Practice Essentials Lennox-Gastaut syndrome (LGS), or childhood epileptic encephalopathy, is a pediatric epilepsy syndrome characterized by multiple seizure types; mental retardation or regression; and abnormal findings on electroencephalography (EEG). Signs and symptoms If not present before symptom onset, neurologic and neuropsychologic deficits inevitably appear during the evolution of LGS. Factors associated with more common or more severe mental retardation include the following: An identifiable etiology (ie, symptomatic as opposed to cryptogenic LGS) A history of West syndrome ( infantile spasm) Onset of symptoms before age 12-24 months More frequent seizures Average intelligence quotient (IQ) score is significantly lower in patients with symptomatic LGS than in those with cryptogenic LGS. Earlier age of seizure onset is correlated with higher risk of cognitive impairment. Ictal clinical manifestations include the following: Tonic seizures (frequency, 17-95%) - Can occur during wakefulness or sleep but are more frequent during non–rapid eye movement (REM) sleep; may be axial, axiorhizomelic, or global; may be asymmetric Atypical absence seizures (frequency, 17-100%) – Can have gradual onset, with incomplete loss of consciousness; associated eyelid myoclonias may be noted Atonic, massive myoclonic, and myoclonic-atonic seizures (frequency, 10-56%) – Can all cause a sudden fall, producing injuries, or may be limited to the head falling on the chest; pure atonic seizures are exceptional Other types of seizures (generalized tonic-clonic [15%], complex partial [5%], absence status epilepticus, tonic status epilepticus, nonconvulsive status epilepticus) Findings on general physical examination are normal in many cases. No physical findings are pathognomonic for LGS. Nevertheless, the general physical examination can help identify specific etiologies that have both systemic and neurologic manifestations. No neurologic examination findings are pathognomonic for LGS. However, neurologic examination of an LGS patient may demonstrate the following: Abnormalities in mental status function (specifically, deficits in higher cognitive function consistent with intellectual disability) Abnormalities in level of consciousness, cranial nerve function, motor/sensory/reflex examination, cerebellar testing, or gait (nonspecific findings that are more a reflection of the underlying brain injury or the effect of anticonvulsant medications) Diagnosis No laboratory investigations are known to aid in the diagnosis of LGS. EEG (waking and sleep) is an essential part of the workup. Interictal EEG may demonstrate the following characteristics: A slow background that can be constant or transient Awake – Diffuse slow spike wave Non-REM sleep – Discharges that are more generalized and more frequent, consisting of polyspikes and slow waves REM sleep – Decreased spike waves Ictal EEG may demonstrate the following characteristics: Tonic seizure – Diffuse, rapid, low-amplitude activity pattern that progressively decreases in frequency and increases in amplitude; may be preceded by a brief generalized discharge of slow spike waves or flattening of the recording or followed by diffuse slow waves and slow spike waves; no postictal flattening Atypical absence seizure – Diffuse, slow, and irregular spike waves; occasionally, discharges of rapid rhythms preceded by flattening of the record for 1-2 seconds, followed by progressive development of irregular fast rhythm in anterior and central regions and ending with brief spike waves Atonic, massive myoclonic, or myoclonic-atonic seizure – Slow spike waves, polyspike waves, or rapid diffuse rhythms Absence status epilepticus – Continuous spike wave discharges, usually at a lower frequency than at baseline, and rapid rhythms during tonic status epilepticus Neuroimaging is an important part of the search for an underlying etiology. Modalities include the following: Magnetic resonance imaging (MRI) – Generally preferred Computed tomography (CT) – Preferred in selected situations Routine positron emission tomography (PET) and single-photon emission CT (SPECT) – Lacking current indications for LGS but may be useful in potential candidates for epilepsy surgery Management Medical treatment options may be divided into the following 3 major groups: First-line treatments based on clinical experience or conventional wisdom – Valproic acid, benzodiazepines (specifically, clonazepam, nitrazepam, and clobazam; there have been occasional reports of worsening of tonic seizures by benzodiazepines) Treatments suspected to be effective on the basis of open-label uncontrolled studies – Vigabatrin, zonisamide Treatments proven effective by double-blind placebo-controlled studies – Lamotrigine, topiramate, felbamate, rufinamide Surgical options include the following: Corpus callosotomy – Effective in reducing drop attacks but not typically helpful for other seizure types; considered palliative rather than curative Vagus nerve stimulation – FDA-approved as adjunctive treatment for refractory partial-onset seizures in adults and adolescents older than 12 years Focal cortical resection – May improve seizure control in rare cases The ketogenic diet—involving a high ratio of fats (ketogenic foods) to proteins and carbohydrates (antiketogenic foods)—may be useful in patients with LGS refractory to medical treatment. 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