Ohtahara Syndrome

What is Ohtahara Syndrome?

Ohtahara Syndrome (OS) is an epileptic disorder affects infants. This syndrome is rare and often diagnosed within three months age of neonates. The early seizure attack usually occurs at last trimester, (when the fetus in mother’s womb) or within 10 days after the birth of the child.

Both the gender (boy and girl) equally has the chance of Ohtahara Syndrome development. Cognitive functioning impairment and motor malfunctioning are characteristic features of this syndrome and the condition of the neonates become worse as the Ohtahara syndrome is a progressive disorder.

Alternatively, Ohtahara Syndrome (OS) is also known as infantile epileptic encephalopathy or early infantile epileptic encephalopathy^1,2,3.

Clinical Presentation

• Ohtahara Syndrome is not related with ancestors medical history. In most of the cases, the size of the head of the infant is normal, but in some neonates may have an abnormally smaller size of the head (microcephaly).
• The primary anomaly associated with Ohtahara Syndrome is severe impairment of underlying neurological structures.
• Neurology related abnormality may see prior to seizure attacks.
• The Severe developmental delay is associated with Ohtahara Syndrome with or without degenerative conditions.
• Advancement of the Ohtahara Syndrome may cause West or Lennox-Gastaut syndrome development in some affected children^12,3.

Types of Seizure

Different types of Seizures may associate with Ohtahara Syndrome, which includes tonic seizures, partial or focal seizures, atonic and myoclonic or generalized tonic-clonic seizures. Some infants with Ohtahara Syndrome may also suffer from infantile spasms.

In tonic seizures attacks, infants develop stiffness in the upper and lower limbs. The duration of this stiffness lasts for few seconds, but incidence rate is frequent. The tonic seizures attacks may appear as single or in multiple attacks.

Partial or focal seizures usually associated with 1 out of 3 Ohtahara Syndrome affected infants. The origin of the Partial or focal seizures is in brain¹

Causes

The exact cause of the Ohtahara Syndrome is still not clearly understood. The different possible causes of Ohtahara Syndrome include metabolic disorders, neurological disorder,

malformation of the brain and certain defective genetic mutations. It has been observed that most of the infants suffering from Ohtahara Syndrome have the partial or incomplete development of the two sides of the brain (the cerebral hemispheres). brainstem alterations are also noticeable.

Abnormal genetic mutation can affect single gene or a group of the gene, which primarily responsible for brain development and neurological functioning. The responsible genes, which can cause Ohtahara Syndrome are ARX, ARHGEF9, BRAT1, CDKL5, KCNQ2, PCDH19, PLCB1, PNKP, SCN2A, SCN8A, SLC25A22, SPTAN1, STXBP1, ST3GAL3 and TBC1D24^1,4.

Diagnosis

Depending on the clinical presentation doctor could assume the presence of Ohtahara Syndrome. Other laboratory-based diagnoses include

• Assessment of electroencephalographic (EEG) findings. EEG of neonates suffering from Ohtahara Syndrome showed a ‘burst suppression pattern’ (characterized by discharge of high voltage spike wave). Burst suppression pattern means spikes amplitude is elevated, which then pursue with little brain activity followed by brain waves flattening). This neurological pattern is followed both in sleeping and awakening condition of the affected infants. Ohtahara Syndrome also evokes by the abnormal brainstem.
• Neuroimaging tests are conducted for the evolution of brain structural abnormalities. Magnetic Resonance Imaging ( MRI) is typically used for diagnosis of Ohtahara Syndrome. At the initial stage, MRI reports show normal findings, but shrinkage or atrophy of nerves in the brain appear on the follow-up MRIs. Abnormal findings of MRI is detectable by neurologists and they provide the inference of the Ohtahara Syndrome presence.
• A hematological assessment also requires for detecting genetic and/or metabolic abnormality^1,4,5.

Treatment

Subjective evidence only recommended specific anti-epileptic drugs to control the condition. However, different anti-epileptic drugs, including phenobarbital, pyridoxine, valproate, zonisamide, and benzodiazepines showed limited benefits to control the seizure attacks in Ohtahara syndrome.

Adrenocorticotropic hormone therapy also recommended to patients who have progressive Ohtahara syndrome and produce West syndrome, but limited efficacy in only Ohtahara syndrome.

• Antiepileptic medications, adrenocorticotropic hormone therapy, pyridoxine, and corticosteroids, do not produce any effective result to control early myoclonic encephalopathy and also inefficient to seizure management.
• The underlying metabolic disorder correction can provide a better outcome, which includes biotinidase deficiencies or pyridoxine deficiency correction.
• Dextromethorphan, sodium benzoate and ketamine alone or in combination with imipramine, tryptophan, or strychnine can use for managing myoclonic encephalopathy associated with nonketotic hyperglycinemia.
• A medical device which can stimulate vagus nerve may apply for those patients who are not responding to treatment with medicines.
• The ketogenic diet may also recommend for children suffering from Ohtahara Syndrome.

The above-mentioned treatment plan can provide temporary benefits, but no beneficial long-term outcomes observe.

• Surgical interventions including neurosurgery with hemispherectomy or focal resection can provide a better outcome in patients suffering from cortical dysplasia or hemimegaloencephaly^1,4,6,7,8.

Prognosis

Very poor prognosis is associated with Ohtahara Syndrome, as fatality during infancy is the most common outcome. The impaired psychomotor functioning with or without frequent seizure attack is responsible for poor prognosis. In the case of a child, survive for a period of time has severely handicapped^1,3.

Life Expectancy

Neonates having Ohtahara Syndrome have a very short lifespan. Most of the infants having Ohtahara Syndrome die within their infancy¹.

References

1. Ohtahara Syndrome, Epilepsy Foundation, Retrieve from http://www.epilepsy.com/learn/types-epilepsy-syndromes/ohtahara-syndrome
2. Ohtahara Syndrome, International League Against Epilepsy; https://www.epilepsydiagnosis.org/syndrome/ohtahara-overview.html
3. Ohtahara Syndrome; National Institute Of Neurological Disorders and stroke; https://www.ninds.nih.gov/Disorders/All-Disorders/Ohtahara-Syndrome-Information-Page
4. Jules C. Beal, Koshi Cherian, Solomon L. Moshe, Early-Onset Epileptic Encephalopathies: Ohtahara Syndrome and Early Myoclonic Encephalopathy; http://dx.doi.org/10.1016/j.pediatrneurol.2012.06.002; http://www.sciencedirect.com/science/article/pii/S0887899412002688
5. Djukic, F.A. Lado, S. Shinnar, S.L. Moshé; Are early myoclonic encephalopathy (EME) and the Ohtahara syndrome (EIEE) independent of each other?; Epilepsy Res, 70 (2006), pp. 68–76
6. M. Ohno, Y. Shimotsuji, J. Abe, M. Shimada, H. Tamiya, Zonisamide treatment of early infantile epileptic encephalopathy, Pediatr Neurol, 23 (2000), pp. 341–344
7. H. Tekgul, G. Serdaroglu, B. Karapinar, et al.; Vigabatrin caused rapidly progressive deterioration in two cases with early myoclonic encephalopathy associated with non ketotic hyperglycinemia; J Child Neurol, 21 (2006), pp. 82–84
8. M. Ishii, M. Shimono, A. Senju, K. Kusuhara, N. Shiota; The ketogenic diet as an effective treatment for Ohtahara syndrome; No To Hattatsu, 43 (2011), pp. 47–50