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Everolimus and intensive behavioral therapy in an adolescent with tuberous sclerosis complex and severe behavior.

Gipson TT, Jennett H, Wachtel L, Gregory M, Poretti A, Johnston MV - Epilepsy Behav Case Rep (2013)

Bottom Line: Everolimus, an mTOR inhibitor, has been FDA-approved for subependymal giant cell astrocytomas (SEGAs) and renal angiomyolipomas in TSC.During an inpatient admission to a neurobehavioral unit, real-time measurements of behaviors and seizures were recorded.Mechanism-based treatments in the setting of an evidence-based behavioral and psychopharmacological intervention program may be a model with utility for characterization and treatment of individuals with severe behavior and TSC.

View Article: PubMed Central - PubMed

Affiliation: Tuberous Sclerosis Clinic, Kennedy Krieger Institute, Baltimore, MD, USA.

ABSTRACT

Background: Self-injury and aggression have been reported in individuals with TSC (tuberous sclerosis complex), yet few data exist about treatment. Everolimus, an mTOR inhibitor, has been FDA-approved for subependymal giant cell astrocytomas (SEGAs) and renal angiomyolipomas in TSC. However, clinical use of everolimus with direct, real-time observations of self-injury and aggression in an individual with TSC has not been reported.

Methods: During an inpatient admission to a neurobehavioral unit, real-time measurements of behaviors and seizures were recorded. An interdisciplinary team used these data to make treatment decisions and applied behavioral and pharmacological treatments, one at a time, in order to evaluate their effects.

Results: Aggression and self-injury improved with applied behavioral analysis (ABA), lithium, and asenapine. Improvements in SEGA size, facial angiofibromas, seizures, and the most stable low rates of self-injury were observed during the interval of treatment with everolimus.

Conclusion: Mechanism-based treatments in the setting of an evidence-based behavioral and psychopharmacological intervention program may be a model with utility for characterization and treatment of individuals with severe behavior and TSC.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of the mammalian target of rapamycin (mTOR) pathway and site of action of mechanism-based treatments.
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f0010: Schematic diagram of the mammalian target of rapamycin (mTOR) pathway and site of action of mechanism-based treatments.

Mentions: Aggression, self-injury, seizures, and SEGA size were targets of treatment in this case. Aggression was decreased by behavioral intervention, lithium, and asenapine. Severe seizures were the lowest when treated with everolimus and oxcarbazepine, and the frequency increased to baseline levels when everolimus was discontinued. Everolimus and lithium, two of the treatments used in this case, are both directly involved in the underlying neurobiology of TSC. Everolimus directly inhibits abnormally elevated mTOR activity associated with mTORC1, and lithium inhibits inositol-1-phosphate, which would typically increase activity of mTORC2 (Fig. 2). Everolimus has been FDA-approved for treatment of SEGAs and renal angiomyolipomas (AMLs) in TSC; however, the effects of everolimus on behavior and seizures have not been systematically studied. In contrast, the efficacious usage of lithium in aggressive behavioral disorders has been reported for decades. Early studies of lithium's utility in manic–depressive illness concomitantly showed significant reduction of aggression in animal models [3], and the benefit of lithium in youth with severe aggression and intellectual disability quickly appeared in the literature [4,5]. Similarly, behavioral interventions have a large body of literature supporting their effectiveness in reducing problem behavior in individuals with autism spectrum disorders and intellectual disabilities [6].


Everolimus and intensive behavioral therapy in an adolescent with tuberous sclerosis complex and severe behavior.

Gipson TT, Jennett H, Wachtel L, Gregory M, Poretti A, Johnston MV - Epilepsy Behav Case Rep (2013)

Schematic diagram of the mammalian target of rapamycin (mTOR) pathway and site of action of mechanism-based treatments.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150649&req=5

f0010: Schematic diagram of the mammalian target of rapamycin (mTOR) pathway and site of action of mechanism-based treatments.
Mentions: Aggression, self-injury, seizures, and SEGA size were targets of treatment in this case. Aggression was decreased by behavioral intervention, lithium, and asenapine. Severe seizures were the lowest when treated with everolimus and oxcarbazepine, and the frequency increased to baseline levels when everolimus was discontinued. Everolimus and lithium, two of the treatments used in this case, are both directly involved in the underlying neurobiology of TSC. Everolimus directly inhibits abnormally elevated mTOR activity associated with mTORC1, and lithium inhibits inositol-1-phosphate, which would typically increase activity of mTORC2 (Fig. 2). Everolimus has been FDA-approved for treatment of SEGAs and renal angiomyolipomas (AMLs) in TSC; however, the effects of everolimus on behavior and seizures have not been systematically studied. In contrast, the efficacious usage of lithium in aggressive behavioral disorders has been reported for decades. Early studies of lithium's utility in manic–depressive illness concomitantly showed significant reduction of aggression in animal models [3], and the benefit of lithium in youth with severe aggression and intellectual disability quickly appeared in the literature [4,5]. Similarly, behavioral interventions have a large body of literature supporting their effectiveness in reducing problem behavior in individuals with autism spectrum disorders and intellectual disabilities [6].

Bottom Line: Everolimus, an mTOR inhibitor, has been FDA-approved for subependymal giant cell astrocytomas (SEGAs) and renal angiomyolipomas in TSC.During an inpatient admission to a neurobehavioral unit, real-time measurements of behaviors and seizures were recorded.Mechanism-based treatments in the setting of an evidence-based behavioral and psychopharmacological intervention program may be a model with utility for characterization and treatment of individuals with severe behavior and TSC.

View Article: PubMed Central - PubMed

Affiliation: Tuberous Sclerosis Clinic, Kennedy Krieger Institute, Baltimore, MD, USA.

ABSTRACT

Background: Self-injury and aggression have been reported in individuals with TSC (tuberous sclerosis complex), yet few data exist about treatment. Everolimus, an mTOR inhibitor, has been FDA-approved for subependymal giant cell astrocytomas (SEGAs) and renal angiomyolipomas in TSC. However, clinical use of everolimus with direct, real-time observations of self-injury and aggression in an individual with TSC has not been reported.

Methods: During an inpatient admission to a neurobehavioral unit, real-time measurements of behaviors and seizures were recorded. An interdisciplinary team used these data to make treatment decisions and applied behavioral and pharmacological treatments, one at a time, in order to evaluate their effects.

Results: Aggression and self-injury improved with applied behavioral analysis (ABA), lithium, and asenapine. Improvements in SEGA size, facial angiofibromas, seizures, and the most stable low rates of self-injury were observed during the interval of treatment with everolimus.

Conclusion: Mechanism-based treatments in the setting of an evidence-based behavioral and psychopharmacological intervention program may be a model with utility for characterization and treatment of individuals with severe behavior and TSC.

No MeSH data available.


Related in: MedlinePlus