Lennox-Gastaut syndrome (LGS) is a catastrophic epilepsy also known as an epileptic encephalopathy—with onset occurring in early childhood, typically before 8 years of age, most commonly between 3 and 5 years old.

Because LGS can be caused by a myriad of underlying conditions (including unknown causes, which may be connected to genetic factors), it can be difficult to diagnose and treat.

LGS Foundation. Lennox-Gastaut Syndrome. Epilepsy.com.

 

 

 

 

Diagnosis criteria for LGS 

 

LGS is a rare and severe form of epilepsy that predominantly affects the pediatric population. Its epidemiology reflects its rarity, with an estimated incidence of 0.1 to 0.3 cases per 100,000 individuals. 

While there is a slight male predominance in LGS cases, the underlying reasons for this gender difference remain to be elucidated.

The International League Against Epilepsy has created criteria for diagnosing LGS.

Specchio N, Wirrell EC, Scheffer IE, et al. ILAE Classification and Definition of Epilepsy Syndromes with Onset in Childhood: Position Paper. ILAE Task Force on Nosology and Definitions.

These include the presence of multiple and mixed seizure types, such as tonic, atonic, generalized tonic-clonic, myoclonic, and atypical absence seizures. 

 

The characteristic EEG findings in LGS play a pivotal role in its diagnosis and characterization. Notably, LGS is associated with a distinctive EEG pattern characterized by slow spike-wave activity, typically in the 1.5 to 2.5 Hz range, often observed during non-REM sleep. 

Additionally, high-amplitude generalized paroxysmal fast activity is frequently seen, particularly during waking and light sleep states, often accompanied by slow waves. The presence of generalized slow background activity further contributes to the typical EEG features of LGS.

Cognitive impairment is a prominent and almost universal feature in LGS, ranging from mild to severe intellectual disability, significantly impacting daily functioning. Patients may exhibit behavioral issues, including impulsivity, aggression, and mood disorders. 

Physical comorbidities, such as mobility impairment due to falls during seizures and a heightened risk of sudden unexpected death in epilepsy, further compound the complexity of managing LGS.

According to Lourdes Bello, MD, pediatric epileptologist at Stony Brook Comprehensive Level 4 Epilepsy Center in Stony Brook, NY, the multiple types of seizures caused by LGS “are usually resistant to treatment, with many patients requiring multiple anticonvulsant medications.” More so, HCPs must address both the seizures themselves in addition to the comorbidities associated with the syndrome.

 

Differentiating LGS from other conditions

 

While LGS has distinct clinical and electrographic features, it can sometimes mimic or be mistaken for other neurological or developmental disorders due to overlapping symptoms and diagnostic challenges.

Age

Firstly, considering the age of onset is crucial. LGS typically emerges in early childhood, with most cases appearing before the age of 8. In contrast, Doose syndrome usually starts between 1 and 5 years of age, whereas Dravet syndrome typically presents during the first year of life—often within the first few months. This distinction in the timing of onset can provide a significant diagnostic clue.

Seizure type

Secondly, the spectrum of seizure types should be thoroughly examined. LGS is known for its diverse array of seizure types (including the aforementioned tonic, atonic, generalized tonic-clonic, myoclonic, and atypical absence seizures). Doose syndrome, however, predominantly features myoclonic and atonic seizures, with fewer variations in seizure types compared with LGS. Meanwhile, Dravet syndrome is characterized by prolonged febrile seizures followed by various types of seizures, including myoclonic, atypical absence, and generalized tonic-clonic seizures, often triggered by fever.

EEG results

EEG findings can also offer critical insights. In contrast to LGS’s slow spike-wave activity and generalized paroxysmal fast activity, Doose syndrome often displays a characteristic generalized fast polyspike-wave pattern. Differentiating LGS from Dravet syndrome on EEG involves considering background activity, interictal spikes, and seizure patterns. 

 

Medication response

Lastly, evaluating the response to medications is essential. LGS is notoriously resistant to antiepileptic drugs, often requiring a combination of therapies. Doose syndrome may respond better to certain medications, including valproate and stiripentol, which can lead to improved seizure control. In contrast, Dravet syndrome typically shows poor response to many antiepileptic drugs.

 

 

Missed or incorrect diagnoses

 

Adults may have LGS as well, but “it is very uncommon that patients reach adulthood without being diagnosed with this condition,” Dr. Bello tells MDLinx. 

According to Epilepsy & Behavior Case Reports, people diagnosed with LGS as adults are generally diagnosed based on current and past symptoms (such as treatment-resistant seizures, cognitive and motor impairment, and an abnormal EEG).

Piña-Garza JE, Chung S, Montouris GD, et al. Challenges in identifying Lennox–Gastaut syndrome in adults: A case series illustrating its changing nature. Epilepsy Behav Case Rep. 2016;5:38-43.

That said, it’s likely that an earlier LGS diagnosis was simply missed or lost over time. 

 

Research shows that for adult patients with LGS, a poor outcome is common—regardless of age at seizure onset or etiology. As adults, they experience hard-to-manage seizures, intellectual disability, behavioral issues, and other comorbidities.

Vignoli A, Oggioni G, De Maria G, et al. Lennox-Gastaut syndrome in adulthood: Long-term clinical follow-up of 38 patients and analysis of their recorded seizures. Epilepsy Behav. 2017;77:73-78.

 

 

It is considered that LGS has a long-term outcome that is worse when compared to most of the other type epilepsies, and complete seizure control is not achievable.

“Most patients remain with severe cognitive dysfunction that has a severe impact on social functioning,” Dr. Bello says. 

According to an article published in Epilepsy & Behavior, treatment of LGS in adult patients should incorporate both anti-seizure medication therapy and nonpharmacologic approaches, including diet and even cannabidiol.

Montouris G, Aboumatar S, Burdette D, et al. Expert opinion: Proposed diagnostic and treatment algorithms for Lennox-Gastaut syndrome in adult patients. Epilepsy Behav. 2020;110:107146.

 

 

As patients with LGS progress in age, the syndrome itself can undergo transformations. Dr. Bello highlights this to MDLinx: "The clinical characteristics of LGS evolve as patients grow older, primarily due to brain maturation and alterations in the frequency and nature of seizures, [and] these evolving clinical features may resemble those seen in other forms of epilepsy,” she elaborates.