content:ohtahara_syndrome

Ohtahara syndrome

Shunsuke Ohtahara [1930-2013]

Ohtahara syndrome is a rare electroclinical epilepsy syndrome with onset in the neonatal period. It is also known as early infantile epileptic encephalopathy (EIEE) or early infantile epileptic encephalopathy with burst suppression pattern. It is named after Shunsuke Ohtahara, the Japanese child neurologist who first described the syndrome in 1976 [1].

  • Incidence has been estimated at 1/100 000 births in Japan and 1/50,000 births in the U.K[2]

Majority of Ohtahara syndrome patients have an underlying structural abnormality. The associated structural abnormalities include hemimegalencephaly, porencephaly, dentato-olivary dysplasia[3], agenesis of the corpus callosum, agenesis of the mamillary bodies[4], cortical dysplasia and neuronal migration disorders. Ohtahara syndrome has also been reported to be caused by underlying metabolic conditions including nonketotic hyperglycinemia, cytochrome C oxidase deficiency, pyridoxine dependency, carnitine palmitoyltransferase deficiency, Leigh encephalopathy, biotinidase deficiency and mitochondrial respiratory chain complex I deficiency.

Although structural abnormalities are the most common underlying finding in Ohtahara syndrome, genetic mutations have also been increasingly reported. Mutations known to be associated with Ohtahara syndrome include syntaxin binding protein 1 (STXBP1) gene[5], Aristaless-related homeobox (ARX) gene, solute carrier family 25 (SLC25A22) gene. However these genetic abnormalities are also related to brain structural abnormalities. For e.g ARX gene mutations can result in hypoplastic corpus callosum, cerebral atrophy, abnormal cavum septum pellucidum and abnormal hippocampi and basal ganglia. STXBPI mutations have been associated with brain stem structural abnormalities. The tonic seizures seen in Ohtahara syndrome are thought to be originating in the brain stem[6].

Other genes associated with Ohtahara syndrome include CDKL5; SPTAN1; KCNQ2; ARHGEF9; PCDH19; PNKP; SCN2A; PLCB1; SCN8A; ST3GAL3; TBC1D24; BRAT1

Ohtahara syndrome presents in early infancy, within the first 3 months of age, and often within the first 2 weeks of life[7]. Infants develop tonic spasms that are either generalized or lateralized. The spasms occur either singly or in clusters and are unrelated to the sleep cycle. The spasms can occur several times per day and typically last upto 10 seconds. Some children also develop other seizure types including focal motor seizures, hemiconvulsions, or generalized tonic-clonic seizures.

img|title
Electroencephalogram of a 3-month old girl showing typical suppression burst pattern seen in Ohtahara syndrome. Time base, 30 mm/second; sensitivity, 10 μV/mm. (Adapted from Beal et al.2012[6]

In Ohtahara syndrome electroencephalograms charactaristically show a suppression burst pattern, with bursts of high-amplitude spikes and polyspikes that alternate at a regular rate with periods of electric suppression (see Figure 1). The bursts coincide with the tonic spasms[8]. The pattern typically remains the same during both wakefulness and sleep.

  • Pseudorhythmic repetitive suppression-burst pattern without physiological rhythms
  • Age-related evolution to hypsarrhythmia of West syndrome and then to slow spike-wave patterns of Lennox-Gastaut syndrome.
  • tonic spasms of variable duration concomitant with the burst phase
  • When tonic spasms cluster in intervals of 5 to 10 sec there could be diffuse desynchronization with disappearance of suppression-burst activity or the suppression-burst pattern could become more frequent, diffuse, and of higher amplitude compared to the inter-ictal pattern.

Diagnosis is based on the clinical picture and the electrographic characteristics. Neuroimaging is warranted to look for structural abnormalities.

  • EEG
  • MRI
  • Genetics- CGH Microarray followed by epilepsy gene panel and whole exome sequencing if necessary

Treatment depends on management of the epilepsy.

  • Anti-seizure medications
  • Vagal Nerve Stimulation (VNS)
  • Ketogenic diet
  • Epilepsy surgery
  • Prognosis is universally poor
  • Ohtahara syndrome can evolve to West syndrome and then to Lennox-Gastaut syndrome, or can transition to severe focal epilepsy
  • High incidence of mortality & morbidity with permanent cognitive and neurologic deficits

There is considerable clinical overlap between the two conditions and some authors have suggested that they are part of a spectrum since they have similar pathophysiologic pathways[6].

Aarons Ohtahara E-mail: https://sites.google.com/a/ohtahara.org/ohtahara2/contact-us Website: http://www.ohtahara.org/

Epilepsy Foundation 8301 Professional Place East Suite 230 Landover, MD 20785 Toll-free: 800-332-1000 (24/7 Helpline) Telephone: +1-301-459-3700 Fax: +1-301-577-2684 E-mail: contactus@efa.org Website: https://www.epilepsy.com/ en Español 1-866-748-8008


1. a Ohtahara, S. et al. No To Hattatsu. 1976; 8: 270–280
2. a RESERVED IU–AR. Orphanet: Early infantile epileptic encephalopathy Ohtahara syndrome [Internet]. [cited 2020 Jan 28]. Available from: http://icnapedia.org/s/ohtahara-syndrome
3. a Schlumberger, E.et al. Early-infantile epileptic syndrome(s) with suppression-burst: Nosological considerations. in: J. Roger, M. Bureau, C.H. Dravet, F.E. Dreifuss, A. Perret, P. Wolf (Eds.) Epileptic syndromes in infancy, childhood, and adolescence. John Libbey & Company Ltd., London; 1992: 35–42
4. a Trinka E et al. Epilepsia. 2001 Jul;42(7):950-3. PMID : 11488899

5. a Saitsu Hirotomo et al. Nat Genet. 2008 Jun;40(6):782-8. PMID : 18469812
6. a, b, c Beal Jules C et al. Pediatr Neurol. 2012 Nov;47(5):317-23. PMID : 23044011
7. a Ohtahara S. Brain Dev. 1984;6(6):509-19. PMID : 6534199
8. a Fusco L et al. Brain Dev. 2001 Nov;23(7):708-14. PMID : 11701283
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