Challenges in the management of a case of tuberous sclerosis
A 16-year-old adolescent male, a Sikh by religion and educated up to 2nd 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.\nHistory 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. There has been no seizure free period since the onset of seizures. 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.\nThe 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.\nGeneral physical and systemic examination was within normal limits apart from the findings of facial angiofibromas [] in the facial region. His body weight was 65 kg. Mental status examination was suggestive of low cognitive profile and did not reveal any other psychopathology.\nComputed 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 and ]. Electroencephalogram (EEG) of the patient was non-specific.\nManagement of the patient was carried out keeping in mind the following objectives:\nControl 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.\nAs 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. Valproate was increased to 2 g/day in divided doses. 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.\nThe 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.\nThe 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. These investigations were within normal limits.\nA 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. This resulted in visible reduction in the facial angiofibromas. No major adverse effects were noted except transient burning sensation at the site of application.