eMedicine Specialties > Neurology > Pediatric Neurology

Lennox-Gastaut Syndrome

Author: Tracy A Glauser, MD, Professor, Departments of Pediatrics and Neurology, University of Cincinnati College of Medicine, Children's Comprehensive Epilepsy Program, Children's Hospital Medical Center of Cincinnati
Coauthor(s): Diego A Morita, MD, Assistant Professor of Pediatrics and Neurology, Department of Pediatrics, Division of Neurology, Cincinnati Children's Hospital Medical Center, University of Cincinnati; Karen Mary Stannard, MD, FRCPC, Fellow, Pediatric Epilepsy, Cincinnati Childen's Medical Center
Contributor Information and Disclosures

Updated: Jan 5, 2010

Introduction

Background

Childhood epileptic encephalopathy (Lennox-Gastaut syndrome [LGS]) is a devastating pediatric epilepsy syndrome constituting 1-4% of childhood epilepsies.¹ The syndrome is characterized by multiple types of seizures, mental retardation or regression, and abnormal EEG with generalized slow spike-and-wave discharges (1.5-2 Hz). The most common seizure types are tonic-axial, atonic, and absence seizures, but myoclonic, generalized tonic-clonic, and partial seizures can be observed. Seizures often are resistant to therapy.

Pathophysiology

The pathophysiology of LGS is not known. No animal models exist. A variety of possible pathophysiologies have been proposed. One hypothesis states that excessive permeability in the excitatory interhemispheric pathways in the frontal areas is present when the anterior parts of the brain mature. Involvement of immunogenetic mechanisms in triggering or maintaining some cases of LGS is hypothesized. Although one study found a strong association between LGS and the human lymphocyte antigen class I antigen B7, a second study did not. No clear-cut or homogeneous metabolic pattern was noted in 2 separate reports of positron emission tomography (PET) studies in children with LGS.

Frequency

United States

Overall, LGS accounts for 1-4% of patients with childhood epilepsy but 10% of patients with onset of epilepsy when younger than 5 years. The prevalence of LGS in Atlanta, Georgia, was reported as 0.26 per 1000 live births.

International

Epidemiologic studies in the western or industrialized world (Israel, Spain, Estonia, Italy, Finland) demonstrated that the proportion of patients with LGS seems relatively consistent across the populations studied and similar to that in the United States. The prevalence of LGS is 0.1-0.28 per 1000 in Europe. The annual incidence of LGS in childhood is approximately 2 per 100,000 children.²

Among children with intellectual disability, 7% have LGS, while 16.3% of institutionalized patients with intellectual disability have LGS.

Mortality/Morbidity

• Mortality rate is reported at 3% (mean follow-up period of 8.5 y) to 7% (mean follow-up period of 9.7 y). Death often is related to accidents.
• A high rate of injuries is associated with atonic and/or tonic seizures. Some patients with LGS wear protective helmets with face guards to maximize protection of the forehead, nose, and teeth. Unfortunately, some patients with LGS do not tolerate the helmet with face guards, and even if tolerated, helmets often are uncomfortable and rarely are "cosmetically acceptable."
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    Patient with Lennox-Gastaut syndrome wearing a helmet with face guard to protect against facial injury from atonic seizures

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    Patient with Lennox-Gastaut syndrome wearing a helmet with face guard to protect against facial injury from atonic seizures

• The severity of the seizures, frequent injuries, developmental delays, and behavior problems take a large toll on even the strongest parents and family structures. Pay attention to the psychosocial needs of the family (especially siblings). The proper educational setting also is important to help the patient with LGS reach his or her maximal potential.

Race

No racial differences exist in the occurrence of LGS.

Sex

Males are affected more often than females. The relative risk of occurrence of LGS is significantly higher in boys than in girls (prevalence 0.1 per 1000 for boys, 0.02 per 1000 for girls; relative risk 5.31; 95% confidence interval, 1.16-49.35).

Age

The mean age at epilepsy onset is 26-28 months (range, 1 d to 14 y). The peak age at epilepsy onset is older in patients with LGS of an identifiable etiology than in those whose LGS has no identifiable etiology. The difference in age of onset between the group of patients with LGS and a history of West syndrome and those with LGS without West syndrome is not significant. The average age at diagnosis of LGS in Japan was 6 years (range, 2-15 y).

Clinical

History

• Interictal clinical manifestations
  • Although approximately 20-30% of children with LGS are free from neurologic and neuropsychologic deficits prior to onset of symptoms (idiopathic group), these problems inevitably appear during the evolution of LGS. Factors associated with more common or more severe mental retardation are an identifiable etiology (ie, symptomatic) LGS, history of West syndrome, onset of symptoms before age 12-24 months, and more frequent seizures.
  • Average intelligence quotient (IQ) score is significantly lower in patients with symptomatic LGS than in those with cryptogenic LGS, which includes patients for whom no cause of LGS can be identified but a cause is suspected. In one study, IQ testing showed variable degrees of mental retardation in 66% of the cryptogenic group and in 76% of the symptomatic group at first examination. At the last examination, mental retardation was found in 95% of the cryptogenic group and in 100% of the symptomatic group.
  • A significant correlation exists between age of onset of seizures and mental deterioration. In one study, almost 98% of the patients who had an onset of seizures before age 2 years had definite cognitive impairment, compared with 63% of those with onset after age 2 years.
  • Young children with LGS may exhibit mood instability, personality disturbances, or slowing and/or arrest of psychomotor development and educational progress. In contrast, older children with LGS experience character problems, acute psychotic episodes, or chronic forms of psychosis with aggressiveness, irritability, or social isolation. The most impaired of the cognitive functions are reaction time and information processing, which are prolonged. The main characteristics of mental deterioration are reported as apathy, memory disorders, impaired visuomotor speed, and perseverance.
• Ictal clinical manifestations
  • Tonic seizures have a frequency of 17-95%. These seizures can occur during wakefulness or sleep but are more frequent during non–rapid eye movement (REM) sleep. Duration is from a few seconds to a minute. Tonic seizures can be (1) axial tonic, involving the head and trunk with head and neck flexion, contraction of masticatory muscles, and eventual vocalizations; (2) axorhizomelic tonic, in which tonic involvement of the proximal upper limbs with elevation of the shoulders and abduction of the arm occurs; or (3) global tonic, with contraction of the distal part of the extremities, occasionally leading to a sudden fall and at other times mimicking infantile spasms. Tonic seizures can be asymmetric. Some patients may show gestural automatisms after the tonic phase. The tonic seizure may end in a vibratory component if prolonged.
  • Atypical absences range in frequency from 17-100%. This wide range results from parental inability to correctly recognize and identify atypical absences. In one study using video/EEG monitoring in a cohort of children with LGS, parental recognition was 27% for atypical absences, while the sensitivity was as high as 80% for myoclonic seizures and 100% for tonic, atonic, tonic-clonic, clonic, and complex partial seizures. Atypical absences may be difficult to diagnose since their onset may be gradual and loss of consciousness may be incomplete, allowing the patient to continue activities to some degree. Patients may have associated eyelid myoclonias, which are not as rhythmic as in typical absences but often are associated with perioral myoclonias or progressive flexion of the head secondary to a loss of tone. Automatisms may be observed. The seizure end may be gradual in some patients and abrupt in others.
  • Atonic seizures, massive myoclonic seizures, and myoclonic-atonic seizures are noted in patients with LGS with a frequency of 10-56%. These seizures are difficult to differentiate by clinical observation only. Considerable discrepancies exist in the use of these terms. All 3 types can produce a sudden fall, producing injuries (drop attacks, Sturzanfãlle), sometimes limited to the head, resulting in the head falling on the chest (head drop, head nod, nictatio capitis). Pure atonic seizures are exceptional; most have a tonic or myoclonic component.
  • Other types of seizures are noted. Generalized tonic-clonic seizures are reported in 15% of patients, while complex partial seizures occur in 5%. Absence status epilepticus, tonic status epilepticus, and nonconvulsive status epilepticus all can occur, can have a long duration, and can be resistant to therapy.

Physical

• General physical examination
  • Physical examination can be important in helping to identify specific etiologies that may have both systemic and neurologic symptoms (eg, tuberous sclerosis). Often findings on general physical examination are normal in a patient with LGS. No pathognomonic physical findings are present in patients with LGS.
  • Abnormal findings on the general physical examination (eg, adenoma sebaceum, ash leaf macules) may suggest specific etiologies. Use a Wood lamp to examine the skin. Patients may exhibit moderately severe to severe growth delay, a nonspecific finding that is more a reflection of the underlying brain injury than of a specific epilepsy syndrome.
• Neurologic examination
  • Neurologic examination in patients with LGS demonstrates abnormalities in mental status function, specifically deficits in higher cognitive function consistent with intellectual disability.
  • Abnormalities in level of consciousness, cranial nerve function, motor/sensory/reflex examination, cerebellar testing, or gait are nonspecific findings and more a reflection of the underlying brain injury or effect of anticonvulsant medications.
  • No pathognomonic findings are present on neurologic examination in patients with LGS.

Causes

LGS can be classified, according to its suspected etiology, as either idiopathic or symptomatic. Patients may be considered to have idiopathic LGS if normal psychomotor development occurs prior to the onset of symptoms, no underlying disorders or definite presumptive causes are present, and no neurologic or neuroradiologic abnormalities are found. In contrast, patients have symptomatic LGS if an identifiable factor is responsible for the syndrome. Some investigators add cryptogenic as a different etiologic category, in which no identified cause exists but a cause is suspected and the epilepsy is presumed to be symptomatic.

• Idiopathic: Population-based studies found that 22-30% of patients with LGS have idiopathic LGS.
• Symptomatic
  • Population-based studies found that 70-78% of patients with LGS have symptomatic LGS.
  • Examples of underlying pathologies responsible for symptomatic LGS include encephalitis and/or meningitis, tuberous sclerosis, brain malformations (eg, cortical dysplasias), birth injury, hypoxia-ischemia injury, frontal lobe lesions, and trauma.
  • Infantile spasms precede the development of LGS in 9-39% of patients.
• Cryptogenic: In an epidemiologic study in Atlanta, Georgia, 44% of patients with LGS were in the cryptogenic group.
• Family history: In a series of 23 patients with cryptogenic LGS, 2.5-47.8% had a family history of epilepsy and febrile seizures.

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