Lennox-Gastaut syndrome (LGS) is a rare but severe form of childhood epilepsy that was first described by Dr. Henri Gastaut in Marseille, France in 1966.. Dr. William G. Lennox from Boston, United States, described the electroencephalogram (EEG) features of this condition. The syndrome is aptly named after these two neurologists. LGS is characterized by a triad of multiple seizure types, characteristic EEG findings, and intellectual impairment. It is one of the epileptic encephalopathies.
Lennox-Gastaut syndrome (LGS) can occur for many reasons; however, approximately 25% cases have no identified cause. Etiology can be divided into two subtypes:
Secondary or Symptomatic LGS: An underlying pathology can be identified with this subtype and is usually from diffuse cerebral injury. Secondary LGS constitutes approximately 75% of cases. Causes include tuberous sclerosis, infections/inflammation such as encephalitis, meningitis, injuries to the frontal lobes of the brain, birth injury/trauma, metabolic causes, and developmental brain malformations. West syndrome, or infantile spasms, is not a specific cause of LGS, but about 30% of children who develop LGS have a prior history of West syndrome and usually have a more severe clinical course.. Secondary LGS tends to have a worse prognosis.
Lennox-Gastaut syndrome (LGS) accounts for approximately 2-5% of all childhood epilepsies, but it is responsible for roughly 10% of epilepsy cases occurring before the age of five years. The incidence of LGS is estimated at 0.1 to 0.28 per 100,000 population. In children, the incidence is estimated at 2 per 100,000.. Overall prevalence is about 26 per 100,000 people. LGS is more common in males than in females. There are no reports about racial differences. As diffuse brain injury is responsible for a majority of cases, children with developmental and/or intellectual problems are more frequently diagnosed with LGS.
As mentioned, Lennox-Gastaut syndrome (LGS) is characterized by a triad of multiple seizure types, characteristic electroencephalogram (EEG) findings, and intellectual impairment.
Intellectual Impairment: The initial growth in a child with LGS is unremarkable. Decline is seen only after the seizures start and is in the form of developmental delay, intellectual impairment, diminished learning abilities, and behavioral problems. This decline is observed in a majority of the patients and gets worsens with age. Memory and cognition can still be normal in up to 20% of patients, but these patients will lag in processing information. Patients with LGS show psychomotor regression which means a loss of previously acquired skills. Behavior problems include irritability, hyperactivity, and psychosis. Sometimes, it is difficult to differentiate seizures from behavioral issues. Most patients will have mental retardation and static encephalopathy, eventually.
Lennox-Gastaut syndrome (LGS) is diagnosed based on appropriate clinical history (seizure types and intellectual impairment) in the presence of characteristic electroencephalogram (EEG) criteria. A standard evaluation with comprehensive birth (prenatal, perinatal, postnatal) history, history of presenting illness/seizures since the onset, history of associated complaints like psychomotor regression, and a full systemic and neurological examination is necessary. Laboratory investigations include hematology and chemistry panel, urinalysis, urine drug screen, serum ammonia, lactic acid, serum amino acids, acylcarnitine profile, and urine organic acids. Imaging studies include an MRI of the brain with and without contrast with seizure protocol. An EEG with awake and sleep recording (with activating procedures such as photic stimulation and hyperventilation if possible) is essential. A video EEG may be done to capture and characterize the different seizure types.
Characteristic EEG Pattern: The background activity usually shows generalized slowing with bursts of spike and wave discharges (1.5 to 2.5 Hertz) and paroxysms of fast activity (10 to 20 Hertz). The spike and wave activity has the highest amplitude over the frontal region, can be periodic or continuous, and can be focal or generalized. Sleep EEG is very important as there are some electrographic features that are activated during sleep and/or seen exclusively during sleep. The spike and wave epileptiform discharges are more frequent and generalized during the non-rapid eye movement (non-REM) EEG as compared to the REM EEG. Tonic seizures are difficult to diagnose, especially in sleep. It is difficult to different the EEG pattern of tonic seizures from infantile spasm.
Diagnosis of idiopathic/cryptogenic LGS can be a challenge initially as the EEG might not be classic, seizures and clinical symptoms evolve over time, and there is no biological marker for the disease. Regular follow up and repeat EEGs are needed to arrive at the final diagnosis.
Treatment of Lennox-Gastaut syndrome (LGS) revolves around seizure control and includes medical, dietary, and surgical management. Seizure control is associated with improvement in cognition, mood, alertness, and overall quality of life.
Medical Management: The goal of treatment in LGS is seizure control. Medications help, but only to a certain extent. Seizures are usually refractory, are of different types, and need multiple medications. Control of tonic and atonic seizures is usually given priority because of associated falls and accidents. Complications arise frequently because when one medication controls one type of seizures, it can cause or worsen another already existent seizure type; for example, carbamazepine might worsen drop attacks. Thus, knowing seizure types becomes important. Multiple medications have been approved for LGS including felbamate, lamotrigine, rufinamide, valproate, benzodiazepines, topiramate, and recently, cannabidiol oral solution.  Valproate, lamotrigine, and topiramate are considered first-line medications for LGS. A summary of the medications is as follows:
Dietary management: Seizures in LGS are often refractory to medical management. The next step is dietary modifications. These modifications have been studied in children and adults and can decrease seizures and perhaps reduce medication doses. Diets that have been tested include Ketogenic diet, modified Atkins diet, and low-glycemic index treatment.
Surgical management: It is the next step in the management of LGS. Surgical management is considered when the first two seizure medications fail. This could be in the form of vagus nerve stimulation (VNS) or brain surgery.
Since there is an evolution of symptoms with Lennox-Gastaut syndrome (LGS), it is difficult to arrive at a diagnosis right away and requires many years of follow-up. Differential diagnoses include Dravet syndrome, myoclonic-atonic epilepsy (Doose syndrome), atypical benign focal epilepsy of childhood, Pseudo-Lennox-syndrome, and West syndrome.
Overall, the outcome remains poor for patients with Lennox-Gastaut syndrome (LGS). The mortality rate is between 3% and 7% in 8 to 10 years of follow-up. Frequently, death can be from accidents. . If there is a history of infantile spasms or West syndrome, the outcome is usually worse with seizure control as well as cognitive status while idiopathic LGS patients have less severe symptoms and resultant impairment. SUDEP or Sudden Unexpected Death is Epilepsy may be more common among LGS patients as they generally have uncontrolled seizures.
The frequent seizures, resultant intellectual impairment, and complex treatment regimen for a patient (child or adult) with Lennox-Gastaut syndrome (LGS) require substantial effort by the parents and family. The majority of the time, LGS patients will require 24/7 support in some form. A coordinated approach is needed from a team including a pediatrician, neurologist, psychiatrist, neuropsychologist, and surgeon. Most patients and families will benefit from assessment and help from social and rehabilitation services (physical, occupational, and speech therapy). Efforts need to be made so that patients with LGS receive early intervention whether it be regarding diagnosis, treatment, education, or support services. Families need to be given information about the LGS Foundation and the Epilepsy Foundation of America.
Every year, November 1 is observed as International Lennox-Gastaut Syndrome (LGS) Awareness Day.
Lennox-Gastaut syndrome (LGS) is a rare but severe form of childhood epilepsy characterized by a triad of multiple seizure types, characteristic EEG findings, and intellectual impairment. It is one of the epileptic encephalopathies. The frequent seizures, resultant intellectual impairment, and complex treatment regimen for a patient (child or adult) with Lennox-Gastaut syndrome (LGS) require substantial effort by the parents and family. The majority of the time, LGS patients will require 24/7 support in some form. A coordinated approach is needed from a team including a pediatrician, neurologist, psychiatrist, neuropsychologist, and surgeon. Most patients and families will benefit from assessment and help from social and rehabilitation services (physical, occupational, and speech therapy). Efforts need to be made so that patients with LGS receive early intervention whether it be regarding diagnosis, treatment, education, or support services. Families need to be given information about the LGS Foundation and the Epilepsy Foundation of America.
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