ohtahara syndrome is a devastating infantile epileptic encephalopathy , which has an onset within the first few weeks of life , is associated with predominantly tonic seizures , and shows suppression - burst background on eeg .
it is one of the epileptic encephalopathies that are characterized by frequent and medically intractable seizures , along with a significant burden of interictal epileptiform activity , which may contribute to a progressive and often catastrophic neurodevelopmental outcome .
these disorders are classified based on their electroclinical characteristic ( i.e. , age at onset , seizure type and eeg pattern ) .
seizures of patients with epileptic encephalopathies are often resistant to antiepileptic drug therapies , but may respond to a ketogenic diet .
the ketogenic diet is a high fat , low carbohydrate , and restricted protein diet that has been shown to be particularly useful in some epileptic encephalopathies such as west syndrome , infantile spasms , dravet syndrome , , and lennox  gastaut syndrome .
however , its efficacy in ohtahara syndrome has rarely been reported , and to the best of our knowledge , there is only one isolated case report .
we report a case with ohtahara syndrome that showed remarkable and sustained response for close to one year post - initiation of ketogenic diet .
our patient is a five - year - old child , full term product of a normal spontaneous vaginal delivery .
seizure onset was at 2  weeks of age and was initially attributed to reflux .
he then began to have overt seizures , characterized by generalized tonic stiffening , which occurred multiple times per day .
generalized tonic  in nature , occurring approximately 2030 times daily , sometimes up to 50 .
an initial eeg showed suppression - burst background and several tonic seizures characterized by an electrodecremental response .
a full metabolic work - up , genetic studies ( arx and cdkl5 ) , and magnetic resonance imaging of the brain were all normal , and he was presumptively diagnosed with ohtahara syndrome based on the electroclinical characteristics .
seven subsequent eegs were performed over a period of four years , and all showed predominantly suppression - burst background with several tonic seizures .
his further development was severely impaired and complicated by numerous medical issues such as severe sleep apnea with frequent oxygen desaturations and recurrent aspiration pneumonia requiring tracheostomy .
goals of care were addressed at each visit , and all medical decisions were made by his mother . at baseline , he focused but did not follow , was able to cry and smile to communicate , did not roll or hold objects or sit , and was in a diaper and completely gastric ( g ) tube fed .
he required frequent hospitalizations due to recurrent infections and worsening seizures , which were refractory to every known antiepileptic drug regimen including a course of steroids and trial with pyridoxine .
a recent eeg in early 2014 showed a suppression - burst background , which was more prominent in sleep and characterized by the absence of sleep structures ( fig .  1 , fig .  2 ) .
a small portion ( approximately 10% ) of his waking background comprised of spike and slow wave discharges .
in addition , in the epilepsy monitoring unit , we captured 19 seizures in a 12-hour study , all characterized by generalized tonic stiffening and an electrodecremental response on eeg .
given his lack of response to medication trials , ketogenic diet was initiated in february 2014 with a goal ratio of 4:1 ( ratio of grams of fat to grams of protein plus carbohydrate ) .
he tolerated the diet well , ketosis was achieved on day four , and he was discharged home .
his mother reported a remarkable improvement in seizure frequency on subsequent follow - up via office visits or phone calls .
one month post - diet initiation , he was having 03 seizures per day , which was a significant improvement from 2030 seizures per day .
he has not had a single visit to the emergency room ( er ) in the last one year , which is a significant improvement from multiple seizure - related visits to the er the previous year .
this improvement was confirmed via a repeat admission to our epilepsy - monitoring unit in february 2015 .
his eeg background during this admission was unchanged when compared to his prior study a year ago , but we captured only 2 brief tonic seizures , lasting for approximately 10  s each , in a 24-hour period of monitoring .
ohtahara syndrome is one form of early infantile epileptic encephalopathy with medically intractable seizures and progressive neurodevelopmental deterioration .
first described by ohtahara et al . in 1976 , it is an electroclinical syndrome characterized by tonic spasms and a suppression - burst pattern on eeg .
electroencephalography of most patients with ohtahara syndrome transitions into hypsarrhythmia at approximately 3 to 6  months of age , and later into diffuse slow spike waves .
most survivors of ohtahara syndrome show an eeg with focal or multifocal spikes , and suppression - burst pattern rarely persists beyond an age of one year . to our knowledge
, there is an isolated case report describing the persistence of suppression - burst pattern in a five - year - old girl with ohtahara syndrome   and one reported case of an infant with ohtahara syndrome who responded to ketogenic diet , but the degree and duration of response is not known .
we describe a patient with ohtahara syndrome who has survived to the age of five years , and who continues to show suppression - burst pattern on eeg , with sustained improvement in seizure frequency for one year post - initiation of ketogenic diet . increased prominence of suppression - burst pattern with sleep and a small portion of his waking background comprising of spike and slow wave discharges might suggest transition into west syndrome or lennox  gastaut syndrome .
however , we did not find any sleep structures or hypsarrhythmia during the waking state , a large portion of his eeg continues to show a suppression - burst pattern in awake or asleep states , and he almost exclusively has tonic seizures , which is commonly reported in patients with ohtahara syndrome .
patients with this syndrome invariably have intractable seizures and are developmentally devastated . after initiating ketogenic diet in our patient , not only did his seizure frequency improve significantly , but there was also a clear improvement noted in his level of interaction and temperament .
this could arguably have been a spontaneous remission in the course of his disease , and the only way to answer that question would be to stop the diet ( to which he has responded so well ) and observe any worsening of his seizure frequency .
this step was considered unethical , so we did not attempt it . given the low incidence rate of ohtahara syndrome , the strength of evidence might never be sufficient enough to recommend any treatment modality .
in addition , determining what constitutes  reasonable quality of life  can be an endless ethical debate in this subset of patients , but any intervention that can control seizures and make them more interactive is probably worth trying .
as analyzed all patient data and was a major contributor in writing the manuscript . in was involved with checking the accuracy of the ketogenic diet regimen .
cc helped gather patient data over the years and was responsible for obtaining consent from patient 's family .
rhm is the primary caretaker , and has reviewed and revised the article ensuring accuracy of intellectual content .
the authors received no financial support for the research , authorship , and/or publication of this article .
the authors declared no potential conflicts of interest with respect to the research , authorship , and/or publication of this article .
 ketogenic diet has been shown to be efficacious in some epileptic encephalopathies but rarely reported as being useful in children with ohtahara syndrome . 
 this could possibly be attributed to the rarity of the disease and associated short survival period . 
 we report on a 5-year - old child with ohtahara syndrome , whose seizures failed to improve with all known medications , continued to show persistent suppression - burst pattern on the electroencephalography ( eeg ) and had substantial reduction in seizure frequency for one year post - initiation of ketogenic diet . he has not had a single visit to the emergency room because of seizures in the last one year , and more importantly , there has been a clear improvement noted in his level of interaction and temperament . 
 patients with ohtahara syndrome invariably have medically intractable seizures and catastrophic neurodevelopmental outcome . 
 ketogenic diet is a treatment modality that might be worth considering even in this group of patients . 