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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

Magnetic resonance imaging of subependymal giant cell astrocytoma (SEGA) before and after treatment with everolimus. Pretreatment (A) axial and (B) coronal and (C) axial and (D) coronal 3D-T1-postcontrast-weighted images after 5-month treatment with everolimus show a mild reduction in size of the SEGA.
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f0005: Magnetic resonance imaging of subependymal giant cell astrocytoma (SEGA) before and after treatment with everolimus. Pretreatment (A) axial and (B) coronal and (C) axial and (D) coronal 3D-T1-postcontrast-weighted images after 5-month treatment with everolimus show a mild reduction in size of the SEGA.

Mentions: During the functional analysis process, medical attention focused primarily on management of epilepsy. Admission medications included oxcarbazepine, tranxene (a benzodiazepine derivative), vigabatrin, and melatonin. Oxcarbazepine and vigabatrin were continued, and abortive treatment (rectal diazepam or nasal midazolam) was added for single seizures lasting longer than 5 min or a cluster of three or more seizures lasting at least 30 s in a 24-hour period. These seizures requiring diazepam or midazolam either due to duration or total number in 24 h were classified as “severe seizures” and documented separately. The percentage of severe seizures during baseline was 23.8% (5/21) while taking vigabatrin and oxcarbazepine over 8 weeks. Ictal activity was suspected near the SEGA in the right frontal lobe; therefore, everolimus treatment was initiated to reduce the size of the SEGA. A confirmatory EEG was not feasible because of the severity of behaviors. Dose titration and serum level monitoring were conducted in accordance with FDA-approved guidelines [1,2]. Overall, data recorded during therapeutic serum levels of everolimus revealed a slight decrease in size of the SEGA (Fig. 1), decreased frequency of severe seizures, and improvement in facial angiofibromas. Severe seizures decreased to 8% (3/39) during 12 weeks of everolimus at therapeutic serum levels (5–15 ng/ml) and oxcarbazepine. After discontinuation of everolimus due to parental concern regarding an adverse event (pneumonia), frequency of severe seizures increased to 21% (6/29) over 8 weeks with oxcarbazepine alone. Other antiepileptic medication changes included weaning of vigabatrin and addition of rufinamide. These changes did not affect seizures, and rufinamide was discontinued after 2 weeks because of increased aggression and agitation.


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)

Magnetic resonance imaging of subependymal giant cell astrocytoma (SEGA) before and after treatment with everolimus. Pretreatment (A) axial and (B) coronal and (C) axial and (D) coronal 3D-T1-postcontrast-weighted images after 5-month treatment with everolimus show a mild reduction in size of the SEGA.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0005: Magnetic resonance imaging of subependymal giant cell astrocytoma (SEGA) before and after treatment with everolimus. Pretreatment (A) axial and (B) coronal and (C) axial and (D) coronal 3D-T1-postcontrast-weighted images after 5-month treatment with everolimus show a mild reduction in size of the SEGA.
Mentions: During the functional analysis process, medical attention focused primarily on management of epilepsy. Admission medications included oxcarbazepine, tranxene (a benzodiazepine derivative), vigabatrin, and melatonin. Oxcarbazepine and vigabatrin were continued, and abortive treatment (rectal diazepam or nasal midazolam) was added for single seizures lasting longer than 5 min or a cluster of three or more seizures lasting at least 30 s in a 24-hour period. These seizures requiring diazepam or midazolam either due to duration or total number in 24 h were classified as “severe seizures” and documented separately. The percentage of severe seizures during baseline was 23.8% (5/21) while taking vigabatrin and oxcarbazepine over 8 weeks. Ictal activity was suspected near the SEGA in the right frontal lobe; therefore, everolimus treatment was initiated to reduce the size of the SEGA. A confirmatory EEG was not feasible because of the severity of behaviors. Dose titration and serum level monitoring were conducted in accordance with FDA-approved guidelines [1,2]. Overall, data recorded during therapeutic serum levels of everolimus revealed a slight decrease in size of the SEGA (Fig. 1), decreased frequency of severe seizures, and improvement in facial angiofibromas. Severe seizures decreased to 8% (3/39) during 12 weeks of everolimus at therapeutic serum levels (5–15 ng/ml) and oxcarbazepine. After discontinuation of everolimus due to parental concern regarding an adverse event (pneumonia), frequency of severe seizures increased to 21% (6/29) over 8 weeks with oxcarbazepine alone. Other antiepileptic medication changes included weaning of vigabatrin and addition of rufinamide. These changes did not affect seizures, and rufinamide was discontinued after 2 weeks because of increased aggression and agitation.

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