**Neuroimaging and Outcome Assessment in Vegetative and Minimally Conscious State**

Silvia Marino, Rosella Ciurleo, Annalisa Baglieri, Francesco Corallo, Rosaria De Luca, Simona De Salvo, Silvia Guerrera, Francesca Timpano, Placido Bramanti and Nicola De Stefano

*IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Dept. of Neurology, Neurosurgery & Behavioral Sciences, University of Siena, Siena, Italy* 

#### **1. Introduction**

180 Neuroimaging – Cognitive and Clinical Neuroscience

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and late-night sleep with functional brain states promoting insight to abstract task regularity, *PLoS One*, 5(2):e9442. http://dx.plos.org/10.1371/journal.pone.0009442

http://dx.plos.org/10.1371/journal.pone.0005675

Consciousness is a multifaceted concept that has two dimensions: arousal, or wakefulness (i.e., level of consciousness), and awareness (i.e., content of consciousness) (Laureys et al., 2004). An accurate and reliable assessment of the arousal and awareness of consciousness in patients with severe brain damage is of greatest importance for the differential diagnosis of low levels consciousness patients and for outcome evaluation. Following coma, some patients permanently lose all brainstem function (brain death), some progress to "wakeful unawareness" (vegetative state - VS), whereas others recover typically and progress through different stages before fully or partly recovering consciousness (minimally conscious state - MCS). Patients in VS can open their eyes and exhibit basic orienting responses, but show no conscious, purposeful activity. Reflex and other movements are seen, mediated by brainstem, spinal cord, and brainstem-diencephalic arousal systems (Laureys et al., 2004). VS can occur after patients emerge from an acute catastrophic brain insult causing coma, or can also be seen in degenerative or congenital nervous system disorders. The two common findings are necrosis of the cerebral cortex, thalamus and brainstem (usually after anoxic injury) and diffuse axonal injury (usually after trauma), although other pathological findings can be seen in degenerative and other disorders (Laureys, 2008). The MCS patients do not meet diagnostic criteria for coma or VS because they demonstrate some inconsistent but clear evidence of consciousness (Laureys et al., 2008; Giacino et al., 2002). In the MCS, there is variable impaired function of the cerebral cortex, diencephalons and upper brainstem. This allows occasional conscious behaviours to occur, unlike in VS or coma. Patients may enter the MCS as they emerge from coma or VS, or they can become minimally conscious as a result of acute injury or chronic degenerative diseases. Recent studies suggest a number of potential clinical and rehabilitative applications of magnetic resonance (MR) techniques. Although bedside clinical examination remains the criterion standard for establishing diagnosis, MR may provide an adjunctive diagnostic role when behavioural findings are very limited or ambiguous. The future of diagnostic and prognostic assessment of patients with disorders of consciousness (DOC) envisions a battery of neurobehavioral and neuroimaging techniques (such as structural and functional MR imaging (MRI and

Neuroimaging and Outcome Assessment in Vegetative and Minimally Conscious State 183

outcomes of the patients was found. All patients in the most unfavorable class III clinical outcome group (i.e. persistent VS) exhibited white matter lesions exceeding 2/3 of the

Moreover, Juengling et al. (2005) investigated 5 patients in persistent VS due to prolonged cerebral hypoxia of non-traumatic origin, using combined Voxel-Based Morphometry (VBM) of 3D MRI and FDG-PET analysis. In the analysis of the regional distribution of gray matter atrophy, VBM revealed multiple areas of significantly decreased gray matter density at p<.001, corrected for multiple comparisons. Those were localized in multiple cortical areas, in particular including inferior parietal lobe, superior and medial frontal lobe, paracentral lobule, superior and medial temporal lobe, the cingulum, and the fusiform gyrus. Thalamic changes were limited to small voxel clusters in dorso-medial areas. These structural atrophic changes were compared with the local distribution of functional loss as assessed by regional hypometabolism in the FDG-PET group analysis. At the threshold pb0.001 (corrected for multiple comparisons), PET showed a widespread pattern of hypometabolic areas. In particular, the parietal and frontotemporal cortices, the cuneus/precuneus, the cingulum, the frontal medial and precentral gyrus, and the transverse temporal gyrus were involved, additionally the bilateral thalamus (mainly dorsomedial subnucleus). All changes were, similar to the VBM results, nearly symmetrical. Improved understanding of this complex lesion pattern gained by in vivo group analyses like here might help to provide deeper insights into the general pathoanatomy of patients in

Using high-resolution T1-weighted magnetic resonance images and a novel approach to shape analysis applied SIENAX software, Fernandez-Espejo et al. (2010) investigated thalamic global and regional changes in a sample of patients in a VS or an MCS. They found that total thalamic volume was significantly lower in patients than in healthy volunteers. Shape analysis revealed significant bilateral regional atrophy in the dorso-medial body in patients compared to controls; this atrophy was more widespread in VS than in MCS patients. Lower thalamic volume was significantly correlated with worsening of Disability Rating Scale (DRS) scores. Shape analysis suggested that the dorso-medial nucleus and the internal medullar lamina were the main regions responsible for this correlation. These findings suggest that MCS and VS patients present different patterns of regional thalamic abnormalities. In particular, VS patients showed a more widespread pattern of atrophy than controls, producing differences in global thalamic volume. MCS patients did not show volumetric differences compared to controls, and regionally they showed a less pronounced inward collapse in both the dorsal and ventral areas, with the anterior-ventral body significantly spared. Neuropathological studies have demonstrated that thalamic damage is

Another quantitative RM technique is the Magnetization Transfer Imaging (MTI). The MTI relies on the principle that protons bound in structures exhibit T1 relaxation coupling with protons in the aqueous phase. When an off-resonance saturation pulse is applied, it selectively saturates those protons that are bound in macromolecules. These protons subsequently exchange longitudinal magnetization with free water protons, leading to a reduction in the detected signal intensity (Sinson et al., 2001). The MTI may provide a quantitative index of the structural integrity of tissue and might be useful to study the

However, further studies, on larger groups of patients, need to be performed to confirm the usefulness of quantitative MRI in the assessment of the eventual neurological prognosis and

volume of at least one lobe, most frequently the occipital lobe.

less common in MCS than in VS patients (Jennett et al., 2001).

outcome of patients with low levels of consciousness.

outcome of these challenging patients.

the persistent VS.

fMRI), MR spectroscopy (MRS), diffusion tensor imaging (DTI), fiber tracking, positron emission tomography (PET)) that serve as complementary clinical tools that may help differentiate the effects of underarousal, sensory impairment, motor dysfunction, and cognitive disturbance in the search for potential causes of behavioural unresponsiveness.
