Developmental and/or Epileptic Encephalopathy with spike-wave activation in sleep (D/EE-SWAS)

Developmental and/or Epileptic Encephalopathy with spike-wave activation in sleep (D/EE-SWAS),refers to a spectrum of conditions that are characterized by the EEG feature of spike-wave activation in sleep, share similar clinical features and management implications. This syndrome now incorporates several syndromes previously named Landau-Kleffner syndrome, Epileptic Encephalopathy with Continuous Spike-Wave in Sleep and Atypical Benign Partial Epilepsy (pseudo-Lennox syndrome)and it is recommended that these terms no longer be used^[1].

• The EEG pattern previously required for this syndrome was known as continuous spike-wave in sleep (CSWS) and the clinical correlate previously known as electrical status epilepticus in
• sleep (ESES).
• Cognitive, behavioral, and motor regression occur at the same time or within weeks of EEG exhibiting SWAS, characterized by continuous, slow (1.5-2Hz) spike-waves in slow sleep, typically occupying >50% of slow sleep.
• The diagnosis of D/EE-SWAS requires that the child show temporally related cognitive, behavioral or motor regression with the EEG pattern
• EE-SWAS occurs in a child with normal development, whereas D/EE-SWAS occurs in one with preexisting developmental delay or just language delay.
• Children may present with an auditory agnosia where they do not recognize common sounds, such as the doorbell or telephone ringing. They show loss of understanding and have an acquired aphasia.
• Seizures do not occur in all children. When present they may range from easily controlled focal motor seizures to drug-resistant seizures of multiple types
• Specific focal epilepsy syndromes, such as SeLECTs and SeLEAS, or other structural focal epilepsies may evolve to D/EE-SWAS, either transiently or for a prolonged period.

• onset of seizures between 2 and 12 years of age (peak 4-5 years),
• EEG develops spike-wave activation in sleep 1-2 years after seizure onset in association with cognitive or behavioral regression
• thalamic injury in early life, and malformations such as bilateral perisylvian polymicrogyria increases the risk
• Regression in cognitive, behavioral, or psychiatric functioning is the main sign of this condition. This can impact all cognitive areas, including language, communication, temporo-spatial orientation, attention, and social interaction.
• Clinical seizures typically remit around puberty, even in patients with a structural lesion
• Resolution of clinical seizures may precede, coincide with, or follow the resolution of the EEG pattern
• Focal discharges may persist both during wakefulness and sleep

Resolution of SWAS on EEG often leads to neurocognitive and behavioral improvement. Many patients have residual disability, limiting independence in around half of them. Cognitive result is primarily influenced by D/EE-SWAS length and etiology, with higher risk of poor outcome for those with the condition for over 2 years . Younger onset of D/EE-SWAS is associated with worse results.

• Seizure type is dependent on the underlying etiology.
• D/EE-SWAS may occur in patients who do not have clinical seizures
• early seizures are typically focal motor, with or without impaired awareness, and focal to bilateral tonic-clonic seizures
• as cognitive and/or behavior regression sets in , seizures typically worsen with the evolution of multiple seizure types which include focal seizures with or without impaired awareness, typical and atypical absence seizures, atonic seizures and focal motor seizures with negative myoclonus.

• The EEG pattern depends on the underlying etiology.
• The ictal EEG correlates with the seizure type.
• The background activity during wakefulness may show focal or diffuse slowing and often contains focal or multifocal discharges, but it may be normal.
• Epileptiform discharges during wakefulness are not continuous.
• In drowsiness and sleep, there is marked activation of epileptiform activity, with almost continuous, slow (1.5-2Hz) spike-wave in slow sleep, often occupying >50% of slow sleep. Typically, this activity is also seen in Stage II sleep^[1].
• SWAS is usually diffuse but may occur more focally (typically frontally) or multifocally.
• In REM sleep, the discharges become less frequent or may even be absent.
• Normal sleep architecture (vertex sharp waves, sleep spindles and K complexes) is absent or difficult to distinguish.
• An overnight sleep EEG may be required to capture slow wave sleep

• Pathogenic variants in GRIN2A are associated with a range of severity of D/EE-SWAS phenotypes
• These individuals have a characteristic speech pattern which may persist into adult life. Patients with GRIN2A-related speech problems and epilepsy may substitute or omit sounds or syllables. They may speak slowly, use short words, or highlight unwanted areas. They may speak hoarsely or breathlessly. They may speak nasally^[2].
• A family history of seizures is found in up to 50% of D/EE-SWAS individuals.