PMID- 25748452
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20191210
IS  - 1552-6844 (Electronic)
IS  - 1545-9683 (Linking)
VI  - 30
IP  - 2
DP  - 2016 Feb
TI  - Epidural Electrical Stimulation for Stroke Rehabilitation: Results of the 
      Prospective, Multicenter, Randomized, Single-Blinded Everest Trial.
PG  - 107-19
LID - 10.1177/1545968315575613 [doi]
AB  - BACKGROUND: This prospective, single-blinded, multicenter study assessed the 
      safety and efficacy of electrical epidural motor cortex stimulation (EECS) in 
      improving upper limb motor function of ischemic stroke patients with moderate to 
      moderately severe hemiparesis. METHODS: Patients >/= 4 months poststroke were 
      randomized 2:1 to an investigational (n = 104) or control (n = 60) group, 
      respectively. Investigational patients were implanted (n = 94) with an epidural 
      6-contact lead perpendicular to the primary motor cortex and a pulse generator. 
      Both groups underwent 6 weeks of rehabilitation, but EECS was delivered to 
      investigational patients during rehabilitation. The primary efficacy endpoint 
      (PE) was defined as attaining a minimum improvement of 4.5 points in the upper 
      extremity Fugl-Meyer (UEFM) scale as well as 0.21 points in the Arm Motor Ability 
      Test (AMAT) 4 weeks postrehabilitation. Follow-up assessments were performed 1, 
      4, 12, and 24 weeks postrehabilitation. Safety was evaluated by monitoring 
      adverse events (AEs) that occurred between enrollment and the end of 
      rehabilitation. RESULTS: Primary intent-to-treat analysis showed no group 
      differences at 4 weeks, with PE being met by 32% and 29% of investigational and 
      control patients, respectively (P = .36). Repeated-measures secondary analyses 
      revealed no significant treatment group differences in mean UEFM or AMAT scores. 
      However, post hoc comparisons showed that a greater proportion of investigational 
      (39%) than control (15%) patients maintained or achieved PE (P = .003) at 24 
      weeks postrehabilitation. Investigational group mean AMAT scores also improved 
      significantly (P < .05) when compared to the control group at 24 weeks 
      postrehabilitation. Post hoc analyses also showed that 69% (n = 9/13) of the 
      investigational patients who elicited movement thresholds during stimulation 
      testing met PE at 4 weeks, and mean UEFM and AMAT scores was also significantly 
      higher (P < .05) in this subgroup at the 4-, 12-, and 24-week assessments when 
      compared to the control group. Headache (19%), pain (13%), swelling (7%), and 
      infection (7%) were the most commonly observed implant procedure-related AEs. 
      Overall, there were 11 serious AEs in 9 investigational group patients (7 
      procedure related, 4 anesthesia related). CONCLUSIONS: The primary analysis 
      pertaining to efficacy of EECS during upper limb motor rehabilitation in chronic 
      stroke patients was negative at 4 weeks postrehabilitation. A better treatment 
      response was observed in a subset of patients eliciting stimulation induced upper 
      limb movements during motor threshold assessments performed prior to each 
      rehabilitation session. Post hoc comparisons indicated treatment effect 
      differences at 24 weeks, with the control group showing significant decline in 
      the combined primary outcome measure relative to the investigational group. These 
      results have the potential to inform future chronic stroke rehabilitation trial 
      design.
CI  - (c) The Author(s) 2015.
FAU - Levy, Robert M
AU  - Levy RM
AD  - Marcus Neuroscience Institute, Boca Raton, FL, USA.
FAU - Harvey, Richard L
AU  - Harvey RL
AD  - Northwestern University Feinberg School of Medicine, Chicago, IL, USA The 
      Rehabilitation Institute of Chicago, Chicago, IL, USA rharvey@ric.org.
FAU - Kissela, Brett M
AU  - Kissela BM
AD  - University of Cincinnati, Cincinnati, OH, USA.
FAU - Winstein, Carolee J
AU  - Winstein CJ
AD  - University of Southern California, Los Angeles, CA, USA.
FAU - Lutsep, Helmi L
AU  - Lutsep HL
AD  - Oregon Health & Science University, Portland, OR, USA.
FAU - Parrish, Todd B
AU  - Parrish TB
AD  - Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
FAU - Cramer, Steven C
AU  - Cramer SC
AD  - University of California, Irvine, CA, USA.
FAU - Venkatesan, Lalit
AU  - Venkatesan L
AD  - St. Jude Medical, Plano, TX, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00170716
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150306
PL  - United States
TA  - Neurorehabil Neural Repair
JT  - Neurorehabilitation and neural repair
JID - 100892086
SB  - IM
MH  - Adult
MH  - Aged
MH  - Electric Stimulation Therapy/adverse effects/*methods
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Motor Cortex/*physiopathology
MH  - *Outcome Assessment, Health Care
MH  - Prospective Studies
MH  - Single-Blind Method
MH  - *Stroke Rehabilitation
OTO - NOTNLM
OT  - cortical stimulation
OT  - hemiparesis
OT  - rehabilitation
OT  - stroke
EDAT- 2015/03/10 06:00
MHDA- 2016/12/15 06:00
CRDT- 2015/03/10 06:00
PHST- 2015/03/10 06:00 [entrez]
PHST- 2015/03/10 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - 1545968315575613 [pii]
AID - 10.1177/1545968315575613 [doi]
PST - ppublish
SO  - Neurorehabil Neural Repair. 2016 Feb;30(2):107-19. doi: 10.1177/1545968315575613. 
      Epub 2015 Mar 6.