Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Lennox-Gastaut Syndrome

What is Lennox-Gastaut Syndrome (LGS)?

• The Lennox-Gastaut syndrome (LGS) is a type of epilepsy with multiple different types of seizures, particularly tonic (stiffening) and atonic (drop) seizures. Intellectual development is usually, but not always, impaired.​
• Lennox-Gastaut Syndrome (LGS) accounts for only 2 to 5% of childhood epilepsies.
• Seizures are hard to control and patients will need life-long treatment. The intellectual and behavioral problems add to the complexity of this syndrome and the difficulties in managing life with LGS.​
• LGS constitutes between 1-4% of pediatric epilepsies and typically appears between the second and sixth year of life. This translates to a prevalence of 14,500 – 18,500 children under the age of 18 in the United States and more than 30,000 children and adults in the U.S. ​
• Lennox-Gastaut Syndrome (LGS) is a type of epilepsy that usually develops before the age of 7.   ​
• It occurs more often in boys than girls. ​

How Do You Get It?

• The cause of the disorder is unknown in 1 out of 4 of those affected by the disease.​
• Some of the known causes of Lennox-Gastaut Syndrome include brain injury associated with pregnancy or birth (including asphyxia, low birth weight, and prematurity), severe brain infections (including encephalitis, meningitis and rubella), developmental malformations of the brain, or metabolic conditions. ​
  • The diagnosis of LGS does not exclude other developmental or neuropsychiatric diagnoses. 
• LGS can be caused by genetic disorders such as tuberous sclerosis
• An estimated 20% of children with LGS have a prior history of infantile spasms (often referred to as West syndrome).​

What Are The Symptoms?

• The syndrome is characterized by a triad of signs including multiple seizure types, moderate to severe cognitive impairment, and an abnormal EEG with slow spike-wave complexes.​
• Children
• Many children are typically developing normal when first diagnosed, but then begin to lose skills, sometimes dramatically, in association with uncontrolled seizures
• Young children with LGS may exhibit behavioral issues, personality disturbances, mood instability, and slowing of psychomotor development.
  • Behavioral disturbances can include poor social skills and attention seeking behavior, which can be caused by the effects of the medication, difficulty interpreting information, or due to continued electrical disturbances in the brain.​
• Some children with LGS are prone to develop non-convulsive status epilepticus (a continuous seizure state that is associated with a change in the child’s level of awareness). This requires medical intervention to bring it to an end. ​
  • As children with Lennox-Gastaut Syndrome grow older, types of seizures may change. In most cases, the drop-seizures (atonic) are replaced by partial, complex partial, and secondarily generalized convulsions.
  • The uncontrolled seizures may become less of an issue as children grow, but impaired intellectual functioning and behavioral problems persist
• Older children with LGS experience acute psychotic episodes, forms of psychosis with aggressiveness, character problems, and irritability.​
• Cognitive problems include slowed reaction time and information processing. The main characteristics of mental deterioration are reported as apathy, memory disorders, impaired visuomotor speed, and perseverance
• Adults
• As the patient reaches their 20s, only 30-50% maintain the characteristic EEG (slow spike-wave pattern) and clinical characteristics.​
• In 33% of patients with cryptogenic LGS (no underlying cause) and 55% with symptomatic LGS (known cause), the characteristic LGS features disappeared with age.
  • Seizure types often change or decrease in frequency, while behavior disturbances may persist or change with age.
  • Tonic seizures are the most common seizure type in adulthood but may become less common during the day and occur most often during sleep. ​
• Since daytime tonic and atonic seizures may decrease or disappear over the years, adult LGS subjects may not retain the same tendency to fall as compared to youth.​ Other seizure types may change, decrease, or evolve into more complex partial and generalized tonic clonic seizures. Some patients later develop focal temporal lobe epilepsy. ​
• A more favorable outcome is more likely to occur in patients with a later age LGS onset, probably because the brain has already progressed beyond certain critical developmental stages and seizures have a less detrimental impact on intellectual development.​
• Types of Seizures Associated with LGS
  • Tonic seizures are also known as drop attacks because they can cause the patient who is standing to be thrown to the ground. Doctors don’t usually diagnose LGS unless the child is having tonic seizures. ​
    • Generally, muscles tighten (this can happen to a specific set of muscles, or most muscle groups at once), the eyes roll back, and pupils dilate. Tonic seizures can cause faster heartbeats and a temporary stop in breathing. They occur most often during sleep and usually last 10 to 60 seconds.​
  • Atonic seizures are also considered drop attacks. Atonic seizures cause head nods, loss of posture, and sagging at the knees. They are usually very brief, lasting between 1 and 4 seconds.​
  • Atypical absence​ is the second most common seizure associated with LGS. Atypical absences are characterized by a gradual onset and termination1 as well as staring, pauses in activity, and a lack of response. They are generally 5 to 30 seconds long​
  • Clonic: A period of jerking movements
  • Myoclonic: seizures consist of sporadic jerks. They usually happen in the same way on both sides of the body.​
  • Partial: During partial seizures, a specific part of the brain does not work properly. Certain movements, emotions, sensations, and feelings can be affected.​
  • Tonic-clonic: In the first phase of tonic-clonic seizures, the stiffening associated with tonic seizures occurs. It then gradually changes to the clonic phase, in which the muscles quickly switch between contraction and relaxation.​

How Is It Treated?

• The goal of treatments for patients is the best quality of life with the fewest seizures, the fewest adverse treatment effects, and the least number of medications. ​
• Although there is no cure for Lennox-Gastaut Syndrome, there are numerous treatment options available.​
• Health Care team may include PCP, neurologist, neurosurgeon, therapist, dietician, and neuropsychologist. 
• Medications​
• Carbamazepine
  • Atretol​
  • Carbagen SR​
  • Epitol​
  • Mazepine​
  • Tegretol​
  • Tegrital​
  • Teril​
  • Timonil​
• Carbamazepine-XR
  • Carbatrol​
  • Tegretol XR​
• Clobazam
  • Frisium​
  • Onfi*
• Clonazepam
  • Epitril​
  • Klonopin​
  • Rivotril​
• Diazepam
  • Diastat​​
  • Valium​
• Divalproex Sodium​
  • Depacon​
  • Depakote​
  • Epival​
• Divalproex Sodium-ER
  • Depakote-ER
• Eslicarbazepine Acetate​
• Ethosuximide
• Ezogabine​
• Felbamate
• Gabapentin
• Lacosamide
• Lamotrigine
• Levetiracetam
• Levetiracetam XR
• Lorazepam
• Oxcarbazepine
  • Oxtellar​
  • Oxtellar XR​
  • Trileptal​
• Perampanel​
• Phenobarbital
• Phenytoin
  • Dilantin​
  • Epanutin​
  • Phenytek
• Pregabalin
• Primidone
• Rufinamide
  • Banzel*​
  • Inovelon
• Tiagabine Hydrochloride
• Topiramate
• Topiramate XR
  • Qudexy XR*​
  • Trokendi XR*​
• Valproic Acid​
  • Convulex​
  • Depakene​
  • Depakote​
  • Orfiril​
  • Valporal​
  • Valprosid​
• Vigabatrin​
• Zonisamide
• IVIG (intravenous immunoglobulin) is a blood product administered intravenously which may be used in the treatment of Lennox-Gastaut Syndrome and other forms of refractory epilepsy. IVIG comes from human plasma (the portion of the blood where the immune globulins and other blood proteins are contained (1) and is formed by taking antibodies from thousands of blood donors.
• Corticosteroids (predominantly prednisolone and hydrocortisone) and adrenocorticotropic hormone (ACTH) have been used in the treatment of the epilepsies for over 50 years.
  • ACTH continues to be used as the first line treatment choice for Infantile Spasms (IS). It is generally accepted that oral corticosteroids or ACTH will reduce or stop IS and normalise EEG findings in between 50% and 75% of patients within a week or two of starting treatment. However, controversy exists regarding the relation between the duration of spasms prior to diagnosis and response to treatment in terms of both the short and long term (specifically developmental and cognitive) outcome.​
• Cannabidiol (CBD) is a compound found in cannabis that has therapeutic use for individuals living with Lennox Gastaut Syndrome. The compound is said to quiet chemical and electrical activity in the brain without the drawback of effects from cannabis that THC typically includes. 
• The Ketogenic Diet is used to treat children with refractory (resistant to treatment) epilepsy including Lennox-Gastaut Syndrome who have not responded well to anti-epileptic medicines. 
  •  A high fat, low carbohydrate diet that forces the body to burn more fat than sugar. The diet is restrictive containing a 4:1 ratio by weight of fat to protein and carbohydrates, but has been shown to be an effective medical therapy for intractable childhood epilepsy.
  •  Puts the body into a state of ketosis, which is said to have an anti-convulsant effect. When carbohydrates are restricted, the liver converts fat into fatty acids and ketone bodies. The ketones replace glucose as the energy source in the brain and sends the body into ketosis.​
  •  Starts with the strict supervision of a doctor and dietitian, followed by a 24 hour fasting period to raise the ketone level in the brain. The diet is then gradually introduced into the child’s body.​
    
  • Over one half of those children who are placed on the diet have a 50% reduction of seizures or more. The diet requires strict supervision and even the slightest departure may cause the diet to lose its effect.​
    
• Surgery may be recommended to those patients who do not respond to the usual seizure medications or other therapies available. The most common surgical procedures for patients with Lennox-Gastaut Syndrome include the corpus callosotomy and the Vagus Nerve Stimulator. Some literature has argued that resective surgery may also be an options for patients with Lennox-Gastaut Syndrome.​

Where Can I Learn More???

• Check out our cornerstone on this disease here.