Schiff N D, Giacino J T, Kalmar K, Victor J D, Baker K, Gerber M, Fritz B, Eisenberg B, Biondi T, O'Connor J, Kobylarz E J, Farris S, Machado A, McCagg C, Plum F, Fins J J, Rezai A R
Department of Neurology & Neuroscience, Weill Cornell Medical College, New York, New York 10021, USA.
Nature. 2007 Aug 2;448(7153):600-3. doi: 10.1038/nature06041.
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.
广泛的脑连接丧失被认为是严重创伤性脑损伤后支持交流和目标导向行为的脑机制失灵的基础。严重创伤性脑损伤后持续超过12个月的意识障碍通常被认为是不可改变的；在这种情况下，没有治疗方法被证明能加速恢复或改善功能结果。最近的研究表明，处于最小意识状态（MCS）的患者意外地保留了大规模脑网络，这种状态的特征是间歇性地出现自我或环境意识的证据。这些发现表明，一些患者可能存在残余功能能力，可通过治疗干预得到支持。我们假设，MCS中一些患者的进一步恢复受到潜在可招募的大规模网络长期激活不足的限制。在此，在一项为期6个月的双盲交替交叉研究中，我们表明，对丘脑中央核进行双侧深部脑电刺激（DBS）可调节一名在干预前因创伤性脑损伤而处于MCS状态6年的患者的行为反应性。与刺激关闭期相比，在刺激开启期，特定认知介导行为（主要结局指标）以及功能性肢体控制和经口进食（次要结局指标）的频率增加。逻辑回归模型显示，观察到的功能改善与近期刺激历史之间存在统计学关联。我们将DBS的作用解释为补偿完整大脑中通常由额叶控制的觉醒调节丧失。这些发现提供了证据，表明DBS可促进严重创伤性脑损伤后的显著晚期功能恢复。我们在损伤发生多年后的观察结果，对仅具有不一致交互行为的患者早期停止治疗的现有做法提出了挑战，并促使开展进一步研究以开发治疗干预措施。
