What are the diagnostic criteria for Lennox-Gastaut syndrome?

Diagnostic Criteria for Lennox-Gastaut Syndrome

Lennox-Gastaut syndrome (LGS) is diagnosed based on a triad of features: multiple seizure types (which must include tonic seizures), characteristic EEG abnormalities, and cognitive impairment. 1, 2, 3

Core Diagnostic Criteria

1. Multiple Seizure Types

• Mandatory: Tonic seizures (especially nocturnal)
• Common additional seizure types:
  • Atonic seizures (drop attacks)
  • Atypical absence seizures
  • Myoclonic seizures (less frequent)

2. EEG Abnormalities

• Interictal: High voltage, bifrontal 1.5-2.5 Hz slow spike-and-wave complexes
• Ictal: Attenuation with paroxysmal fast activity (10-13 Hz)
• Background slowing is common

3. Cognitive/Developmental Impairment

• Most patients develop moderate intellectual disability within years of onset
• Behavioral problems (inattention, hyperactivity, aggression)

Additional Diagnostic Features

Age of Onset

• Classical onset before 8 years of age (typically between 1-8 years)
• Some cases with later onset have been described

Drug Resistance

• Poor responsiveness to antiseizure medications
• Refractory seizures are characteristic

Diagnostic Challenges and Pitfalls

1. Timing of Tonic Seizures: Tonic seizures may not be present at onset but develop later in the course of the disease. This can lead to delayed diagnosis 1

2. Differential Diagnosis: Early in the course, LGS may be difficult to distinguish from:

   • Dravet syndrome (severe myoclonic epilepsy of infancy)
   • Doose syndrome (myoclonic-astatic epilepsy)

3. EEG Findings: While characteristic, the EEG features are not pathognomonic and must be interpreted in clinical context 1

4. Diagnostic Accuracy: Recent research applying ILAE diagnostic criteria found that up to 52% of patients historically diagnosed with LGS may not meet strict criteria, particularly those with longer duration of epilepsy 3

Etiology Assessment

Most cases are symptomatic (secondary to an underlying brain disorder):

• Prenatal/perinatal insults
• Intrauterine infections
• Brain malformations (migrational abnormalities)
• Genetic disorders (e.g., tuberous sclerosis)
• Inherited metabolic disorders

A minority of cases are cryptogenic (no identifiable cause) 1, 4

Diagnostic Workup

1. Detailed seizure history: Document all seizure types with particular attention to tonic seizures
2. EEG monitoring: Ideally video-EEG to capture both interictal and ictal patterns
3. Neuroimaging: MRI to identify structural abnormalities
4. Genetic testing: Consider when appropriate, especially in cryptogenic cases
5. Metabolic screening: In selected cases without clear etiology

Prognostic Implications

Early and accurate diagnosis is critical as LGS is associated with:

• Poor long-term seizure control
• Cognitive decline
• High mortality rates (standardized mortality ratio >4.5) 3
• Frequent seizure-related injuries (>25% of patients) 3

The application of strict diagnostic criteria is essential for appropriate treatment selection, accurate prognostication, and inclusion in clinical trials for novel therapies 2, 3.