that the state of the frontal lobes is of great importance in the development of the syndrome symptoms. It can be concluded that these brain structures are primarily involved in the formation of the pathology.

At the stage of development of Lennox-Gastaut syndrome, focal discharges and spike-wave complexes are often detected, and the role of subcortical structures in the course of the pathological reaction is clearly manifested.

Significant interictal spike-wave activity is thought to be of great importance in the development of cognitive disorders – these disorders are the ones that predominantly occur alongside seizures. Lennox-Gastaut syndrome is considered to be a variant of epileptogenic encephalopathy – so to speak, an intermediate form of epilepsy and epileptic status.

The relative influence of spike-wave activity may be reflected in the ability of neuronal networks to generate slow oscillations associated with GABA release, a process that interrupts fast activity.

[ 7 ], [ 8 ]

Symptoms Lennox Gusteau syndrome

For Lennox-Gastaut syndrome, the typical symptomatic triad is:

• widespread slow spike waves in EEG;
• psychomotor retardation;
• a large number of generalized seizures.

Most often, the syndrome is detected in childhood – from 2 to 8 years old, mainly in boys.

The first signs may appear unexpectedly, spontaneously, or as a result of obvious damage to the brain.

Lennox-Gastaut syndrome in children begins with sudden falls. In older children, the first symptoms may be behavioral disorders. Over time, attacks occur more frequently, epileptic seizures appear, intelligence decreases, personality disorders are observed, and in some cases, psychosis is diagnosed.

The occurrence of tonic seizures is the most characteristic feature of Lennox-Gastaut syndrome. Such seizures are in most cases short-lived and last only a few seconds.

There are the following types of such attacks:

• axial (contraction of the flexor muscles of the neck and trunk);
• axial-rhizomelic (lifting with adduction of the proximal parts of the arms, muscle tension of the neck, raising the shoulders, opening the mouth, “rolling” the eyes, short-term holding of the breath);
• global (with a sharp fall of the patient from a standing position).

The attacks of the syndrome may be asymmetrical or lateral. In some cases, tonic convulsions are followed by automatisms. The tonic stage in most cases occurs at the stage of falling asleep, but may also occur during the day.

Infants have slow or delayed psychomotor development. Behavioral disorders are observed in 50% of patients:

• hyperactivity;
• emotional lability;
• aggression;
• autism;
• associativity;
• Disrupted sexual activity.

In addition, the development of chronic psychoses with periodic exacerbations is observed.

In approximately 17% of cases, patients have no neurological features.

[ 9 ]

Stages

Lennox-Gastaut syndrome can occur in various stages:

• Atonic stage – characterized by a sharp drop in tone, for 1-2 seconds. Consciousness may be impaired during this time. Since the stage lasts an extremely short time, it may be manifested externally by a sharp weakness in the neck, or a nod of the head.
• Tonic stage – characterized by increased muscle tone (muscles contract sharply, group, “become numb”). The stage lasts from a couple of seconds to several minutes – more often when waking up from sleep.
• The absence stage is a brief "switching off" of consciousness. The patient seems to freeze, fixing his gaze on one point. At the same time, there is no fall.

In infants, seizures can be longer - up to half an hour, or frequent, with extremely short breaks between seizures.

[ 10 ], [ 11 ], [ 12 ]

Forms

Seizures in Lennox-Gastaut syndrome are not always the same and have their own species-specific differences:

• Generalized seizure:

1. convulsive seizure;
2. minor seizure (absence, myoclonus, akinesia);
3. status epilepticus.

• Focal seizure:

1. motor seizure (chewing, tonic, myoclonic convulsions);
2. sensory seizure (impaired vision, hearing, smell, taste, dizziness);
3. mental attack (attack-like psychosis, dysphoria);
4. automatism;
5. speech attack (attack-like loss of articulation);
6. reflex attack.

[ 13 ], [ 14 ], [ 15 ], [ 16 ]

Complications and consequences

The clinical symptoms of such a pathology as Lennox-Gastaut syndrome require long-term and complex drug correction. Over time, the disease can be complicated by severe neurological and social consequences:

• recurrence of seizures, even with treatment;
• resistance to treatment;
• intellectual disability that persists throughout life;
• impaired social and work adaptation.

Tonic seizures that occur against the background of a persistent decrease in intellectual activity are not amenable to treatment.

In addition, other common complications of Lennox-Gastaut syndrome are possible:

• the attack may end with a fall and injury to the patient;
• status epilepticus is a complication characterized by a series of repeated seizures that are accompanied by irreversible changes in the brain;
• The attack can be fatal – and this complication is not uncommon.

[ 17 ], [ 18 ], [ 19 ]

Diagnostics Lennox Gusteau syndrome

The first step in diagnosing Lennox-Gastaut syndrome is collecting anamnesis. The doctor will primarily pay attention to the following questions:

• When did the first seizure occur?
• How often do attacks occur, how long do they last and what are they like?
• Does the patient have other medical conditions? What medications are they taking?
• If the disease is diagnosed in a baby, then it is necessary to clarify how the mother’s pregnancy and labor proceeded.
• Has the patient had any head injuries?
• Have you had any behavioral problems or other odd behavior?

Tests are not a criterion for diagnosing Lennox-Gastaut syndrome, but they often allow the disease to be differentiated from other pathologies:

• blood biochemistry;
• determination of blood glucose levels;
• OAC;
• renal function assessment (RAA);
• liver function tests;
• spinal puncture;
• tests for the presence of infection in the body.

Instrumental diagnostics is the main one and involves the use of the following diagnostic methods:

• Electroencephalography is a procedure that records and measures brain waves.
• Videoelectroencephalography is a procedure similar to the previous one, which allows monitoring the state of the brain in dynamics.
• Computer tomography is a computer scan of brain structures. High resolution allows for a high-quality examination of both bone formations and soft tissues.
• Magnetic resonance imaging is a safe and informative diagnostic method that is most recommended for assessing the condition of the brain in children.

Additionally, the doctor may prescribe positron emission tomography, single-photon emission CT, which are performed only simultaneously with magnetic resonance imaging.

[ 20 ]

Differential diagnosis

Differential diagnostics are performed to exclude other diseases that could cause symptoms similar to Lennox-Gastaut syndrome. Such diseases primarily include:

• Short-term loss of consciousness associated with cerebrovascular accidents. Such moments are usually not accompanied by rhythmic convulsions.
• Migraine attacks accompanied by severe (usually one-sided) headache.
• Panic attacks that can be mistaken for partial seizures. Panic is usually accompanied by tachycardia, increased sweating, tremors, shortness of breath, weakness, phobia.
• Narcolepsy is a neurological disorder in which a person suddenly "switches off" and falls asleep. At the same time, there is a sharp loss of muscle tone.

Treatment Lennox Gusteau syndrome

For the treatment of Lennox-Gastaut syndrome, both medicinal and surgical methods are used.

Drug therapy has a positive effect only in 20% of patients. Surgical treatment involves dissection of the corpus callosum - callosotomy surgery. In addition, it is possible to perform surgeries to stimulate the vagus nerve and resect vascular tumor processes and malformations.

The use of Carbamazepine and Phenytoin helps to control generalized seizures and reduce the frequency of attacks – but these medications can have the opposite effect in some cases. Valproate drugs (derivatives of valproic acid) stop or weaken any type of seizures, but their effect is too short-lived.

A good effect is expected from the use of Felbamate, which allows to reduce the frequency and severity of attacks. But it is noted that the use of this drug is accompanied by a large number of side effects. Based on this, Felbamate is prescribed only in extreme cases, with regular monitoring of liver function and blood condition, for a period of no more than 8 weeks.

Other medications that are often used to treat Lennox-Gastaut syndrome include Nitrazepam and Vigabatrin.

Corticosteroids, with a slow decrease in dosage, can help the patient at the initial stage of the syndrome, during the period of epileptic status and during periods of worsening of the pathology. Additionally, Amatantadine, Imipramine, Tryptophan or Flumazenil are prescribed.

Medicines for the treatment of Lennox-Gastaut syndrome

	Method of administration and dosage	Side effects	Special instructions
Clobazam	Take 20-30 mg per day in two doses, or once at night. The course of treatment is 1 month.	Fatigue, trembling fingers, drowsiness, nausea, loss of appetite.	Longer-term use of the drug should be agreed with a doctor.
Rufinamide	Take twice daily with food, starting with a daily dose of 200 mg, with a possible increase to 1000 mg per day.	Headache, dizziness, drowsiness, vomiting.	The drug is discontinued gradually, with a 25% reduction in dosage every two days.
Convulex	The drug is administered intravenously, at an average daily dose of 20-30 mg per kg of body weight.	Liver dysfunction, headache, ataxia, tinnitus, gastrointestinal disorders.	During treatment, it is necessary to monitor the patient's blood clotting status.
Lamotrigine	The tablets are taken with water, without crushing them, in the amount of 25 mg daily. The dose can be gradually increased to 50 mg per day.	Skin rashes, joint and muscle pain, nausea, diarrhea, deterioration of liver function.	The drug is not used to treat children under 3 years of age.
Topiramate	Take the tablet whole, 25-50 mg per day (in 2 doses). Then individual dosage adjustment is possible in one direction or another.	Anemia, changes in appetite, depression, drowsiness, speech disorders, memory impairment, tremor.	The drug is discontinued gradually to avoid recurrence of seizures.

Use of immunoglobulins in Lennox-Gastaut syndrome

Over the last decade, clinical medicine has begun to actively use large intravenous doses of immunoglobulin. Such preparations are represented by pooled, virus-inactivated, standard polyvalent human immunoglobulin. The basis of the preparation is immunoglobulin IgG, as well as a small percentage of IgM and IgA.

Initially, immunoglobulin was introduced into use to eliminate disturbances of natural immunity in all kinds of conditions of primary or secondary immunodeficiency.

Immunoglobulin preparations are obtained from donor plasma. The mechanism of their action has not yet been fully clarified: experts assume a complex effect on the body.

There are no specific therapeutic regimens that are used to treat Lennox-Gastaut syndrome. Most often, dosages from 400 to 2000 mg per kg of body weight per course are used, with a single dosage of 100-1000 mg per kg for 1-5 injections. The frequency of injections may vary.

Vitamins

Vitamins are essential for the normal course of vital processes in the body of a patient with Lennox-Gastaut syndrome. But taking vitamin preparations should be controlled, otherwise the patient's condition may worsen.

• A disorder of vitamin B ₆ metabolism can cause seizures in children.
• Long-term use of anticonvulsants can reduce the level of some vitamins in the body: tocopherol, vitamin D, ascorbic acid, vitamins B ₁₂, B ₆, B ₂, folic acid, β-carotene.
• Deficiency of the above vitamins in the body of a patient with Lennox-Gastaut syndrome can lead to the development of various cognitive disorders.

Vitamins for the treatment of the syndrome should be taken only under the supervision of a doctor, because unbalanced or chaotic intake of certain vitamin preparations can affect the effectiveness of other medications. In addition, for example, long-term or unjustified intake of folic acid can lead to new seizures.

Physiotherapy treatment

Physiotherapy treatment for Lennox-Gastaut syndrome is used with great caution. Not all procedures are indicated for patients. Very often, even after one or two sessions, patients experience an exacerbation.

Doctors are most loyal to the following physiotherapeutic methods:

• inductothermy (sometimes in combination with galvanic baths);
• hydrotherapy (massage shower, medicinal baths);
• UHF;
• therapeutic mud;
• sollux;
• hyperbaric oxygenation method;
• electrophoresis with iodine and novocaine, calcium chloride, lidase, etc.

With properly selected physiotherapy treatment, the frequency of attacks decreases, they become less pronounced. This effect can last up to six months.

Acupuncture and massage are not recommended for Lennox-Gastaut syndrome.

Folk remedies

In case of Lennox-Gastaut syndrome, it is necessary to follow a special diet, excluding spicy, salty, pickled foods, as well as coffee, chocolate, cocoa, carbonated drinks, alcohol. It is advisable to reduce the amount of liquid consumed, especially at night.

To prevent new attacks, it is useful to eat white onions or drink onion juice. The mechanism of action of onion juice is unknown, but it has been noted that it weakens and reduces the frequency of attacks.

Scientists have proven that daily regular consumption of omega-3 fatty acids, even in small quantities, can reduce the number of attacks in Lennox-Gastaut syndrome. Therefore, it is recommended to drink 1 tbsp. of flaxseed oil or fish oil every morning. In addition, you can cook fatty sea fish (this can be sardines, mackerel, tuna), or take special dietary supplements.

People successfully use Maryin root - it helps not only with Lennox-Gastaut syndrome, but also with neurasthenia, paralysis, epilepsy. Alcohol tincture of the plant petals is prepared at the rate of 3 tbsp. raw materials per 500 ml of vodka, infused for 1 month. The tincture is taken 1 tsp. up to 3 times a day.

[ 21 ], [ 22 ]

Herbal treatment

• It is useful to drink a celandine infusion for Lennox-Gastaut syndrome. To prepare it, take 1 tbsp. of dry raw material and pour 250 ml of boiling water. This drink should be drunk daily, morning and evening, half a glass.
• For prolonged and frequent attacks, an infusion based on caraway seeds will help. You need to pour 1 teaspoon of caraway seeds with one glass of boiling water and leave it in a thermos for 8 hours. Drink the infusion three times a day, 1 tablespoon.
• Three times a day it is necessary to take ready-made peony tincture (can be bought at a pharmacy), in the amount of 40 drops per 100 ml of water, before meals. Peony can be replaced with no less effective motherwort.
• It is useful to take mistletoe tincture internally - 1 tbsp. three times a day, before meals. To prepare the tincture, you need to pour 100 g of raw material with 500 ml of vodka, leave in a dark cupboard for 3 weeks. After this, filter the medicine and use.

Homeopathy

Homeopathic remedies can be used both to prevent attacks and to eliminate an existing attack. It is important to choose the right drug based on the symptoms you have.

• Belladonna is used for sudden convulsions that are accompanied by fever, redness of the face, trembling in the body and limbs.
• Chamomilla is prescribed for convulsions, irritability, night cramps, and angry fits.
• Cuprum metallicum is used to relieve cramps that occur due to shortness of breath or croup.

During an attack, the patient is given one dose of 12C or 30C urgently. If this amount has proven effective, then the intake is stopped. If the attacks continue or recur, then the dose is offered every quarter of an hour until the patient's condition is relieved.

The development of side effects is practically excluded, even when taking increased dosages of drugs.

Among complex homeopathic preparations, specialists give preference to the following remedies:

• Cerebrum compositum is an injection solution intended for intramuscular or subcutaneous administration. The usual treatment lasts up to one and a half months. The medicine is administered 2.2 ml 1-3 times a week.
• Vertigoheel is an injection solution that is administered intramuscularly at 1.1 ml 1-3 times a week for 2-4 weeks.

Surgical treatment

Specialists had high hopes for vagus nerve stimulation – this method of treating Lennox-Gastaut syndrome still requires further development. It was assumed that stimulation and callosotomy surgery would have approximately the same effect. However, a recent study showed that implantation of a stimulator may not be effective in all patients with Lennox-Gastaut syndrome: callosotomy was more effective.

Callosotomy is a surgical procedure that involves cutting the corpus callosum, the main structure that connects both hemispheres of the brain. This operation does not eliminate the disease completely, but it prevents the rapid spread of seizure activity from one hemisphere to the other, which allows the patient to avoid falling during an attack.

The callosotomy operation is not without side effects. Thus, patients who have undergone such an operation may have a mental impairment, which is expressed in difficulties in explanations or the inability to identify body parts. The reason for this is the disrupted connection between the hemispheres.

Another type of surgery, focal cortical resection, is used relatively rarely, only in cases where a separate neoplasm in the form of a tumor or vascular cluster is diagnosed in the brain.

Prevention

There is no specific prevention of Lennox-Gastaut syndrome, since the true causes of the disease have not yet been determined. Moreover, many probable factors that can serve as a trigger in the development of pathology are unpredictable - among them birth injuries, inflammatory processes in the brain.

Patients prone to frequent attacks are advised to follow a dairy-vegetable diet, establish a rational work and rest regimen, and perform regular, measured physical exercises. It is very important not to give in to negative emotions, dress for the weather (not to overcool or overheat), “forget” about the existence of cigarettes and alcoholic beverages, and not to drink coffee or strong tea.

If possible, it is advisable to spend more time in nature and relax - this will reduce the frequency of attacks and make the patient's life better.

[ 23 ]

Forecast

The prognosis is considered unfavorable, but Lennox-Gastaut syndrome does not transform into epilepsy. Symptom relief and preservation of intellectual abilities are observed only in a small number of patients - while tonic seizures continue to bother, but to a lesser extent.

The most unfavorable course of the syndrome is in patients with impaired brain function, with early onset of the disease, with frequent seizures, with recurring epileptic status.

There is currently no complete cure for Lennox-Gastaut syndrome.

[ 24 ]