PMID- 27815402
OWN - NLM
STAT- MEDLINE
DCOM- 20170512
LR  - 20220330
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 87
IP  - 23
DP  - 2016 Dec 6
TI  - Long-term treatment of epilepsy with everolimus in tuberous sclerosis.
PG  - 2408-2415
AB  - OBJECTIVE: To evaluate the long-term benefit and safety of everolimus for the 
      treatment of medically refractory epilepsy in patients with tuberous sclerosis 
      complex (TSC). METHODS: Everolimus was titrated over 4 weeks and continued an 
      additional 8 weeks in a prospective, open-label, phase I/II clinical trial 
      design. Participants demonstrating initial benefit continued treatment until 
      study completion (48 months). The primary endpoint was percentage of patients 
      with a >/=50% reduction in seizure frequency compared to baseline. Secondary 
      endpoints assessed absolute seizure frequency, adverse events (AEs), behavior, 
      and quality of life. RESULTS: Of the 20 participants who completed the initial 
      study phase, 18 continued extended treatment. Fourteen of 18 (78%) participants 
      completed the study, all but 1 of whom reported >/=50% reduction in seizure 
      frequency at 48 months. All participants reported at least 1 AE, the vast 
      majority (94%) of which were graded mild or moderate severity. Improvements in 
      behavior and quality of life were also observed, but failed to achieve 
      statistical significance at 48 months. CONCLUSIONS: Improved seizure control was 
      maintained for 4 years in the majority of patients with TSC with medically 
      refractory epilepsy treated with everolimus. Long-term treatment with everolimus 
      is safe and well-tolerated in this population. Everolimus may be a therapeutic 
      option for refractory epilepsy in TSC. CLASSIFICATION OF EVIDENCE: This study 
      provides Class IV evidence that for patients with TSC with medically refractory 
      epilepsy everolimus improves seizure control.
CI  - (c) 2016 American Academy of Neurology.
FAU - Krueger, Darcy A
AU  - Krueger DA
AD  - From the Departments of Pediatrics and Neurology (D.A.K., M.M., K.A., C.T., J.C., 
      K.H.-B., D.N.F.), University of Cincinnati College of Medicine; Division of Child 
      Neurology (D.A.K., M.M., K.A., C.T., J.C., K.H.-B., D.N.F.) and Pediatric 
      Neurology (A.A.W., C.M.T.), Texas Children's Hospital, Baylor College of 
      Medicine, Houston. krueger_darcy@cchmc.org.
FAU - Wilfong, Angus A
AU  - Wilfong AA
AD  - From the Departments of Pediatrics and Neurology (D.A.K., M.M., K.A., C.T., J.C., 
      K.H.-B., D.N.F.), University of Cincinnati College of Medicine; Division of Child 
      Neurology (D.A.K., M.M., K.A., C.T., J.C., K.H.-B., D.N.F.) and Pediatric 
      Neurology (A.A.W., C.M.T.), Texas Children's Hospital, Baylor College of 
      Medicine, Houston.
FAU - Mays, Maxwell
AU  - Mays M
AD  - From the Departments of Pediatrics and Neurology (D.A.K., M.M., K.A., C.T., J.C., 
      K.H.-B., D.N.F.), University of Cincinnati College of Medicine; Division of Child 
      Neurology (D.A.K., M.M., K.A., C.T., J.C., K.H.-B., D.N.F.) and Pediatric 
      Neurology (A.A.W., C.M.T.), Texas Children's Hospital, Baylor College of 
      Medicine, Houston.
FAU - Talley, Christina M
AU  - Talley CM
AD  - From the Departments of Pediatrics and Neurology (D.A.K., M.M., K.A., C.T., J.C., 
      K.H.-B., D.N.F.), University of Cincinnati College of Medicine; Division of Child 
      Neurology (D.A.K., M.M., K.A., C.T., J.C., K.H.-B., D.N.F.) and Pediatric 
      Neurology (A.A.W., C.M.T.), Texas Children's Hospital, Baylor College of 
      Medicine, Houston.
FAU - Agricola, Karen
AU  - Agricola K
AD  - From the Departments of Pediatrics and Neurology (D.A.K., M.M., K.A., C.T., J.C., 
      K.H.-B., D.N.F.), University of Cincinnati College of Medicine; Division of Child 
      Neurology (D.A.K., M.M., K.A., C.T., J.C., K.H.-B., D.N.F.) and Pediatric 
      Neurology (A.A.W., C.M.T.), Texas Children's Hospital, Baylor College of 
      Medicine, Houston.
FAU - Tudor, Cindy
AU  - Tudor C
AD  - From the Departments of Pediatrics and Neurology (D.A.K., M.M., K.A., C.T., J.C., 
      K.H.-B., D.N.F.), University of Cincinnati College of Medicine; Division of Child 
      Neurology (D.A.K., M.M., K.A., C.T., J.C., K.H.-B., D.N.F.) and Pediatric 
      Neurology (A.A.W., C.M.T.), Texas Children's Hospital, Baylor College of 
      Medicine, Houston.
FAU - Capal, Jamie
AU  - Capal J
AD  - From the Departments of Pediatrics and Neurology (D.A.K., M.M., K.A., C.T., J.C., 
      K.H.-B., D.N.F.), University of Cincinnati College of Medicine; Division of Child 
      Neurology (D.A.K., M.M., K.A., C.T., J.C., K.H.-B., D.N.F.) and Pediatric 
      Neurology (A.A.W., C.M.T.), Texas Children's Hospital, Baylor College of 
      Medicine, Houston.
FAU - Holland-Bouley, Katherine
AU  - Holland-Bouley K
AD  - From the Departments of Pediatrics and Neurology (D.A.K., M.M., K.A., C.T., J.C., 
      K.H.-B., D.N.F.), University of Cincinnati College of Medicine; Division of Child 
      Neurology (D.A.K., M.M., K.A., C.T., J.C., K.H.-B., D.N.F.) and Pediatric 
      Neurology (A.A.W., C.M.T.), Texas Children's Hospital, Baylor College of 
      Medicine, Houston.
FAU - Franz, David Neal
AU  - Franz DN
AD  - From the Departments of Pediatrics and Neurology (D.A.K., M.M., K.A., C.T., J.C., 
      K.H.-B., D.N.F.), University of Cincinnati College of Medicine; Division of Child 
      Neurology (D.A.K., M.M., K.A., C.T., J.C., K.H.-B., D.N.F.) and Pediatric 
      Neurology (A.A.W., C.M.T.), Texas Children's Hospital, Baylor College of 
      Medicine, Houston.
LA  - eng
GR  - P20 NS080199/NS/NINDS NIH HHS/United States
GR  - U01 NS082320/NS/NINDS NIH HHS/United States
GR  - U54 NS092090/NS/NINDS NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20161104
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Anticonvulsants)
RN  - 9HW64Q8G6G (Everolimus)
SB  - IM
MH  - Adolescent
MH  - Anticonvulsants/adverse effects/*therapeutic use
MH  - Child
MH  - Child, Preschool
MH  - Drug Resistant Epilepsy/*complications/*drug therapy
MH  - Everolimus/adverse effects/*therapeutic use
MH  - Female
MH  - Humans
MH  - Infant
MH  - Male
MH  - Seizures/complications/drug therapy
MH  - Time Factors
MH  - Treatment Outcome
MH  - Tuberous Sclerosis/*complications/*drug therapy
MH  - Young Adult
PMC - PMC5177677
EDAT- 2016/11/07 06:00
MHDA- 2017/05/13 06:00
PMCR- 2017/12/06
CRDT- 2016/11/06 06:00
PHST- 2016/04/15 00:00 [received]
PHST- 2016/09/06 00:00 [accepted]
PHST- 2016/11/07 06:00 [pubmed]
PHST- 2017/05/13 06:00 [medline]
PHST- 2016/11/06 06:00 [entrez]
PHST- 2017/12/06 00:00 [pmc-release]
AID - WNL.0000000000003400 [pii]
AID - NEUROLOGY2016738138 [pii]
AID - 10.1212/WNL.0000000000003400 [doi]
PST - ppublish
SO  - Neurology. 2016 Dec 6;87(23):2408-2415. doi: 10.1212/WNL.0000000000003400. Epub 
      2016 Nov 4.