Recovery from vestibular dysfunction following Traumatic Brain Injury: A prospective behavioural and neuro-imaging study

创伤性脑损伤后前庭功能障碍的恢复：一项前瞻性行为和神经影像学研究

• 批准号: MR/P006493/1
• 负责人: Barry Seemungal
• 金额: $ 64.51万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FP006493%2F1
• 关键词: Recovery; vestibular; dysfunction; following; Traumatic

Traumatic Brain Injury (TBI) is the commonest cause of chronic disability in young adults. We found that 86% of acute TBI patients have problems with their balance. The problem of imbalance is important for this young working age group since previous studies have shown that following a mild TBI, at 6 months, 66% of TBI patients with balance problems will still be unemployed versus only 25% of those without balance dysfunction. A key step in treating TBI imbalance is to understand the underlying pathophysiology, however previous studies could not identify a clear-cut cause in 25% of TBI patients with chronic imbalance.Our acute TBI data show that most patients have a type of imbalance that is typical for patients with a loss of function of the inner ear balance organ - the vestibular organ. When we tested acute TBI patients with normal inner ear function we still found the same type of vestibular gait impairment, implying that the problem lay with the brain's processing of the vestibular organ's signals. Whilst screening acute TBI patients we also observed that acute TBI patients appeared to lose the perception of vertigo (the sensation of bodily self-motion) despite overt vestibular activation (vestibular nystagmus, nausea and vomiting). This again implies a failure by the brain to adequately process the inner ear vestibular signals. Taken together, TBI impairs the brain processing of vestibular signals with a major impact upon balance function. But what is the mechanism underlying this impairment of vestibular processing?Our previous work (Nigmatullina 2015) showed that vertigo perception is mediated by a cerebral cortical network. Congruent with this notion and using a test to quantify the vestibular perception of self-motion, we found that focal cortical damage from stroke did not affect vestibular perception of self-motion (Kaski 2015). In contrast, in our pilot data, we quantitatively show that acute TBI does indeed impair this vestibular perception of self-motion (which we call 'Vestibular Agnosia').We thus hypothesise that TBI causes a disruption of a cerebral cortical network that processes vestibular signals important for perceiving our sense of bodily motion. We additionally hypothesise that impairment of this vestibular cortical network will also compromise balance, particularly in the dark, since excessive sway (normally indicated by vestibular signals of head motion) will not be detected, leading to falls.Hence in our study we propose to:(i) prospectively assess if our vestibular perceptual test (of vestibular agnosia) predicts functional outcome;(ii) test our hypothesis that vestibular agnosia is a marker of brain network dysfunction; (iii) develop models linking pathophysiology and symptoms and hence enable us to explain why the persistence of symptoms post-TBI correlates poorly with TBI severity.The output of this study will thus enable us to:(i): predict which patients will be at risk of imbalance and falls post-TBI; (ii) objectively monitor the improvement in brain network dysfunction and hence provide an objective indicator of response to treatment;(iii) provide a clinical framework to progress the research and treatment of TBI including sports concussion.

创伤性脑损伤（TBI）是年轻人慢性残疾的最常见原因。我们发现86%的急性TBI患者存在平衡问题。对于这个年轻的工作年龄组来说，不平衡的问题很重要，因为以前的研究表明，在轻度TBI后，在6个月内，66%的TBI患者仍有平衡问题，而没有平衡功能障碍的患者只有25%。治疗TBI失衡的一个关键步骤是了解潜在的病理生理学，然而以前的研究无法确定25%的TBI患者慢性失衡的明确原因。我们的急性TBI数据显示，大多数患者有一种类型的失衡，这是内耳平衡器官-前庭器官功能丧失的典型患者。当我们测试内耳功能正常的急性TBI患者时，我们仍然发现了相同类型的前庭步态障碍，这意味着问题在于大脑对前庭器官信号的处理。在筛选急性TBI患者的同时，我们还观察到，尽管有明显的前庭激活（前庭眼球震颤、恶心和呕吐），但急性TBI患者似乎失去了眩晕感（身体自我运动的感觉）。这再次意味着大脑无法充分处理内耳前庭信号。总之，TBI损害前庭信号的大脑处理，对平衡功能产生重大影响。但是前庭处理功能受损的机制是什么呢？我们之前的工作（Nigmatullina 2015）表明眩晕感知是由大脑皮层网络介导的。与这一概念一致，并使用测试来量化前庭对自我运动的感知，我们发现中风引起的局灶性皮质损伤不会影响前庭对自我运动的感知（Kaski 2015）。相反，在我们的试验数据中，我们定量地表明急性TBI确实会损害前庭对自我运动的感知（我们称之为“前庭失认症”）。因此，我们假设TBI会导致大脑皮层网络的中断，该网络处理对感知我们的身体运动感很重要的前庭信号。我们还假设，前庭皮质网络的损伤也会损害平衡，特别是在黑暗中，因为过度的摇摆因此，在我们的研究中，我们建议：（i）前瞻性地评估我们的前庭知觉测试是否（2）验证我们的假设，即前庭失认症是大脑网络功能障碍的标志;（iii）建立病理生理学和症状的联系模型，从而使我们能够解释为什么TBI后症状的持续性与TBI的严重程度相关性很差。因此，本研究的结果将使我们能够：（i）预测哪些患者将处于TBI后失衡和福尔斯的风险中;（ii）客观地监测脑网络功能障碍的改善，从而提供对治疗反应的客观指标;（iii）提供临床架构，以推动创伤性脑损伤（包括运动性脑震荡）的研究和治疗。

项目成果

Predictors of clinical recovery from vestibular neuritis: a prospective study.

• DOI: 10.1002/acn3.386
• 发表时间: 2017-05
• 期刊: Annals of clinical and translational neurology
• 影响因子: 5.3
• 作者: Cousins S;Kaski D;Cutfield N;Arshad Q;Ahmad H;Gresty MA;Seemungal BM;Golding J;Bronstein AM
• 通讯作者: Bronstein AM

Vestibular agnosia in traumatic brain injury and its link to imbalance.

• DOI: 10.1093/brain/awaa386
• 发表时间: 2021-02-12
• 期刊: Brain : a journal of neurology
• 作者: Calzolari E;Chepisheva M;Smith RM;Mahmud M;Hellyer PJ;Tahtis V;Arshad Q;Jolly A;Wilson M;Rust H;Sharp DJ;Seemungal BM
• 通讯作者: Seemungal BM

Vestibular Deficits in Neurodegenerative Disorders: Balance, Dizziness, and Spatial Disorientation.

• DOI: 10.3389/fneur.2017.00538
• 发表时间: 2017
• 期刊: Frontiers in neurology
• 影响因子: 3.4
• 作者: Cronin T;Arshad Q;Seemungal BM
• 通讯作者: Seemungal BM

Downregulation of early visual cortex excitability mediates oscillopsia suppression.

• DOI: 10.1212/wnl.0000000000004360
• 发表时间: 2017-09-12
• 期刊: Neurology
• 影响因子: 9.9
• 作者: Ahmad H;Roberts RE;Patel M;Lobo R;Seemungal B;Arshad Q;Bronstein A
• 通讯作者: Bronstein A