Acute encephalopathy with biphasic seizures and late reduced diffusion

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), also known as acute encephalopathy with biphasic seizures and late restricted diffusion, is a rare, acute, often parainfectious, pediatric encephalopathy syndrome.

Epidemiology

Acute encephalopathy with biphasic seizures and late reduced diffusion is considered rare, although the exact global incidence and prevalence is not known. The condition manifests in infants, and is more common in East Asian populations ¹. In Japan, where the condition is particularly common, approximately 100 cases are reported per year ¹.

Clinical presentation

Acute encephalopathy with biphasic seizures and late reduced diffusion has a typical biphasic clinical course ^1-8:

• first phase

  • initial prolonged (>30 mins) convulsive febrile seizure

  • this is followed by a fluctuating but usually reduced conscious state, with or without persisting fever

  • during this phase, the electroencephalogram is encephalopathic

• second phase

  • occurs day 4-6 into illness

  • recurrence of seizures, with clusters of focal seizures with or without impaired awareness

  • during this phase, the electroencephalogram may show periodic patterns and/or interictal epileptiform discharges

Following this biphasic course, there is a gradual recovery over weeks to months ³.

Pathology

The pathogenesis of acute encephalopathy with biphasic seizures and late reduced diffusion is yet to be fully elucidated. It is thought that there is an infective, often a viral, trigger in half of cases, and that this trigger results in neuronal injury secondary to excitotoxicity ^2,3. Multiple potential viral triggers have been identified, including HHV-6, HHV-7, influenza, echovirus, dengue and COVID-19 ^2,5,6,7.

Radiographic features

MRI

Acute encephalopathy with biphasic seizures and late reduced diffusion has distinct radiographic features appreciable on MRI brain, particularly on DWI, that vary during its biphasic clinical course ^1-8.

• first phase

  • T2/FLAIR: normal

  • DWI: normal

  • MR spectroscopy: increased glutamine-glutamate peak, low NAA peak

• second phase

  • T2/FLAIR: may show linear hyperintensities affecting the subcortical U-fibers

  • DWI: bright tree appearance, which can be unilateral or bilateral, often sparing perirolandic regions

  • MR spectroscopy: normal glutamine-glutamate peak, low NAA peak persists

Treatment and prognosis

Mainstay of management is supportive care with antiseizure medications and hypothermia management ^1-3,6,7. However, other treatments have been utilized, including immunosuppressive or anti-inflammatory therapies (e.g. corticosteroids, intravenous immunoglobulin, plasma exchange, tocilizumab) and neural protective therapy (e.g. 'mitochondrial cocktails' of vitamins) ^1-3,6,7.

Prognosis is variable ^1-3. Approximately 60% of all patients will have persisting neurological morbidity (e.g. focal neurological deficits, epilepsy, cognitive deficits), however, the mortality rate is low (5%) ^1-3.

History and etymology

Acute encephalopathy with biphasic seizures and late reduced diffusion was first described in 2006 ⁴.

Differential diagnosis

Clinical differential diagnoses with distinctly different radiographic features:

• febrile infection-related epilepsy syndrome (FIRES)

• acute necrotizing encephalopathy

Differential diagnoses with similar clinicoradiographic features:

• acute leukoencephalopathy with restricted diffusion (ALERD)

• hemorrhagic shock and encephalopathy syndrome (HSES)

• hemiconvulsion-hemiplegia epilepsy syndrome (HHE)

• traumatic brain injury with a biphasic clinical course and late reduced diffusion (TBIRD)