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Internal Medicine

Early infantile epileptic encephalopathy (EIEE)

Introduction

Ohtahara syndrome (OS), also known as early infantile epileptic encephalopathy (EIEE) is a progressive epileptic encephalopathy characterized by frequent tonic spasms, with/without clustering, of early onset within a few months of life, and a suppression-burst (S-B) pattern in electroencephalography (EEG).

  • Earliest known age of onset for any age-dependant epileptic syndrome (often presenting within days of birth or even prenatally)

Early infantile epileptic encephalopathies:

Epilepsies in which the ictal and interictal epileptiform (clinical and EEG) abnormalities may contribute to progressive cerebral dysfunction.
  • Ohtahara syndrome (OS) or early infantile encephalopathy (EIEE)
  • Early Myoclonic Encephalopathy (EME)
  • West Syndrome (WS) (70% EIEE cases progress to WS)
  • Lennox–Gastaut syndrome (LGS) (59% WS cases develop into LGS)
  • Myoclonic status in nonprogressive encephalopathies
  • Dravet syndrome or Severe myoclonic infantile epilepsy (SMEI)
  • Landau-Kleffner syndrome
  • Electrical status epilepticus during sleep
  • CDKL5 Encephalopathy

History:

In 1976, Dr Shunsuke Ohtahara described an epilepsy syndrome affecting very young infants with characteristic electroencephalographic changes, and termed it “early infantile epileptic encephalopathy with suppression-burst”. Ohtahara further observed that this condition frequently evolved into West syndrome (WS) and Lennox-Gastaut syndrome (LGS). The eponym Ohtahara syndrome, which is synonymous with early infantile epileptic encephalopathy, came into prominent use in the mid-1980s.

Professor Shunsuke Ohtahara is well known in the academic world for the disease that he first described and which was named after him: Ohtahara syndrome. This epileptic syndrome is the earliest type of age-dependent epileptic encephalopathy proposed by him, that is consisting of Ohtahara syndrome, West syndrome and Lennox-Gastaut syndrome. Dr. Ohtahara investigated the developmental changes seen in electrophysiological examinations such as EEGs and evoked potentials in many normal children. He found that these electrophysiological parameters showed specific age-related changes that were not necessarily linear but occurred in critical stages. Based on these findings, he happened upon the idea that developmental aspects of childhood epilepsy such as age-dependent epileptic encephalopathy were closely related with these developmental changes in brain functions.

What came to be known as early myoclonic encephalopathy (EME) was first described 2 years after Ohtahara syndrome, in 1978, in neonates with erratic myoclonus and other seizure types. Numerous terms have been applied to this condition, including myoclonic epilepsy with neonatal-onset, neonatal epileptic encephalopathy with periodic electroencephalogram bursts, and early myoclonic epileptic encephalopathy.

In 2001, the Task Force on Classification and Terminology of the International League Against Epilepsy included both “Ohtahara syndrome” and “early myoclonic encephalopathy” within the category of epileptic encephalopathies.

More recently, the proposed organization by the Classification Commission of the International League Against Epilepsy termed both Ohtahara syndrome and early myoclonic encephalopathy as “electroclinical syndromes,” characterized by their clinical and electroencephalographic characteristics.

Aetiology

Structural brain abnormalities:

  • Hemimegaencephaly
  • Absence of corpus callosum
  • Dysplasia

Other causes:

  • Non-ketogenic hyperglycemia
  • Genetic mutations: ARX, STXBP1

Clinical features

Extremely debilitating progressive neurological disorder, involving intractable seizures and severe intellectual disabilities.

Uncontrolled seizure despite anticonvulsants:

Within first 3 months of life
  • Main seizure types: tonic- clonic, myoclonic and atonic and partial spasms
  • Occurence: > 100 brief seizures/day (last for < 10-20 seconds)

Diagnosis

Electroencephalogram (EEG):

  • Characteristic suppression-burst (SB) pattern during both the sleeping and awake states
  • Frequent tonic spasms

Management

  • Anticonvulsants not effective
  • Vigabatrin (DOC)
  • Topamax, Zonegran
  • Corticosteroids
  • ACTH and Ketogenic diet
  • Vagal stimulation

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