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Paper text:
a 16-year - old adolescent male , a sikh by religion and educated up to 2 standard , belonging to a middle socio - economic status with non - vegetarian dietary habits was brought to our psychiatry outpatient department by parents with chief complaints of generalized tonic - clonic seizures since 2 years of age , low - intelligence since childhood and behavior problems like stubbornness and aggression since past 5 - 6 years .
history of present illness revealed uneventful prenatal and perinatal course along with delayed motor , speech , and adaptive milestones .
the patient had his first episode of grand - mal seizures at around 2 years of age and has been having them regularly since then but with variable frequency and duration .
the patient started going to a school at around 6 years of age but discontinued studies after 2 years of age due to poor performance at school and being ridiculed by his peers for poor performance and for marks on his face .
the patient would spend most of the time at his home playing with his younger siblings and occasionally playing with other younger children in his neighborhood .
for the past 5 - 6 years the parents have noticed increasing behavior problems like stubbornness and not following parental instructions along with frequent episodes of verbal aggression and occasional episodes of physical aggression mostly directed towards parents and younger siblings generally when his wishes were thwarted or demands were not met .
the patient had been shown to many doctors ever since his seizures started and his treatment prescriptions showed that for past 1 year he had been taking orally sodium valproate 500 mg twice daily , phenobarbital 60 mg twice daily , carbamazepine 200 mg thrice daily , and clonazepam 0.5 mg twice daily .
the family reported only a small decrease in seizure frequency even after taking these medications .
there was no history of any co - morbid medical and surgical illness in the patient or any history of similar features in any of the family members .
general physical and systemic examination was within normal limits apart from the findings of facial angiofibromas [ figure 1 ] in the facial region .
mental status examination was suggestive of low cognitive profile and did not reveal any other psychopathology .
facial angiofibromas ( adenoma sebaceum ) computed tomography scan and magnetic resonance imaging of the patient displayed multiple subependymal nodules and small multifocal discreet lesions in bilateral cerebral hemispheres suggestive of cortical and sub - cortical tubers [ figures 2 and 3 ] .
computed tomography scan findings of the patient showing sub - ependymal nodules magnetic resonance imaging revealing small multifocal discreet tubers in bilateral cerebral hemispheres management of the patient was carried out keeping in mind the following objectives : 
 control of grand mal seizures through optimization of treatment regimeassessment of patient 's cognitive abilities and achievement of optimum level of adaptive functioning according to patient 's cognitive abilitiesbehavioral modification aimed at reduction of undesirable behaviors and promotion of adaptive and socially desirable behaviorsdetection and timely treatment of other manifestations of tuberous sclerosis to prevent complications . 
 
control of grand mal seizures through optimization of treatment regime assessment of patient 's cognitive abilities and achievement of optimum level of adaptive functioning according to patient 's cognitive abilities behavioral modification aimed at reduction of undesirable behaviors and promotion of adaptive and socially desirable behaviors detection and timely treatment of other manifestations of tuberous sclerosis to prevent complications . as part of the management plan
, the patient 's medications were optimized and he was started on a single anti - epileptic drug sodium valproate at the dosage of 1000 mg / day ( 15 mg / kg / day ) .
the rationale behind this step was that the patient 's current medications regime comprised of multiple anti - epileptics medications two of which were enzyme inducers , i.e. , carbamazepine and phenobarbital , which were reducing the effective dose of sodium valproate as well as carbamazepine resulting in reduced plasma levels .
it was decided to subsequently adjust the dose of sodium valproate during subsequent follow - ups and to increase the dose gradually depending on the patient 's tolerability and response to a maximum of 60 mg / kg body weight .
though , the patient 's seizure frequency decreased markedly on this dose but he was not completely seizure free .
any effort to increase the dose of valproate resulted in intolerable gastrointestinal ( gi ) side - effects .
therefore , clobazam 10 mg / day was added to valproate and this resulted in complete improvement of patient 's seizures . currently , he is seizure free for past 2 months .
the patient 's cognitive assessment ( for intelligence quotient ( iq ) assessment first parents were interviewed for development behavior on  vineland social maturity scale  and then child was evaluated first on  seguin form board test  and then on  colored progressive matrices .  for cognitive assessment 
bender gestalt test  and  weschler memory scale  were done ) revealed an iq of 45 , i.e. , moderate mental retardation and a mental age of approximately 7 years with relative strength in visual - spatial domain .
parents and family members were psycho - educated regarding the patient 's limited cognitive abilities and to lower down their expectations from the patient to bring it in coherence with the patient 's cognitive abilities .
behavior therapy was started to reduce the frequency and duration of undesirable behaviors and to promote desirable behaviors by using the principles of negative and positive re - enforcement .
the patient was given remedial education and was started from his current level of knowledge .
after 3 months of behavior therapy and remedial education , there was marked improvement in the patient 's behavior as evidenced by reduced frequency and duration of anger episodes and reduced need for help in daily routine activities . by the end of 3 months , the patient was able to read road signs in english and hindi and write his name in both the languages and was able to do simple addition and subtraction problems .
the patient also underwent following investigations : complete hemogram , liver function tests , renal function tests , ultrasonogram whole abdomen , echocardiography , and ophthalmic examination including , retinal and fundus examination .
this was carried out to detect any other systemic manifestations of tuberous sclerosis , which might need treatment .
a dermatological consultation was also carried out for the treatment of cosmetically disfiguring facial angiofibromas since that was adding to the social embarrassment of the patient .
the patient was started on tacrolimus 0.1% w / w ointment for topical application on the affected area .
no major adverse effects were noted except transient burning sensation at the site of application .
this case highlights the treatment challenges faced in the management of a patient suffering from tuberous sclerosis .
it is evident that management of tuberous sclerosis requires a multi - disciplinary approach and an ongoing assessment for the timely management of complications that arise with increasing age .
unfortunately , majority of such patients do not have access to such multi - disciplinary team at one place .
however , a systematic approach to such patients can result in the optimum utilization of abilities of these patients and their integration in the mainstream society in a cost - effective way .
it is clear that both pharmacological and non - pharmacological aspects of treatment like psycho - education and involving the family in the treatment process are important in the whole management plan .
the goals of treatment for patients with tsc are providing the best possible quality of life with the fewest complications from the underlying disease process , fewest adverse treatment effects , and minimum number of drugs .
the major complication of tsc requiring long - term medical treatment is epilepsy but no single drug gives satisfactory relief for most of the cases . a combination of drugs is frequently required .
the choice of specific anti - epileptic drugs ( aed ) for treating seizures in patients with tsc is based on the patient 's seizure type ( s ) , epilepsy syndrome ( s ) , other involved organ systems , age of the patient , and aed side effect profiles and formulations available .
though , vigabatrin is considered as the drug of choice for children with tsc and infantile spasms .
benzodiazepines or barbiturates should be avoided as these drugs often aggravate underlying behavioral or cognitive problems .
carbamazepine , oxcarbazepine , and phenytoin may cause exacerbation of seizures , particularly in younger children and infants , and these aeds can aggravate infantile spasms . in the present case , initially
the combination of carbamazepine , phenobarbitone , valproate and clonazepam and later on , valproate alone were ineffective in controlling seizures .
finally , the combination of valproate and clobazam was found to be effective in controlling seizures .
rapamycin is a new immunosuppressant with a propensity to inhibit t - cell proliferation and has been approved for use in treating facial angiofibromas in tsc patients without significant adverse effects .
there is need of formulation of optimum evidence - based guidelines for the management of such patients .
tuberous sclerosis complex is a multi - system disorder with autosomal dominant inheritance , which can affect the brain , heart , skin , kidneys , lungs , and retina . 
 we hereby report therapeutic challenges faced in a case of an adolescent male suffering from tuberous sclerosis .