Early Myoclonic Encephalopathy (Neonatal Myoclonic Encephalopathy)

Early Myoclonic Encephalopathy (Neonatal Myoclonic Encephalopathy)

Aleksandra Djukic

Federico Vigevano

Perrine Plouin

Solomon L. Moshé


In 1978, Aicardi and Goutieres described a group of five patients with “neonatal myoclonic encephalopathy” commencing in the hours immediately after birth and consisting of erratic, asynchronous, nonperiodic myoclonus associated with generalized jerks and a distinctive electroencephalogram (EEG).3 Since then, the syndrome has been referred to as early myoclonic encephalopathy and also as myoclonic encephalopathy with neonatal onset,8 neonatal epileptic encephalopathy with periodic EEG bursts, and early myoclonic epileptic encephalopathy9 and neonatal myoclonic encephalopathy.3,39

In 1989, the ILAE Commission of Classification and Terminology recognized the syndrome as “early myoclonic encephal- opathy (EME)” and classified it as generalized symptomatic epilepsies of nonspecific etiology.16 In 2001 the entity was finally recognized as one of the “epileptic encephalopathies” together with early infantile epileptic encephalopathy with suppression-bursts (EIEE, Ohtahara syndrome), West syndrome, and Lennox-Gastaut syndrome. Since 1978, there have been published reports on 50 patients with the characteristic clinical picture—onset of symptoms during the first month of life consisting of erratic, fragmentary myoclonus, massive myoclonus, partial seizures, suppression-burst EEG pattern, and, later, tonic spasms; the prognosis is grave.4 Some controversial issues on differential diagnosis from EIEE and physiopathology remain; there are several cases of early encephalopathy with seizures and a suppression-burst pattern that do not fulfill the criteria for either EIEE or EME.4,10,18,33


The syndrome is rare. An epidemiologic study of childhood epilepsy in Japan detected 4 cases of EME (0.168%) among 2,378 children with epilepsy >10 years of age.6,28 In a study of 75 infants with epilepsy of neonatal onset, Watanabe et al.42 observed 2 cases (2.7%) of EME. A gender difference, with female-to-male ratio of 1:1.3, is seen in the 30 cases published in the English literature.10


In most cases, the etiology of EME is unknown. Although EME is assumed to be associated with inborn errors of metabolism, even the most frequently reported diagnosis—nonketotic hyperglycinemia—is rarely documented.2,5,9,13,27,33,38,39 Other identified inborn errors of metabolism are D-glyceric acidemia, propionic acidemia, molybdenum cofactor deficiency, methylmalonic acidemia, mitochondrial dysfunction, and abnormal urinary oligosaccharides.

Structural brain malformations (cerebellar hypoplasia, migrational disorder with cortical dysgenesis) have also been reported.11,23

Wang and colleagues reported a patient with a clinical picture of early myoclonic encephalopathy and an atypical suppression-burst pattern, with full recovery after administration of pyridoxine.40 The syndromes of retinal pigmentary degeneration and nephronophthisis, congenital nephrotic syndrome, and Zellweger disease have all also presented with EME.2,5,9,13,15,19,21,23,27,33,39,40

Familial occurrence has been reported,2,9,33,40 reflecting the genetic nature of the underlying diseases. Because the gene locations for these metabolic errors vary widely, however, it is more likely that EME does not develop due to a specific genetic abnormality but rather due to extensive cortico-subcortical dysfunction as a consequence of a severe metabolic disorder.27

Clinical Presentation

Seizure Characteristics

In this condition, a child usually born without dysmorphic features and after an uneventful delivery undergoes a regression as the seizures emerge and becomes less alert and irritable and with poor interactions.9 The distinctive clinical characteristic of EME is myoclonias, which are the first presenting symptom, starting usually within the first week of life. The majority of the patients present within the first month of life. Onset during the prenatal period and during the second or third month of life has been reported but is rare.9,11,40

Myoclonus is fragmentary and erratic and shifts from one to another body part in a random, asynchronous fashion; it can become massive and generalized in some cases.4 Initially, it involves eyelids, face, and limbs in the form of twitches of small to moderate amplitude. Sometimes, twitches are restricted to a very small territory (eyebrow, corner of the mouth). The frequency of myoclonic jerks also varies from occasional to almost continuous from the onset. It may persist during sleep.9

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Aug 1, 2016 | Posted by in NEUROLOGY | Comments Off on Early Myoclonic Encephalopathy (Neonatal Myoclonic Encephalopathy)
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