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although medical therapy is the mainstay for epilepsy , approximately 30% of patients are intractable . the efficacy of open surgery for intractable medial temporal lobe epilepsy ( mtle ) compared to prolonged medical therapy has been proven and it has become the treatment of choice for the treatment of intractable mtle .
long - term follow - up results of more than 5 years reported that the seizure - free rate after resection surgery was approximately 5070% .
the mortality rate is less than 1% , and the rate of major complications ranges from 1 to 4% .
since stereotactic radiosurgery revealed seizure control effect for cerebral arteriovenous malformations or tumors , gamma knife radiosurgery ( gks ) has been proposed as an alternative option to open surgery for mtle .
non - invasiveness and safety are major advantages of gks over open surgery . on the other hand ,
for this reason , the clinical significance of gks for mtle has been the subject of controversy . in this report
, we report a case of an 18-year - old male patient with intractable mtle treated with fractionated gks , which reduced the adverse effects of single fractioned gks and improved cognitive function with seizure free outcome .
the patient was an 18-year - old left handed male with a history of infantile febrile seizures that had spontaneously resolved at 8-years - of - age .
he had no family history of seizures and was born by vaginal delivery without any perinatal problems .
complex partial seizures , sometimes with secondary generalization , started without specific cause at 14-years - of - age .
the current seizure episodes were initiated by a rising sensation in the epigastrium followed by nausea and vomiting , loss of awareness , turning of his head to the left , and drooling .
a variety of anti - epileptic drugs including topiramate , levetiracetam , rebamipide and oxcarbazepine were prescribed , but failed to control the seizures .
he was referred to our institution for evaluation of temporal lobe surgery for the medical refractory seizures .
he underwent preoperative evaluation including a neurological examination , scalp video - electroencephalogram ( eeg ) monitoring , high - resolution magnetic resonance imaging ( mri ) , f - deoxyglucose positron emission tomography ( fdg - pet ) , and a neuropsychological test .
ictal eeg demonstrated evolution from rhythmic delta wave to sharp wave in the left temporal area , suggesting left temporal onset epilepsy . a spike and intermittent semirhythmic slow activity in the left temporal area was shown in interictal eeg ( fig .
gadolinium - enhanced mri showed left hippocampal sclerosis with slightly decreased volume and increased t2 signal ( fig .
fdg - pet showed mild hypometabolism in the left temporal lobe compared to the right side .
neuropsychological test revealed moderate mental retardation ( iq , 50 ; viq , 55 ; piq , 59 ) and diffuse cerebral dysfunction in both frontal and temporal lobes ( table 1 ) .
he showed decreased attention ability with a borderline degree of impairment , and declined ability of storage and withdrawal memory . in language tests , spontaneous speech , auditory comprehension , reading , writing , and sequential commands were normal , but repetition and naming were impaired .
the epilepsy committee consisting of a neurologist , neurosurgeon , and others recommended gks instead of open surgery .
the patient underwent fractionated gks after understanding that the seizures may or may not respond to treatment and that the antiepileptic drugs therapy would be continued for at least 2 years .
fractionated gks was performed under local anesthesia , using the leksell gamma knife ( model b elekta instrument ab ) with leksell gamma plan ( elekta , stockholm , sweden ) .
treatment planning was based on the combination of computed tomography ( ct ) and mri to cover the amygdala , hippocampal head and body , most of the parahippocampal gyrus , and the entorhinal cortex ( fig .
the target region of 8.8 cm volume received marginal dose of total 24 gy in 3 fractionations on 3 consecutive days with a dose of 8 gy at the 50% isodose line ( maximum dose 16.1 gy ) .
he was maintained on anti - seizure medications including topiramate , levetiracetam , and oxcarbazepine . during the first month
however , the frequency of seizure episodes began to increase again at 1 month post - gks .
although mri obtained at post - gks 6 months showed no significant interval change except slightly decreased volume of the lift hippocampus , the seizure frequency increased to reach 6 times per month at 9 months post - gks .
afterward , further seizure activity or residual auras disappeared . at 11 months after gks ,
the patient visited the hospital due to a severe headache without recurrence of seizure episodes .
follow - up t2-wi mri revealed 2-cm sized round central low signals with surrounding high signals around the left hippocampus , which suggested radiation - induced changes ( fig .
an eeg performed 18 months after gks revealed moderate amount of intermittent generalized theta slow activity without epileptiform discharges , suggesting diffuse cerebral dysfunction .
he has continued to be seen by the neurologist and neurosurgeon and has remained free of complex - partial seizures of engel class i. eeg obtained at 30 months after gks showed no focal / generalized slow activity or epileptiform discharges , in accord with normal finding ( fig .
the patient showed improvement in general intelligence ( iq , 5070 ; viq , 5570 ; piq , 5975 ) , attention , memory , and motor function ( table 1 ) .
he did not show any significant change in language and frontal lobe function ( table 1 ) .
the patient has been free from seizures since 9 months after gks , and the dosages of antiepileptic drugs have been tapered .
since gks for mtle was first performed by rgis et al . , it has been used as a less invasive treatment option for mtle .
the authors reported that 65% of patients who underwent single fractionated gks by 25 gy to the 50% isodose obtained seizure - free at 2 years after gks in a prospective multicenter study .
the marseilles group also published 8-year follow - up results of 15 patients treated with 24 gy to the 50% isodose line .
nine of the patients obtained seizure - free , but seizure recurred in patients whose medication had been tapered or discontinued .
previous authors had suggested that radiosurgery induces biochemical changes resulting in a decrease of excitatory amino acids with gamma aminobyturic acid stability and inhibition of seizure production .
the results reported by rgis et al . as well as the multicenter , prospective pilot study in the phase iii radiosurgery or open surgery for epilepsy ( rose ) clinical trial suggested that the seizure outcome and complications of radiosurgery were similar comparable with those of open surgery . on the other hand , srikijvilaikul et al . failed to prove seizure control using a single fractionated gks in 5 patients who underwent radiosurgery with 20 gy to the 50% isodose .
two patients died of a consequence of seizures , and the remaining 3 patients had no benefit until 1.5 years after radiosurgery .
low dose might be one of the causes of the discrepancy of seizure outcome in previous reports of unsatisfactory seizure outcome . in the study of barbaro et al .
, the group randomized to 24 gy had a higher proportion of seizure remission than those to randomized to 20 gy for single fractionated gks .
radiosurgery can induce necrosis and consequent destruction of the epileptic focus and its pathways of spread .
however , the dose of radiosurgery is a double - edged sword ; single fractionated gks with sufficiently high dose could obtain satisfactory seizure control effect , but it might lead to fatal adverse effects . to resolve the dilemma double - edged sword fractionated gks , which aims to integrate the advantages of fractionated conventional radiotherapy and single - session radiosurgery can be considered as an ideal alternative option for the control of medically refractory mtle .
radiation delivered accurately permits larger doses to be delivered to larger areas without increasing the complication rate .
presently , the target volume of 8.8 cm contained the entire amygdala , hippocampal head and body , most of the parahippocampal gyrus , and the entorhinal cortex .
in contrast , the target volume in previous studies included the amygdala sparing the upper and mesial part , the head and anterior half of the body of the hippocampus , and the anterior part of the parahippocampal gyrus .
reducing dose per fraction could be an attractive alternative with minimizing adverse radiation effects and preserving the remaining function of medial temporal structures .
as far as we know , this is the first case report of the use of fractionated gks for mtle , although heikkinen et al . reported a patient with tle who was successfully treated without any clinical or radiological complications by fractionated radiotherapy with a total dose equivalent to 10 gy in 1992 .
our patient obtained seizure control at 9 months after gks . during the interval period between gks and seizure remission , he experienced temporarily increased seizure frequency and underwent constant medical treatment .
this delay in seizure control effects is one of the critical drawbacks of gks for mtle . in previous studies , the average duration until seizure control ranges from 10 to 12 months . during this period ,
if a patient can not tolerate the disabling seizures until seizure control , transition to open surgery should be considered .
the patient experienced mild degree of radiation induced changes in the follow up brain mri at 11 months after gks and symptoms relieved by short - term steroid therapy in contrast to the severe adverse reactions reported in the previous studies .
the radiological finding was accompanied by newly appeared headache , without recurrence of seizure episodes .
post - radiosurgical t2 hyperintensity lesion , contrast enhancement , and surrounding vasogenic edema have been reported to appear approximately 9 months to 1 year after gks and gradually regressed within a few years . at 24 months ,
the radiation - induced mri changes have been associated with the transient increase in seizure frequency , which did not happen with our case .
newly developed headaches have been known to be noted in 70% of cases with post - radiosurgical mri changes , and are well controlled by steroids .
the patient experienced unexpected favorable clinical outcomes in terms of cognitive function proved by neuropsychological test ( table 1 ) .
srikijvilaikul et al . also reported no significant memory decline at a group level 6 months after radiosurgery , but they found significant declines in specific cognitive domains in 3 of 4 of their patients .
. reported on 3 patients treated on the language - dominant side during the period of development of the radiosurgical lesion .
significant impairment in at least one measure of verbal memory with sparing of iq , visual memory , and language was evident .
a notable finding is that a worse neuropsychological outcome was found in patients irradiated with higher doses . in the patients who obtained seizure freedom ,
our experience with this patient suggests the efficacy of the fractionated gks to improve cognitive outcome in patients with mtle .
the patient achieved not only seizure control at 9 months after gks , but also improvement of cognitive function .
this case report suggests that fractionated gks could be considered as a safe tool to achieve the better outcome in seizure control and neuropsychological improvement for patients with mtle .
further long - term prospective studies with a larger numbers of patients are needed to determine the optimal doses and fraction schedules of fractionated gks for mtle .
an 18-year - old left - handed male harbored intractable medial temporal lobe epilepsy ( mtle ) underwent fractionated gamma knife surgery ( gks ) instead of open surgery , considering the mental retardation and diffuse cerebral dysfunction . 
 gks treatment parameters were : target volume , 8.8 cm3 ; total marginal dose , 24 gy in 3 fractionations at the 50% isodose line . 
 the patient has been free from seizures since 9 months after gks , with notable improvement in cognitive outcome . 
 fractionated gks could be considered as a safe tool for seizure control and neuropsychological improvement in patients with mtle .