Lennox-Gastaut syndrome is a separate form of childhood epilepsy characterized by the presence of polymorphic paroxysms (myoclonic, atonic, tonic and absences) and delayed neuro-mental development. It may have a cryptogenic character or act as a syndrome of other pathological conditions (cerebral anomalies, genetic metabolic diseases, perinatal pathology). Lennox-Gastaut syndrome is diagnosed by the typical variable pattern of epiprimes and the characteristic pattern of the electroencephalogram. Additionally, MRI and CT scans of the brain are performed. Anticonvulsant therapy of the syndrome is ineffective, alternative treatment methods are being sought. The prognosis is variable, but in most cases unfavorable.
General information
Lennox-Gastaut syndrome (LGS) is a variant of childhood epilepsy characterized by a combination of atonic, myoclonic, tonic seizures and atypical absences, a slow island wave pattern of the EEG. In 1950, LGS was isolated as a separate epileptic syndrome, and in 1964-1966, the neurological community recognized it as an independent nosological form. According to various data, Lennox-Gastaut syndrome accounts for from 3% to 10% of all cases of childhood epilepsy. Its prevalence ranges from 1-2.8 cases per 10 thousand. It is somewhat more common in boys. The typical age of onset of the disease is from 2 to 5 years, less often — 6-8 years. Today, LGS is a serious disease with a progressive course, the effective treatment of which is still the subject of hopes of many specialists in the field of pediatric neurology and epileptology.
Causes
Lennox-Gastaut syndrome refers to diseases whose etiological factors have not yet been precisely established. It is known that in many cases the syndrome is symptomatic and is formed against the background of genetic pathology, the consequences of various adverse factors acting in the perinatal period and in the 1st year of life. However, in most cases, the morphological substrate of the disease remains undetected. The etiofactors capable of provoking the development of LGS include fetal hypoxia, intrauterine infections (rubella, cytomegaly, herpes, toxoplasmosis), birth injuries of newborns (primarily intracranial), prematurity, asphyxia of newborns, severe infectious diseases of the postnatal period (meningitis, encephalitis), brain development abnormalities (hydrocephalus, cortical dysplasia, hypoplasia of the corpus callosum, etc.), metabolic disorders with central nervous system damage, certain genetic diseases (for example, tuberous sclerosis).
In 25-40% of cases, Lennox-Gastaut syndrome occurs in children with a family history of epilepsy. In addition, there is a hypothesis about the etiological role of immune disorders, including those arising from vaccination. In about 30% of cases, LGS is a consequence of the evolution of West’s syndrome. When Lennox-Gastaut syndrome manifests against the background of complete well-being in the child’s health and the absence of the above factors in his anamnesis, they speak of a cryptogenic (having no probable cause) form of the disease. The cryptogenic variant of LGS occurs in 10-20% of cases and is characterized by a more favorable course.
Symptoms
The symptomatic Lennox-Gastaut syndrome, as a rule, debuts against the background of an already existing lag in mental and mental development. In the cryptogenic form, the development of the child at the time of manifestation of the syndrome corresponds to the norm. LGS is characterized by a large variability of seizures, their different duration and frequency.
Atonic paroxysms are caused by a short-term loss of muscle tone. With their generalized nature, a child falls, the so-called “drop attack”. Local paroxysms can take the form of sudden bending of the knees, falling of objects from the hands, nodding of the head, etc. A distinctive feature of atonic episodes in LGS is their lightning speed and short duration (up to 5 seconds). Generalized atonic paroxysms of LGS require differentiation from attacks of myoclonic-astatic epilepsy, fainting, and MSCs.
Myoclonic paroxysms are local muscle twitches. More often they cover the flexor muscles of the proximal parts of the arms, when spreading to the lower extremities, a fall occurs. They are characterized by symmetrical serial occurrence in both limbs and stereotyping. They need differentiation with myoclonia in tick-borne encephalitis and toxic lesions of the central nervous system; myoclonus of a non-epileptic nature, for which irregular asymmetric myoclonias are typical, arising in response to various sensory stimuli (sound, light, touch) and not accompanied by EEG changes.
Tonic paroxysms of LGS often occur during sleep and are characterized by their short duration (average duration of 10 seconds). They are accompanied by a blackout. They may have a generalized character or manifest themselves in the form of tonic tension of individual muscle groups (posterior, dorsal, abdominal muscles, shoulder girdle, etc.). Tonic paroxysms are accompanied by tachycardia, cyanosis of the face, lacrimation, apnea, hypersalivation. Minimal local paroxysms of a tonic nature can sometimes hardly be differentiated from yawning or stretching.
Atypical absences are associated with a partial violation of consciousness. They are manifested by temporary “stupor”, the absence of any motor activity. With a short duration, absences are often not recognized by people around the child. With LGS, absences may be accompanied by muscular hypotension (atonic absences) and hypertonicity of the back muscles (retropulsive absences). More often than other types of epilepsy, Lennox-Gastaut syndrome is accompanied by the status of absences — continuously following each other absences. Such a non-convulsive epistatus usually occurs upon awakening, can last for several hours and days.
Delayed psychomotor development (DPD) is noted in almost all cases of LGS. Its severity depends on the form of the syndrome (cryptogenic or symptomatic), the nature of the background pathology of the central nervous system, the severity and frequency of epileptic paroxysms. As a rule, problems with learning new skills and assimilation of new information come to the fore. Aggressiveness, hyperactivity, emotional instability, characteristic features of autism are often observed. About 50% of adolescents with Lennox-Gastaut syndrome do not have self-service skills. Another 25% are socially and emotionally maladapted due to severe oligophrenia. The peculiarities of behavior and character do not make it possible to adapt normally in society, even for those patients whose oligophrenia has a mild degree of severity. Normal social adaptation is observed only in 15% of cases.
Diagnostics
Lennox-Gastaut syndrome is established on the basis of a typical clinical picture consisting of polymorphic epiprimes and symptoms of delayed neuro-mental development. The age of onset of paroxysms and family history of epilepsy are also taken into account. Electroencephalography plays an important diagnostic role. Intercrime (interictal) The EEG in the waking state registers poor structuring and slowness of the main rhythm. The EEG pattern has a picture of hypsarrhythmia with a large number of spikes of various amplitudes. The highest peaks are recorded in the frontal region. The EEG pattern during seizures depends on their form.
Neuroimaging methods (MRI and CT of the brain) reveal mainly nonspecific pathological changes: internal hydrocephalus, atrophy of subcortical areas and cortical structures mainly of the frontal zone, hypoplasia of the frontal lobes. Attempts to analyze the degree of utilization of glucose by cerebral tissues with the help of PET of the brain gave contradictory information: in some cases, areas of hypermetabolism were identified, in others — hypometabolism; in some patients, glucose metabolism was within normal limits.
Due to the large variability of paroxysms, Lennox-Gastaut syndrome should be differentiated from a number of other forms of epilepsy that make their debut in childhood: myoclonic epilepsy, benign rolandic epilepsy, West syndrome, childhood absentee epilepsy, dysmetabolic epilepsy in Gaucher, Crabbe, Niemann-Pick disease, etc.
Treatment
Therapy is carried out with antiepileptic drugs. Valproic acid, ethosuximide, carbamazepine, lamotrigine, etc. are used. In most cases, combined treatment is carried out with one of these pharmaceuticals and sodium valproate. However, up to 90% of cases of Lennox-Gastaut syndrome are resistant to anticonvulsant therapy. In this regard, the main goal of treatment is to reduce the number of epiprimes and improve the quality of life of the child and his family in the interparoxysmal period.
Neurologists and epileptologists are searching for new ways of therapy. The positive role of the ketogenic diet, consisting in a sharp restriction of the use of carbohydrates and an increase in the fat content in food, has been proven. A number of clinicians have noted the positive effect of treating Lennox-Gastaut syndrome with large doses of immunoglobulin. The effectiveness of the use of ACTH and glucocorticoids was observed. In cases where Lennox-Gastaut syndrome is accompanied by frequent and severe epiparoxysms with a fall and the threat of traumatization of the child, together with a neurosurgeon, the issue of surgical dissection of the corpus callosum — callosotomy may be considered. Such an intervention does not relieve patients from seizures, but significantly reduces their intensity.
New methods of treatment include implantation of a vagus nerve stimulator and an RNS stimulator. In the first case, the device is installed subcutaneously in the clavicle area, and its electrode is passed to the vagus nerve passing in the neck. According to studies conducted in the USA and Europe, in 60% of cases, this device allows you to reduce the number of epiprimes. In the second case, the device is sewn under the scalp, and its electrodes are implanted in the area of the epileptogenic focus. With their help, like an EEG, the device constantly registers the electrical activity of the brain. When receiving signals indicating an incipient paroxysm, the device generates response pulses that provide suppression of epileptic activity.
Forecast
Lennox-Gastaut syndrome has a mostly unfavorable prognosis. Up to 10% of cases result in the death of children during the first decade of life. Deaths are mainly associated with severe traumatization during epiprimes with a fall. Prognostically unfavorable criteria are considered: manifestation of the syndrome at an earlier age, the onset of seizures against the background of ZPR, previous West syndrome, high frequency and intensity of paroxysms. The impossibility of drug relief of epiprimes leads to progressive ZPR. Almost all patients have marked mental retardation to varying degrees, half of the patients are not capable of self-care.