Behavioural improvements with thalamic stimulation after severe traumatic brain injury.
Widespread loss of cerebral connectivity is assumed to underlie the failure of brain mechanisms that support communication and goal-directed behaviour following severe traumatic brain injury. Disorders of consciousness that persist for longer than 12 months after severe traumatic brain injury are generally considered to be immutable; no treatment has been shown to accelerate recovery or improve functional outcome in such cases. Recent studies have shown unexpected preservation of large-scale cerebral networks in patients in the minimally conscious state (MCS), a condition that is characterized by intermittent evidence of awareness of self or the environment. These findings indicate that there might be residual functional capacity in some patients that could be supported by therapeutic interventions. We hypothesize that further recovery in some patients in the MCS is limited by chronic underactivation of potentially recruitable large-scale networks. Here, in a 6-month double-blind alternating crossover study, we show that bilateral deep brain electrical stimulation (DBS) of the central thalamus modulates behavioural responsiveness in a patient who remained in MCS for 6 yr following traumatic brain injury before the intervention. The frequency of specific cognitively mediated behaviours (primary outcome measures) and functional limb control and oral feeding (secondary outcome measures) increased during periods in which DBS was on as compared with periods in which it was off. Logistic regression modelling shows a statistical linkage between the observed functional improvements and recent stimulation history. We interpret the DBS effects as compensating for a loss of arousal regulation that is normally controlled by the frontal lobe in the intact brain. These findings provide evidence that DBS can promote significant late functional recovery from severe traumatic brain injury. Our observations, years after the injury occurred, challenge the existing practice of early treatment discontinuation for patients with only inconsistent interactive behaviours and motivate further research to develop therapeutic interventions.
Department of Neurology & Neuroscience, Weill Cornell Medical College, New York, New York 10021, USA. nds2001@mail.med.cornell.edu
N D
ND
Schiff
J T
JT
Giacino
K
K
Kalmar
J D
JD
Victor
K
K
Baker
M
M
Gerber
B
B
Fritz
B
B
Eisenberg
T
T
Biondi
J
J
O'Connor
E J
EJ
Kobylarz
S
S
Farris
A
A
Machado
C
C
McCagg
F
F
Plum
J J
JJ
Fins
A R
AR
Rezai
D000328:Adult; D001143:Arousal / Q000502:physiology; D001364:Awareness / Q000502:physiology; D001930:Brain Injuries / Q000503:physiopathology* / Q000534:rehabilitation / Q000628:therapy*; D046690:Deep Brain Stimulation; D004558:Electric Stimulation; D006801:Humans; D016015:Logistic Models; D008297:Male; D013060:Speech / Q000502:physiology; D013788:Thalamus / Q000502:physiology* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome