The neuropathology of the vegetative state after an acute brain insult

Abstract

The vegetative state is often described clinically as loss of function of the cortex while the function of the brainstem is preserved. In an attempt to define the structural basis of the vegetative state we have undertaken a detailed neuropathological study of the brains of 49 patients who remained vegetative until death, 1 month to 8 years after an acute brain insult. Of these, 35 had sustained a blunt head injury and 14 some type of acute non-traumatic brain damage. In the traumatic cases the commonest structural abnormalities identified were grades 2 and 3 diffuse axonal injury (25 cases, 71%). The thalamus was abnormal in 28 cases (80%), and in 96% of the cases who survived for more than 3 months. Other abnormalities included ischaemic damage in the neocortex (13 cases, 37%) and intracranial haematoma (nine cases, 26%). In the non-traumatic cases there was diffuse ischaemic damage in the neocortex in nine cases (64%) and focal damage in four (29%); the thalamus was abnormal in every case. There were cases in both groups where the cerebral cortex, the cerebellum and the brainstem were of structurally normal appearance. In every case, however, there was profound damage to the subcortical white matter or to the major relay nuclei of the thalamus, or both. These lesions render any structurally intact cortex unable to function because connections between different cortical areas via the thalamic nuclei are no longer functional, and there is also extensive damage to afferent and efferent cerebral connections.

Structural consequences of diffuse traumatic brain injury: A large deformation tensor-based morphometry study

“…In fact, it is well-known that the mediodorsal nucleus and the pulvina are heavily connected to the prefrontal cortex (Goldman-Rakic & Porrino, 1985;Romanski, Giguere, Bates, & Goldman-Rakic, 1997), a key region in which TBI survivors frequently show structural and functional alterations. Our results also agree well with the post-mortem neuropathologic studies reporting thalamic damage in patients in a vegetative state after head injury (Adams, Graham, & Jennett, 2000;Graham, Maxwell, Adams, & Jennett, 2005;Kinney & Samuels, 1994). In particular, Graham and colleagues (2005) report that their patients had a greater amount of neuronal loss in mediodorsal nucleus, compared to more ventral or lateral parts of the thalamus.…”

Functional neuroanatomy of disorders of consciousness

“…This is supported by observations in transient unconscious states, such as during epileptic seizures, where the core pathology is related to the abnormality of brain function rather than macroscopic structure [17]. Nonetheless, widespread diffuse axonal injury and thalamic damage have been observed in patients with VS/UWS following traumatic brain injury [18,19], supporting the role of the thalamus and cerebral cortex in the genesis of awareness.…”

Synthetic consciousness: the distributed adaptive control perspective

“…Interestingly, enough this is fully consistent with the general circuit principle of TCD [110]: lack of medium spiny cell inhibition to the internal segment of the globus pallidus leads to hyperpolarization and pathological low-frequency bursting in thalamic cells, switching off the corresponding cortical circuit. The central role of the thalamus in the regulation of consciousness is further supported by the widespread thalamic neuronal cell death observed in vegetative state patients [111]. Another example, which illustrates the central role of the thalamo-cortical system as a core component of the neuronal substrate of consciousness, is that vasoconstriction of the middle cerebral artery, which provides blood to both cerebral cortex and the thalamus, can result in a transient loss of consciousness (syncope), associated with an increase of slow wave activity in the EEG indicative of functional inactivation of the cortex [112].…”