Lennox-Gastaut syndrome

Definition

Lennox-Gastaut syndrome (LGS) is one of the most severe forms of epilepsy (a seizure disorder) that develops in children usually between one and eight years old. It is characterized by several types of seizures , developmental delay, and behavioral disturbances such as poor social skills and lack of impulse control.

Description

Lennox-Gastaut syndrome can be the result of any one of many neurological problems of childhood that begins with intractable, or hard to control, seizures. French physician Samuel Auguste A. D. Tissot (1728–1797) first described the syndrome in 1770. He reported an 11-year-old boy with frequent drop attacks, myoclonus (jerking movements), and progressive functional impairment. Seizure types vary among children with LGS. The tonic seizures of LGS include stiffening of the body, upward deviation of the eyes, dilation of the pupils, and altered respiratory patterns. Atonic seizures are also experienced by children with LGS and involve a brief loss of muscle tone and consciousness, which causes abrupt falls. Other seizures common in LGS include the atypical absence seizure type (staring spells) and myoclonic seizures (sudden muscle jerks).

Lennox-Gastaut syndrome frequently affects language development in children, ranging from little or no verbal ability to slowness in ideation and expression. Varying degrees of motor difficulties hinder age-appropriate activities such as walking, skipping, or using a writing instrument. Severe behavioral disorders such as hyperactivity, aggressiveness, and autistic tendencies and personality disorders are nearly always present. There is usually mental retardation and sometimes a tendency for psychosis that eventually develops with LGS.

In young children, LGS usually begins with episodes of sudden falls. In the school-age group, behavioral disturbances may be the heralding signs, along with sudden falls. This is soon followed by frequent seizures, episodes of status epilepticus (a continuous seizure state that is associated with a change in the child's level of awareness), progressively deteriorating intellectual functions, and personality disturbances. By age six, most children with LGS have some degree of mental retardation.

When children grow older, the types of seizures often change. In most cases, the drop seizures subside. They are replaced by partial, complex partial, and secondarily generalized convulsions. Among teenagers, complex partial seizures are the most common form.

Demographics

In the United States, Lennox-Gastaut syndrome accounts for 1–4% of older children with epilepsy, but 10% of children with epilepsy beginning in the first five years of life. In Europe, studies demonstrated that the proportion of patients with LGS seems similar to that in the US.

No racial differences exist in the occurrence of LGS; however there are differences in respect to sex and age. Males are affected more often than females; the relative risk of occurrence of LGS is significantly higher in boys than in girls (one in 10,000 boys, and one in 50,000 girls). The average age for the onset of seizures is three years.

Causes and symptoms

Causes

Often no specific cause is identifiable, however, some of the known causes include:

• developmental malformations of the brain
• genetic brain diseases such as tuberous sclerosis , and inherited metabolic brain diseases
• brain injury due to problems associated with pregnancy and birth, including prematurity, asphyxia, and/or low birth weight
• severe brain infections, including encephalitis, meningitis, toxoplasmosis, and rubella

In many instances, LGS follows earlier infantile spasms , which are sudden spasms or body bending, either at the trunk or neck. These episodes usually begin between three and eight months of age, and may develop into the mixed seizure pattern that characterizes LGS at two to three years of age.

Symptoms

The main symptom of LGS is the occurrence of seizures. Several different seizure types occur, and a child may experience some or all of these:

• In drop attacks, the child falls suddenly to the ground. This may be because the legs suddenly fold up (atonic seizure) or stiffen (tonic seizures), or because of a violent jerk (myoclonic seizure) that throws the child to the floor.
• During atypical absences, the child appears to be vacant or to stare blankly. Sometimes these seizures are associated with blindness or nodding of the head. Often, children are able to continue their activity to some extent during the seizure. These episodes are usually very brief, but frequent. Sometimes these seizures occur so frequently that they merge into one another. Such a phenomenon can lead to what is called non-convulsive status epilepticus. During these episodes, children may appear to switch off, but can be partly responsive, drool, be unable to speak or eat properly, and be wobbly on their feet.
• Tonic seizures are often difficult to detect as they occur much more frequently at night. During these attacks, there is general stiffening of the arms or legs. This may be associated with the eyes rolling up or the head moving back. Sometimes, breathing is interrupted and the child may turn blue. If the attacks last for more than 10–20 seconds, the arms often start to tremble rapidly while remaining stiff.

Most children with LGS experience some degree of impaired intellectual functioning or mental retardation. In approximately 65% of children with LGS, intellectual disability is evident, either previous to or at the time of diagnosis. Behavioral disturbances are also usually present, including persistent attention-seeking behavior, impulsiveness, lack of regard for personal safety and fearlessness, and, in severe cases, autistic behaviors. These behavior disturbances may be the result of the condition causing LGS, effects of a particular medication, uncontrolled epilepsy, difficulty interpreting information, or even a lower level of concept understanding.

Diagnosis

LGS is diagnosed by some or all of the following symptoms, including:

• presence of a mixed seizure pattern
• some degree of developmental delay or intellectual disability
• distinct, slow, spike-and-wave pattern shown during electroencephalogram (EEG)

Magnetic resonance imaging (MRI) is an important part of the search for an underlying cause in a child with LGS. Abnormalities revealed by MRI associated with LGS include tuberous sclerosis, brain malformations, or evidence of previous brain injury.

Treatment team

Treatment for LGS involves a multidisciplinary team that may include a neurologist , a neuropsychologist , and a neurosurgeon. A dietitian may help with specialized diet regimens.

Treatment

The drug treatment for LGS is based on the use of anti-epileptic drugs that are effective in reducing the number of seizures. However, the improvement often only lasts for a period of months or, rarely, a year or more. Carbamazepine , sodium valproate, vigabatrin, lamotrigine , and the benzodiazepines (clobazam, in particular) are often prescribed.

One alternative treatment involves a ketogenic diet in which 87% of calories come from fat, 6% from carbohydrates, and 7% from protein. The diet is restrictive, difficult to follow, but has shown results in reducing seizures in some affected children. Other less conventional therapies such as intravenous immunoglobulin therapy have also been attempted.

For children with repeated drop attacks, a procedure to cut the corpus collosum (the large group of nerve fibers connecting the two halves of the brain) may be very helpful. However, this procedure involves significant surgery and is not always effective, and seizures may return after several months or years.

An implanted vagus nerve stimulator is effective in reducing seizures in many children with Lennox-Gastaut syndrome. It is a device, similar in size to a heart pacemaker, that is implanted in the chest with a lead wrapped around the vagus nerve in the neck. It is able to stimulate the vagus nerve automatically at adjustable intervals. The device may take months to show maximum benefit, and requires a surgical procedure for insertion as well as for removal. The batteries require replacement approximately every eight to ten years, which entails further surgery.

Recovery and rehabilitation

A very small percentage of children with LGS experience a spontaneous improvement in seizures, usually during adolescence. In these cases, mental function also shows some improvement. In the overwhelming majority of cases, however, emphasis is placed on maximizing quality of life rather than recovery.

Protective devices such as helmets and pads may be necessary during periods of high seizure activity, but many children and parents consider them too burdensome and restrictive for continuous daily use.

Clinical trials

Although as of early 2004 there were no ongoing clinical trials for LGS, the National Institutes of Health (NIH) sponsors research related to many seizure disorders. Information on the numerous current clinical trials for the study and treatment of seizure disorders can be found at the NIH Web site: <http://clinicaltrials.gov/search/term=Seizure+Disorder>.

Prognosis

The prognosis for individuals with LGS is unfavorable, but variable. Long-term studies of children with LGS found that a majority of patients continue to have typical LGS characteristics (mental retardation, treatment-resistant seizures) many years after onset. Children with an early onset of seizures, prior history of West syndrome, higher frequency of seizures, or constant slow EEG background activity have a worse prognosis than those with seizures beginning later in childhood. Tonic seizures may persist and be more difficult to control over time, while myoclonic and atypical absences become easier to control.

Special concerns

It is recognized that the frequency of seizures may be associated with the child's level of alertness. The child who is overexcited or lacks sufficient stimulation may experience more seizures. Therefore, a stable but stimulating environment may be important in reducing the number of daily seizures. This may include a strict routine of regular meals, sleep, and medication.

Providing for the safety of a child with Lennox-Gastaut syndrome is a 24-hour concern for parents. Coupled with safety concerns, children with LGS are often dependent for personal care such as toileting, management of behavioral impulses, and interpretation of attempts at communication. Often, respite care can provide parents with a chance to reenergize. As the child matures into adulthood, an assisted living center or group home may help provide maximum independence and social integration, along with continued medical supervision.

Resources

BOOKS

The Official Parent's Sourcebook on Lennox-Gastaut Syndrome: A Revised and Updated Directory for the Internet Age. San Diego: Icon Group International, 2002.

PERIODICALS

Frost, M., et al. "Vagus Nerve Stimulation in Children with Refractory Seizures Associated with Lennox-Gastaut Syndrome." Epilepsia 42 (2001): 1148–1152.

OTHER

NINDS Lennox-Gastaut Syndrome Information Page. National Institute of Neurological Disorders and Stroke. March 10, 2004 (May 23, 2004). <http://www.ninds.nih.gov/health_and_medical/disorders/lennoxgastautsyndrome_doc.htm>.

ORGANIZATIONS

Lennox-Gastaut Syndrome Group. 3872 Lyceum Avenue, Los Angeles, CA 90066. (310) 391-0335; Fax: (310) 397-2687. [email protected].

Epilepsy Foundation. 4351 Garden City Drive, Suite 500, Landover, MD 20785-7223. (301) 459-3700 or (800) EFA-1000 (332-1000); Fax: (301) 577-2684. [email protected]. <http://www.epilepsyfoundation.org/>.

NIH/NINDS Brain Resources and Information Network. PO Box 5801, Bethesda, MD 20824. (301) 496-5751 or (800) 352-9424; Fax: (301) 402-2186. <http://www.ninds.nih.gov/>.

Greiciane Gaburro Paneto

Iuri Drumond Louro, MD, PhD