New Screening Tool Addresses Challenges in Identifying Adults Living With Lennox-Gastaut Syndrome (LGS)

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Lennox-Gastaut syndrome (LGS) is a severe and progressive form of epilepsy characterized by recurrent seizures that typically begin in early childhood, usually between 2 to 7 years of age with a peak onset between 3 to 5 years.¹ LGS is rare, accounting for 1-4 percent of all cases of childhood epilepsy.¹ In the United States, approximately 48,000 children and adults have LGS.² There is variability in the type of seizures individuals with LGS experience, although approximately 70 percent experience tonic seizures, which cause the muscles to contract uncontrollably.³

Almost all children with LGS develop learning problems and intellectual disability, with many experiencing delayed development of motor skills such as sitting and crawling.^1,4 Most people with LGS require help with usual activities of daily living.⁵

LGS is typically diagnosed based on the presence of multiple generalized seizure types, a slow-spike-and-wave (SSW) pattern on electroencephalogram (EEG) and cognitive dysfunction.¹ However, LGS can be challenging to diagnose because of the lack of specific biological markers, numerous etiologies, and varied presentation at onset.

If LGS is not diagnosed in childhood, the condition frequently goes undiagnosed in adults due to evolving presentation of the syndrome over time, the lack of prior patient history and challenges in the transfer of pediatric testing results to adult providers. This results in many adults living with LGS not receiving a formal diagnosis, potentially limiting access to more specialized care for their condition. The challenges in diagnosis beyond childhood prompted an effort to further support new approaches to identifying LGS in adults.

REST-LGS Offers Improved Screening for LGS

The Refractory Epilepsy Screening Tool for LGS patients (REST-LGS) was created by a group of experts who care for patients with refractory epilepsy and intellectual and developmental disabilities, who all share a common goal of improving the identification and treatment of patients with LGS.⁶

REST-LGS consists of 8 criteria (4 major, 4 minor) with potential LGS being defined as having 3 major criteria and 2 to 3 minor criteria. The tool previously underwent a preliminary validation which showed high inter-rater reliability amongst epilepsy experts and non-experts in identifying LGS patients in those with uncontrolled epilepsy.

At the 76th American Epilepsy Society (AES) Annual Meeting, data was presented on the real-world application of the REST-LGS tool to evaluate its applicability in adults with drug-resistant epilepsy receiving care in a residential facility. In this study, investigators conducted a retrospective chart review of 100 patients aged 18 and older with drug-resistant epilepsy and Intellectual Development Disorder using REST-LGS to identify adults likely to meet criteria for the disease, but with no formal diagnosis.

Of 74 individuals who did not have a previous LGS diagnosis, REST-LGS identified 42 individuals as having potential LGS. Of the 26 individuals who had a previous LGS diagnosis, 12 were classified as “unlikely LGS.” The majority of these 12 individuals had unavailable data related to the major criteria, including EEG results, age of seizure onset, and history of cognitive impairment. This highlights the challenge of obtaining comprehensive medical history and records in adults who have transitioned into residential care. REST-LGS indicated over half of the individuals without a previous LGS diagnosis should be referred to an epilepsy center for further diagnostic evaluation.⁷

These findings provide an interesting validation of the original tool and demonstrate the potential benefits for both healthcare providers and the community they serve. Given the frequency and variety of seizures in this population, REST-LGS may have broad applicability across multiple settings, including long-term care. Specifically, it can help identify adults living with LGS who have not received a formal diagnosis, as well as exclude those that were previously misdiagnosed, which can have implications for both groups in regard to access to proper care.⁷

As part of Jazz’s commitment to the epilepsy community that extends beyond offering novel treatment options, we believe the use of the REST-LGS tool in clinical practice and group home settings could lead to more timely diagnosis of LGS and could have important implications for treatment options and prognosis, as well as the potential for inclusion on managed care formulary coverage and access to services in the U.S.^8,9

About Lennox-Gastaut Syndrome

Lennox-Gastaut syndrome (LGS) begins in childhood. It is characterized by multiple types of seizures. People with LGS begin having frequent seizures in early childhood, usually between ages 3 and 5. Nearly three-quarters of affected individuals have tonic seizures, which cause the muscles to contract uncontrollably. Almost all children with LGS develop learning problems and intellectual disability. Many also have delayed development of motor skills such as sitting and crawling. Most people with LGS require help with usual activities of daily living.

About Jazz Pharmaceuticals plc
Jazz Pharmaceuticals plc (NASDAQ: JAZZ) is a global biopharmaceutical company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing life-changing medicines for people with serious diseases—often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines and novel product candidates, from early- to late-stage development, in neuroscience and oncology. Within these therapeutic areas, we are identifying new options for patients by actively exploring small molecules and biologics, and through innovative delivery technologies and cannabinoid science. Jazz is headquartered in Dublin, Ireland and has employees around the globe, serving patients in nearly 75 countries. Please visit www.jazzpharmaceuticals.com for more information.

References

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¹ National Organization for Rare Diseases. Rare Disease Database: Lennox-Gastaut syndrome. Available at: https://rarediseases.org/rare-diseases/lennox-gastaut-syndrome/#:~:text=Lennox%2DGastaut%20syndrome%20is%20estimated,be%202%20per%20100%2C000%20children. Accessed October 27, 2022.

² LGS Foundation. How Many People Have LGS? 2022. Accessed November 3, 2022. Available at: https://www.lgsfoundation.org/about-lgs-2/how-many-people-have-lgs/

³ Gastaut H, Roger J, Soulayrol R, et al. Childhood epileptic encephalopathy with diffuse slow spike-waves (otherwise known as “Petit Mal Variant”) or Lennox syndrome. Epilepsia. 1966;7:139-79.

⁴ Arzimanoglou A, French J, Blume WT, et al. Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. The Lancet Neurology. 2009;8(1):82-93.

⁵ Reaven NL, Funk SE, Montouris GD, Saurer TB, Story TJ. Burden of illness in patients with possible Lennox-Gastaut syndrome: A retrospective claims-based study. Epilepsy Behav. 2018;88:66-73.

⁶ Piña-Garza JE, et al. The refractory epilepsy screening tool for Lennox-Gastaut syndrome (REST-LGS). Epilepsy Behav. 2019;90:148-153.

⁷ Wolf, S. et al. REST LGS TOOL: Real World Use to Screen for LGS and Improve Access to Care. American Epilepsy Society 2022 Annual Meeting. Nashville, TN, United States. https://cms.aesnet.org/abstractslisting/rest-lgs-tool---real-world-use-to-screen-for-lgs-and-improve-access-to-care. Accessed November 27, 2022.

⁸ Arzimanoglou A, et al. All children who experience epileptic falls do not necessarily have Lennox–Gastaut syndrome… but many do. Epileptic Disord. 2011;13:S3-13.

⁹ Camfield P, et al. Long-term prognosis for symptomatic (secondarily) generalized epilepsies: a population-based study. Epilepsia. 2007;48:1128-1132.