Tuberous sclerosis associated with MDR1 gene expression and drug-resistant epilepsy

Pediatr Neurol. 1999 Oct;21(4):731-4. doi: 10.1016/s0887-8994(99)00074-0.


Intractable seizures are the most common manifestation in severe cases of tuberous sclerosis. Multidrug resistance type 1 (MDR1) gene expression is directly linked to the resistance of tumor cells to chemotherapy as the major cause of treatment failure, but it has not been reported in tuberous sclerosis cells nor has the relationship between the MDR1 gene and antiepileptic drugs been described. A 4-month-old female is described with poorly controlled seizures secondary to tuberous sclerosis. The patient was treated with antiepileptic drugs, including phenytoin, phenobarbital, and lorazepam, without improvement of symptoms. Phenytoin blood levels were invariably subtherapeutic and ranged from 0.45 to 3.55 microg/mL, despite several consecutive intravenous loading doses. Surgical treatment with total resection of the brain lesions was performed as a last resort. Immunohistochemical analysis of the resected tissues revealed high levels of P-glycoprotein 170 expression, the product of the MDR1 gene. Both MDR1 gene expression and persistently low phenytoin levels likely share a common pathway liable to induce drug-resistant epilepsy.

Publication types

  • Case Reports

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Anticonvulsants / therapeutic use*
  • Biopsy
  • Brain / metabolism*
  • Brain / pathology
  • Brain / surgery
  • Drug Resistance, Multiple / genetics*
  • Epilepsy / drug therapy
  • Epilepsy / genetics*
  • Female
  • Gene Expression
  • Genes, MDR / genetics
  • Humans
  • Immunohistochemistry
  • Infant
  • Treatment Outcome
  • Tuberous Sclerosis / complications
  • Tuberous Sclerosis / genetics*


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anticonvulsants