Handbook of Clinical Neurology, Vol.

90 (3rd series)
Disorders of consciousness
G.B. Young, E.F.M. Wijdicks, Editors
# 2008 Elsevier B.V. All rights reserved

Chapter 2

Consciousness: its neurological relevance

G. BRYAN YOUNG 1* AND EELCO F.M. WIJDICKS 2

1
London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada
2
Mayo Clinic College of Medicine, Rochester, MN, USA

We live in an exciting time for understanding con- functional organization and the fundamental impor-
sciousness and its disorders. Both basic science and tance of integration of various regions. Just as
clinical neurology provide insights into the under- improved technological approaches have shed light in
standing of how alertness and awareness arise in the basic neuroscience, functional neuroimaging and elec-
brain. trophysiology will give us more answers on a more
A recurring theme is that, although the functional macroscopic level for clinical neurology and related
anatomy of the brain is organized in a modular man- fields, e.g., neuropsychology (Vallar et al., 2003).
ner, for meaningful brain function there is a high The assessment of the unresponsive patient involves
degree of interaction among various regions. This examination, history-taking, and tailored investigative
includes feedback to sensory inputs that govern per- tests (Fig. 2.1). The objectives are to classify and anato-
ception and the focusing and selectivity of attentional mically localize the site of abnormality, to grade its
processes (Cudeiro and Sillito, 2006; Maunsell and severity, and to determine the etiology. Management,
Treue, 2006). The interaction of various seemingly including investigations, general supportive care, and
distinct functional areas, e.g., visual and auditory specific therapy is given in Chapter 20. Although the
systems, allows for integrated attention and also for approach to children shares many of these aspects, their
learning through plasticity (rewiring, new synapses, special aspects are covered in Chapter 19.
and strengthened circuits and connections) changes in The differential diagnosis of the unresponsive
the thalamus and cerebral cortex (Cudeiro and Sillito, state includes psychogenic unresponsiveness and the
2006). The key role of the hippocampus in acquir- locked-in syndrome. Psychogenic unresponsiveness is
ing new information is becoming better understood discussed in Chapter 18. In the locked-in syndrome
(Delgado-Garcia and Gruart, 2006). Just how conscious the patient is awake and aware but cannot move the
awareness arises from this integrated brain activity is limbs, the lower bulbar musculature, or lower facial
still unclear but the processes that are involved are muscles. The orbicularis oculi and vertical and conver-
better understood. Powerful new neurobiological tech- gent eye movements are preserved. This constellation
nologies in basic neuroscience hold promise for the of clinical features is due to a lesion in the basis pon-
detailed neurophysiology of various components of tis, either due to ischemia in the basilar artery territory
consciousness, especially processing of and combin- or another structural lesion, such as central pontine
ing of information and the initiation of responses. myelinolysis. It can be determined that the patient is
Dr Zeman provides a masterly discussion of conscious- conscious by having the patient visually track a target
ness from a neurological perspective in Chapter 1. moving in the vertical plane or open and close the
Clinical insights based on the jacksonian approach eyes to command. A more complete locked-in syn-
of studying excitatory and destructive phenomena in drome may be caused by generalized neuromuscular
the brain (as discussed in Chs. 10 and 13) also provide paralysis that may sometimes occur with a severe
us with similar insights and respect for the brain’s polyneuropathy or by sustained action of neuromuscu-

*
Correspondence to: Dr G.B. Young, Professor of Neurology, Department of Clinical Neurological Sciences, University Hospital,
London Health Sciences Centre, 339 Windermere Rd, University of Western Ontario, London, Ontario, Canada N6A 5A5.
E-mail: bryan.young@lhsc.on.ca, Tel: þ1-519-663-2911, Fax: þ1-519-663-3753.
34 G.B. YOUNG AND E.F.M. WIJDICKS
“Unresponsive”

Yes
Aphasic
No Locked-in (central-peripheral)
Comatose
Psychogenic unresponsiveness
Catatonic
Yes
Laboratory studies for
No metabolic-toxic-inflammatory-
infectious causes Specific
Structural cause likely
CSF therapy
EEG
Yes

No No
Intrinsic brain stem Intrinsic hemispheres Extra axial

Yes Yes Yes

Consider specific medical or surgical options

Yes
No
Improvement
Im Discuss level of care

Fig. 2.1. Assessment of the unresponsive patient.

lar blocking agents. Proof of consciousness, especially space or personal body space, and constitute a
with Guillain–Barré syndrome, can be obtained restricted or focal type of diminished consciousness.
through an EEG recording, which should show normal Neglect syndromes can occur dissociated from any
awake rhythms, e.g., the alpha rhythm that blocks problems with sensory pathways or primary sensory
with passive eye opening and reappears with eye areas. The main sites of abnormality are in the het-
closure. eromodal cortices of the parietal (especially in the
Impairment of alertness implies dysfunction of the right or nondominant hemisphere) or frontal lobes.
ascending reticular activating system (ARAS): cere- They thus represent a defect in higher order proces-
bral hemispheres (cerebral cortex, thalamus, or inter- sing and are commonly accompanied by extinction
vening white matter) and rostral brainstem. Acute (the loss of awareness of one of two simultaneously
dysfunction of the dominant hemisphere alone can competing stimuli) and perseverative activity (Ciçek
sometimes produce a transient impairment of alertness et al., 2007).
(Salazar et al., 1986). 2. Delirium (Ch. 3) consists of impairment in the abil-
Awareness, the ‘content of consciousness’, requires ity to maintain attention, along with various asso-
integrated function of the cerebral cortex and thalamus. ciated features, e.g., disturbance in the sleep–wake
Impairments in various aspects of awareness (including cycle, changes in psychomotor activity (increased
perception, apperception, declarative memory, working or decreased), disorientation, and altered percep-
memory, cognition, and planned activity) result from tions. Delirium, or confusion, reflects a generalized
structural or metabolic disturbances of these regions. disturbance in integrated brain function, but regions
that have been incriminated either singly or with
other regions include the anterior cingulate region,
2.1. Classification
the prefrontal cortex, and parietal regions as well
as subcortical nuclei in the thalamus and rostral mid-
Impairment of consciousness can be classified into a
brain tegmentum.
number of syndromes:
3. The vegetative state (Ch. 6) refers to wakefulness
1. Neglect syndromes are best characterized as unilat- without the capacity for awareness. Anatomically,
eral loss of awareness of contralateral extrapersonal the sites of involvement are either the cerebral cor-
 CONSCIOUSNESS: ITS NEUROLOGICAL RELEVANCE 35
tex bilaterally, the thalamus, or the intervening meningitis or neurological complications of systemic
white matter that interconnects various cortical infection (see Ch. 11). Previous valvular heart disease
areas or the cortex to the thalamus. raises the possibility of endocarditis or multiple cerebral
4. The minimally conscious state (Ch. 6) consists of emboli. A background of cancer could indicate meta-
some interaction with the environment, such as stases, side effects of drugs, or ‘remote effects’ on
tracking with the eyes (akinetic mutism) or limited the nervous system (see Ch. 15). Medications should be
responses, but the patient’s integrated brain func- listed and a search should be undertaken for any per-
tion is grossly impaired. The patient is dependent sonal information, such as a Medical Alert bracelet or
and does not initiate anything other than basic a suicide note.
homeostatic activity.
5. Stupor and coma (Ch. 4). Stupor is a state of
2.2.2. The neurological examination
impaired alertness in which the patient can briefly
be aroused to eye opening and some responsive-
The chief value of the neurological examination is to
ness. The patient goes back to an eyes-closed, non-
assess the level of consciousness (see above), assess-
interactive state when the stimulation ceases. Coma
ment of cranial nerve functions, motor responses, and
is unarousable unconsciousness and implies dys-
respirations. Funduscopy should form a part of the
function of the ARAS.
assessment routine. The presence of papilledema indi-
6. Brain death is the total and irreversible loss of brain
cates raised intracranial pressure. A subhyaloid (pre-
function. Clinical ‘brain death criteria’ for most
retinal) hemorrhage is almost always associated with
countries are met if the entire extent of the brainstem
an acute intracerebral hemorrhage, especially a rup-
and the hypothalamus are irreversibly destroyed.
tured berry aneurysm. Among cranial nerve reflexes,
Ancillary testing, however, must show loss of total
pupillary, corneal, vestibulo-ocular, pharyngeal, and
brain function, as revealed by tests revealing
cough reflexes are routinely examined. Most metabolic
absence of blood flow to the entire brain.
disorders spare the pupillary light reflex, although
some drugs may affect pupillary size and/or reactions
2.2. Etiology symmetrically. For example, opiates and organic phos-
phates cause small, reactive pupils, while intact pupillary
After defining the category and thus the approximate reflexes indicate the optic nerves and the rostral brain
site of impairment of consciousness (above), clues as stem are functioning and are unlikely to be involved
to the etiology should be sought. in a structural cause for coma. The vestibular–ocular
reflex (VOR) can be used to assess eye movements
2.2.1. History in the horizontal and vertical planes. Caloric (usually
ice-water) testing is more potent than oculocephalic
This usually has to be obtained from family members, reflex testing, by moving the head, and is safer in
friends, or other witnesses who have been with the the face of possible neck injury or instability of the cer-
patient or who have witnessed a collapse. The time vical spine. A large part of the brainstem tegmentum
course is helpful. A sudden collapse favors a cata- (from medulla to midbrain) as well as the IIIrd and VIth
strophic cause such as an intracranial hemorrhage or cranial nerves are assessed with this testing. It should be
loss of general circulation. A fluctuation in impairment remembered that the VOR can be selectively affected
suggests a metabolic or toxic cause (see Chs. 7–9 and without impairment of the pupillary light reflex in
11), or occasionally an extra-axial lesion, e.g., a sub- Wernicke’s encephalopathy and in sedative drug
dural hematoma or raised intracranial pressure. Inter- intoxication (unpublished observations). Spontaneous
mittent discrete attacks occur in seizure disorders, eye movements are also worth noting. Nystagmus
syncope, recurrent hypoglycemia or, uncommonly, retractorius and convergence nystagmus are due to dif-
focal ischemia or ventricular obstruction. A gradual fuse excitation of the IIIrd nerve complex in the mid-
impairment in consciousness after preceding neurolo- brain and often indicate a structural lesion in this
gical symptoms could indicate a progressively increas- region or an underlying seizure discharge (we have
ing mass lesion with ultimate herniation (see Ch. 5). observed this in association with hyperglycemic coma
A history of depression, anxiety, or substance abuse and seizures). Ocular bobbing is a rapid downward
raises other possibilities, including self-intoxication. movement of both eyes together followed by their
A history of underlying chronic or preceding ill- slow return to the horizontal plane. It often indicates
nesses or symptoms may be helpful. A recent fever sug- a lesion or dysfunction in the caudal pons. Its obverse,
gests an infectious process, e.g., an encephalitis or ocular dipping (slow downward followed by rapid
36 G.B. YOUNG AND E.F.M. WIJDICKS
upward conjugate eye movements) also indicates barbiturate intoxication. Needle tracks suggest drug
pontine dysfunction but is most common in anoxic– abuse or complications thereof. Hyperpigmentation of
ischemic encephalopathy. Palatal and pharyngeal the skin or mucous membranes suggest Addison’s dis-
reflexes involve brainstem regions caudal to those ease. Myxedema coma is suggested by periorbital
key structures responsible for consciousness and are edema, a large tongue and pale, doughy, cool skin.
useful for localization purposes and in the clinical The breath can suggest alcohol or cyanide intoxica-
assessment of brain death. tion, liver or renal failure, or diabetic ketoacidosis.
Cardiac murmurs raise the possibility of cardiac
2.2.3. The general examination embolism. The abdominal examination may reveal
signs of liver disease or large kidneys in polycystic
Vital signs can provide key clues. Markedly elevated kidney disease (and subarachnoid hemorrhage from a
blood pressure could indicate hypertensive encephalo- ruptured berry aneurysm).
pathy (almost always associated with papilledema) or Signs of meningeal irritation, as found in meningi-
the posterior reversible leukoencephalopathy syndrome tis or subarachnoid hemorrhage, may be absent in
(PRES). Otherwise hypertension may be secondary to coma but are helpful when found and include: 1) resis-
the intracranial process, e.g., stroke, raised intracranial tance to neck flexion; 2) pain on straight leg raising
pressure. Severe hypotension (shock), of course, sug- (Kernig’s sign) or flexion of the contralateral lower
gests global hypoperfusion but also indicates a serious limb when one hip is flexed (Brudzinki’s sign).
underlying condition, e.g., sepsis, hemorrhage, etc. This volume should help us think in an anatomical
Hypothermia could be symptomatic of hypothyroidism, and physiological manner as we attempt to understand
environmental cold exposure, intoxication, hypothala- the effects of various disorders affecting the brain at dif-
mic dysfunction (as in Wernicke’s encephalopathy), ferent times of life. While neurologists are clinical
or even severe systemic infection. Hyperthermia scientists, they are also doctors who are aware of their
usually suggests central nervous system or systemic patients and families as fellow humans. These indivi-
infection but acute adrenal failure, cocaine intoxication, dual and collective aspects, along with the various ethi-
brainstem stroke, malignant hyperthermia, or neurolep- cal and legal implications of their work, are factored
tic malignant syndrome are other possibilities. management decisions involving patients with the life-
Trauma is suggested by bruising (especially if lin- threatening illnesses discussed in this book (see Ch. 21).
ear) or lacerations but specific signs of head injury,
especially basal skull fracture, include unilateral or References
bilateral periorbital ecchymoses (raccoon eyes) with
extension to but not beyond the orbital ridges with Ciçek M, Gitelman D, Hurley RS et al. (2007). Anatomical
orbital roof fractures, Battle’s sign (bruising over the physiology of spatial extinction. Cereb Cortex 17:
mastoid), or hemotympanium – both suggestive of a 2892–2898.
fracture through the petrous temporal bone. A bitten Cudeiro J, Sillito AM (2006). Looking back: corticothalamic
tongue or posterior fracture-dislocation of the humerus feedback and early visual processing. Trends Neurosci 29:
is suggestive of an earlier convulsive seizure. 298–306.
Examination of the skin can reveal helpful informa- Delgado-Garcia JM, Gruart A (2006). Building new motor
tion. Hepatic coma is suggested by jaundice or other responses: eyelid conditioning revisited. Trends Neurosci
29: 330–338.
stigmata of liver disease. Cherry red discoloration of
Maunsell JHR, Treue S (2006). Feature-based attention in
the lips, mucous membranes, or skin implies carbon visual cortex. Trends Neurosci 29: 317–322.
monoxide intoxication. Petechiae or purpura raise the Salazar AM, Grafman JH, Vance SC et al. (1986). Conscious-
possibility of meningococcemia, thrombotic thrombo- ness and amnesia after penetrating head injury: neurology
cytopenic purpura, disseminated intravascular coagula- and anatomy. Neurology 36: 178–187.
tion, or Rocky Mountain spotted fever. Bullous Vallar G, Bottini G, Paulesu E (2003). Neglect syndromes:
skin lesions, ‘coma blisters’, are seen in massive the role of the parietal cortex. Adv Neurol 93: 293–319.