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Novel Brain Mapping Confirms Disruption of Ascending Arousal Network in Acute Traumatic Coma

Key findings

  • It's hypothesized that coma in patients with acute severe traumatic brain injury is caused by axonal injury within the ascending arousal network (AAn), but this has never been tested in humans in vivo
  • Massachusetts General Hospital researchers tested the hypothesis by using high-angular-resolution diffusion imaging to compare 16 comatose patients with 16 matched controls
  • Compared with controls, patients showed reduced connectivity in two of three AAn pathways: brainstem–hypothalamus and brainstem–thalamus
  • In contrast, only one of four subcortical pathways outside the AAn was reduced in patients compared with controls
  • The findings do not prove a causal relationship, but they support the role of AAn disruption in the pathogenesis of acute traumatic disorders of consciousness

Based on animal research and examination of human brain specimens, experts believe that coma in patients with acute severe traumatic brain injury (TBI) is caused by axonal injury within the ascending arousal network (AAn). The AAn is a set of subcortical pathways that connect the rostral brainstem tegmentum to the hypothalamus, thalamus and basal forebrain.

Until recently, this hypothesis couldn't be tested in vivo, because noninvasive tools have been unavailable to quantify the complex network of axonal connections. Now, using novel structural AAn mapping methods, researchers including Brian L. Edlow, MD, PhD, associate director of the Center for Neurotechnology and Neurorecovery at Massachusetts General Hospital, and Samuel B. Snider, MD, clinical fellow in the Department of Neurology, and colleagues have confirmed that TBI has pathophysiologic effects on the axonal architecture of the AAn. The data are reported in Neurology.

Study Methods

The research team prospectively enrolled 16 consecutive patients (median age 27.5 years, 12 men) who presented with acute traumatic coma to an ICU at Mass General. Inclusion criteria were age between 18 and 65 years, head trauma, no eye opening for 24 hours after injury and at least one neurologic examination before ICU admission in which a Glasgow Coma Scale score of 6 was assigned.

As soon as each patient was stable enough for transport, they underwent high-angular-resolution diffusion imaging (HARDI), which measures water diffusion along axonal pathways using a multidirectional model that's designed to detect crossing and branching axons. Sixteen age- and sex-matched controls underwent identical imaging.

In each subject, the researchers measured the connectivity probability of AAn axonal pathways linking the brainstem tegmentum to the hypothalamus, thalamus and basal forebrain.

Results

  • Compared with controls, patients showed reduced connectivity in two of three AAn pathways: brainstem–hypothalamus and brainstem–thalamus. The brainstem–forebrain pathway was relatively preserved
  • In contrast, only one of four subcortical pathways outside the AAn was reduced in patients compared with controls

Conclusion

These structural connectivity findings suggest a spatial specificity for AAn pathways among patients with a coma due to severe TBI. The findings do not prove a causal relationship, but they support the role of AAn disruption in the pathogenesis of acute traumatic disorders of consciousness.

Learn more about neurology research at Mass General

Refer a patient to the Department of Neurology

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The rate of misclassification of unconsciousness can be as high as 40%. A Mass General team studied using fMRI and EEG to better identify patients with unconsciousness in the ICU.

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Loss of consciousness associated with traumatic brain injury influences the risk of worse cognitive and somatic symptoms in the first few weeks after injury, but a history of a neurobehavioral condition has a larger role in determining whether symptoms will persist at three months.