Disease of the Month – Lennox-Gastaut syndrome (LGS)

Shots:

Lennox-Gastaut syndrome (LGS) is a severe childhood-onset epileptic condition characterized by repeated seizures

Our Disease of the Month report covers epidemiology, market size, current management strategies, emerging therapeutic options, and patient advocacy groups involved in enhancing patient care. Additionally, we are highlighting the key industry players advancing treatments for LGS

For a detailed epilepsy landscape, analysis and tailored insights contact our experts at connect@pharmashots.com

LGS is a severe form of epilepsy that begins in childhood (age 2-5) and persists till adulthood. It is characterized by seizures, cognitive impairments, and behavioral problems. Between 10-30% of affected children have shown a history of earlier epilepsy syndromes, like West or Ohtahara syndrome. LGS makes upto 3-4% of childhood epilepsy cases. ^[1]

Lennox-Gastaut syndrome (LGS) is accompanied by several types of seizures. These include: ^[1]

Tonic Seizures (stiffening of the body, upward eye gaze, dilated pupils, and altered breathing patterns)

Atypical Absences (staring spells)

Atonic Seizures (brief loss of muscle tone, which could cause abrupt falls)

Myoclonic Seizures (sudden muscle jerks)

Generalized Tonic-Clonic Seizures (muscle stiffness and rhythmic jerking)

LGS can be caused by various conditions, including:

Brain Malformations

Tuberous Sclerosis

Perinatal Asphyxia

Severe Head Injury

Central Nervous System Infection

Inherited genetic and inherited degenerative or metabolic conditions

Symptoms in LGS patients are variable. While some symptoms can be identified in everyday activities, while others only appear during seizures ^[2]

Other Symptoms of LGS according to epilepsy vary by seizure type and may include:^[3]

Temporary loss of consciousness

Uncontrolled muscle movements (e.g., jerking, loss of tone)

Blank stares or difficulty speaking and understanding

Sensory changes (e.g., vision, taste)

Psychic symptoms (e.g., fear, anxiety, déjà vu)

Autonomic changes (e.g., increased heart rate, upset stomach)

You’ll need several tests to confirm an LGS diagnosis, including: ^[2]

Electroencephalogram (EEG): Measures unusual brain activity

MRI: An MRI uses radio waves and a magnetic field to create detailed images of the brain and spinal cord

Lab Testing: Analyzes blood and urine to identify potential causes of seizure activity

Genetic Testing: Detects hereditary conditions or spontaneous mutations that may cause LGS

LGS treatment focuses on seizure control through medical, dietary, and surgical approaches, improving cognition, mood, alertness, and quality of life: ^[4]

Medication: There are many FDA-approved medications for treating LGS: Felbamate, Lamotrigine, Valproate, Rufinamide, Clobazam, Topiramate, and Cannabidiol (CBD) oral solution etc.

Diet Therapy: High-fat, low-carb diets (e.g., ketogenic) are recommended for drug-resistant LGS in children and adults

Surgical management: Surgery is recommended if both medications and diet therapy fail. Surgical management involves:

Vagus Nerve Stimulation: VNS, combined with therapy, is effective for drop attacks and tonic-clonic seizures, with results improving over time, and can also improve mood and behavior

Brain surgery: Surgical options include resection, corpus callosotomy, and hemispherectomy

Incidence: 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 ^[4]

Prevalence: The overall prevalence is about 26 per 100,000 population ^[4]

Gender distribution: LGS is more common in males than in females ^[4]

Age of onset: Most diagnosed between 2 and 5 years old ^[4]

Childhood epilepsy percentage: Accounts for 1-10% of childhood epilepsy cases.^[5]

The global LGS treatment market, valued at $700M in 2022, is projected to reach $1003.12M by 2030, growing at a CAGR of 4.6% from 2023 to 2030 ^[6]

Epidiolex (cannabidiol) is indicated for the treatment of Lennox-Gastaut syndrome (LGS)^[7]

Approved therapies include Fintepla (UCB), Qudexy XR (Upsher Smith), Banzel (Eisai), Sympazan (Assertio Holdings), Felbatol (Viatris), And Epidiolex (Jazz Pharmaceuticals).

Active & Inactive Trials of P-III are concentrated in the US, followed by Spain, Australia, and Italy. Data were extracted on Mar 06, 2025^[8]

Several patient advocacy groups are dedicated to supporting individuals with LGS and improving their quality of life.

Amanda

My daughter Amanda started having seizures when she was two years old.

After many hospitalizations and failing 12 medications, she was diagnosed with LGS, and our quest to find a treatment that worked for her began.

Amanda’s seizures always came in clusters and our family traveled out of state to seek treatment, this affected our family because of the prolonged hospital stays.

Amanda missed 3 years of school because of her seizures and had a lot of struggles over the years with learning simple tasks and concentration.

What has helped Amanda is having a VNS implant for the past 6 years. Currently, she is two years seizure-free and improving every day in her education.

My advice to other parents with loved ones with LGS is to keep doing research and attend as many conferences as possible about LGS and ask questions because it took a long time for us to get a diagnosis for our daughter. My hope is that one day we find better treatments for our children. ^[9]

Valerie

Valerie is smart and sassy. Loving and thoughtful. She gives the best hugs (on her terms only…lol). Valerie never gives up. She loves music, movies, coloring, reading, art, theater and shopping. She has the prettiest brown doe eyes ever.

Valerie is my 4th child and was born on September 11, 2001 (yes, you read that correctly) in Michigan. She was in distress immediately after delivery. Valerie was stabilized and sent home after 24 hours only to be readmitted 2 weeks later.

I knew something was wrong. She was turning blue in her sleep. The doctors found nothing and sent her home. I say nothing, but she had a brain bleed that they were not concerned about.

Then came a move to Texas and hope for better medical services. The first few years were rough. At one year old she had not met most milestones. Enter the first doctor to listen. Valerie was diagnosed with PDD and home services began.

By 3 years old, we noticed what we would later discover to be absence seizures. Another move, this time to Georgia.

By 5 years old, she was in special classes and had her first of many GTC seizures.

Around the age of 10 her already delayed cognitive learning had almost stopped as if frozen in time. At the same time, atonic seizures started (we wouldn’t know they were seizures for about 2 more years).

At age 12 we moved and found a new medical team. A big shout out to CHKD in Virginia. This began a new adventure in the world of epilepsy. We were introduced to many new meds and the amazing VNS. Also, by now Val was having GTC, atonic, focal and myoclonic seizures (about 100+/day).

In 2016, Valerie was formally diagnosed with LGS (after thousands of seizures and so many tests), and we were told her life expectancy was 20. I was devastated. In early 2018, we were introduced to a new medication. By now Valerie was having more than 300 seizures/day. We were desperate for help. We decided after many discussions to try it. It cut her seizures in half. We adjusted her VNS, another 50 or so seizures controlled. Excitement! Back down to about 100 seizures/day.

We moved again in late 2018. Hello, UNC Chapel Hill. The seizures started doing what they do best. They began to push through the meds. Can we please get a break?

For the next 2 years we faced a VNS replacement, multiple emergency room visits, and tried and failed at least 5 more meds.

In 2020 we agreed to an SEEG (29 holes drilled into my daughter’s head). It was horrible, but we needed it for this new implant that we were told was going to be wonderful. Bring on the DBS.

Initially we were not impressed, it wasn’t helping. We continued with emergency room visits and failing more meds.

We had our biggest scare ever October 30, 2022. There was medication shortage… Val ran out. She went into status and was life flighted to Chapel Hill. I was told to say goodbye. NOPE! She remained in the ICU until her meds were made available.

Over the last 2 years there have been more drug trials and failures, VNS and DBS replacements, and of course emergency room visits. We currently have a good med cocktail and 2 working implants, all of them are maxed out.

Valerie still has 60 to 100 seizures daily. Every doctors visit we hear that Valerie is his most difficult to treat patient. We continue with her team of doctors here in North Carolina and at the Mayo Clinic. We are working with genetics and will continue to try new meds. I remain hopeful. I have allowed all of my daughter’s medical info to be used for continued

research. If anything can help to prevent any newly diagnosed children form suffering, then I feel our journey has had a positive impact.

We are actively involved in Special Olympics, our local library and any adventures we can find. Connecting with other LGS parents has been a tremendous blessing. My advice: network with the LGS community, follow your instinct (you know your child best), advocate for your warrior always, do something for YOU every now and then (I hike, camp, and read). Love every minute with your kiddo. I continue to truly cherish the time I have to love my daughter, Valerie. Thank you for reading about our journey^[10]

References