usually several hundred milliseconds after stim-
ulation and are not strictly time locked to the
stimulus onset. Long-latency auditory cortical
potentials (N100, P150), the P300 response,
and the mismatch negativity (MMN) ERPs have
each shown some potential for providing evi-
dence of recovery. The P300 response can be
elicited by inclusion of an ‘‘oddball’’ tone in
an otherwise monotonous presentation of re-
peated identical tones. The MMN is an early
component of the auditory response to the
oddball stimulus that is attention independent
and reliably induced following the N100 au-
ditory cortex potential, an early primary audi-
tory evoked response. In a study of 346 patients
in coma for 12 months with outcomes divided
into VS versus all categories better than VS
(including MCS), N100 and MMN were strong
predictors of recovery past VS; no patient with
MMN in this cohort remained in VS. If the
electrophysiologic variables were combined
with information about the pupillary light re-
flex, the probability of recovery past VS
reached 89.9%.
40
However, other studies have
raised questions about the specificity of pre-
served ERP responses
75
in VS.
MINIMALLY CONSCIOUS STATE
The minimally conscious state
76
identifies a
condition of severely impaired consciousness
with minimal but definite behavioral evidence
of self or environmental awareness. Table 9–12
provides the criteria for the diagnosis of MCS.
Like VS, MCS often exists as a transitional state
arising during recovery from coma or during
the worsening of progressive neurologic dis-
ease. In some patients, however, it may be a
permanent condition. A few studies have ex-
amined differences in outcome between VS
and MCS. Giacino and Kalmar reported ret-
rospective findings in 55 VS patients and 49
MCS patients evaluated at 1, 3, 6, and 12
months following either traumatic or nontrau-
matic injuries.
77
Both presented with similar
levels of disability at 1 month postinjury. The
MCS patients, however, had significantly bet-
ter outcomes as measured by the Disability
Rating Scale compared with outcomes for VS
patients at 1 year, particularly in the TBI pa-
tients. Strauss and colleagues
78
retrospectively
studied life expectancy of a large number of
children (ages 3 to 15) in VS (N ¼ 564) and
MCS, dividing the latter into two groups:
immobile MCS (N ¼ 705) and mobile MCS
(3,806). A significant increase in the percent-
age of patients still alive at 8 years was noted
for the mobile MCS group (81%) compared to
theimmobileMCS(65%)ortheVS(63%)group;
the latter two were statistically indistinguish-
able. Lammi and associates
79
examined 18 MCS
patients 2 to 5 years after injury and found
a marked heterogeneity of outcome despite
prolonged duration of MCS after TBI. Most of
their patients regained functional indepen-
dence, but there was a poor correlation be-
tween duration of MCS and outcome. In gen-
eral, clinical and electrodiagnostic tests have
not yet been developed for use in the diagnosis
and prognosis of MCS outside of a research
context (see below for discussion).
MCS also includes some forms of the clini-
cal syndrome of akinetic mutism (Box 9–1) and
other less well-characterized disorders of con-
sciousness. At least two different identifiable
groups of patients are considered exemplars of
akinetic mutism. Although occasionally con-
fused with VS, classical akinetic mutism re-
sembles a state of constant hypervigilance. The
patients appear attentive and vigilant but
Table 9–12 Aspen Working Group
Criteria for the Clinical Diagnosis
of the Minimally Conscious State
Evidence of limited but clearly discernible self
or environmental awareness on a reproducible
or sustained basis, as demonstrated by one or
more of the following behaviors:
1. Simple command following
2. Gestural or verbal ‘‘yes/no’’ responses
(independent of accuracy)
3. Intelligible verbalization
4. Purposeful behavior including movements or
affective behaviors in contingent relation to
relevant stimuli. Examples include:
a. Appropriate smiling or crying to relevant
visual or linguistic stimuli
b. Response to linguistic content of questions
by vocalization or gesture
c. Reaching for objects in appropriate direction
and location
d. Touching or holding objects by
accommodating to size and shape
e. Sustained visual fixation or tracking as
response to moving stimuli
From Giacino et al.,
76
with permission.
360
Plum and Posner’s Diagnosis of Stupor and Coma
Box 9–1 Akinetic Mutism Versus ‘‘Slow Syndrome’’
The term akinetic mutism originated with Cairns and colleagues.
80
They described
a young woman who, although appearing wakeful, became mute and rigidly mo-
tionless when a craniopharyngiomatous cyst expanded to compress the walls of her
third ventricle and the posterior medial-ventral surface of the frontal lobe. The
patient appeared to be unconscious; there was no spasticity. After the cyst was
drained, she recovered full awareness but possessed no memory of the ‘‘uncon-
scious’’ period. Eye movements were not described in this woman but most doc-
umented cases of this type reveal seemingly attentive, conjugate eye movements.
Oculocephalic stimulation may elicit some lateral gaze.
Subsequent observations have shown that similar findings can be produced
by lesions of the medial-basal prefrontal area, the anterior cingulate cortex, the
medial prefrontal regions supplied by the anterior cerebral arteries, and the ros-
tral basal ganglia. A similar syndrome can rarely be a feature of untreated, rigid
Parkinson’s disease or prion disease.
81
The hyperattentive form of akinetic mutism is typically seen in patients with
bilateral lesions of the anterior cingulate and medial prefrontal cortices, as oc-
curs after rupture of an anterior communicating artery aneurysm.
82
The associated
injury may sometimes be accompanied by injury to the hypothalamus and anterior
pallidum. Castaigne and associates
83
and Segarra
84
introduced ‘‘akinetic mutism’’
to describe the behavior of patients suffering structural injuries affecting the
medial-dorsal thalamus extending into the mesencephalic tegmentum. The pa-
tients suffered severe memory loss and demonstrated apathetic behavior. Al-
though such patients exhibit severe global disturbances of consciousness, they
are not categorized as minimally conscious because they are capable of commu-
nication. To mitigate confusion, we use the term slow syndrome
85
to describe pa-
tients who appear apathetic and hypersomnolent but are able to move and may
speak with understandable words.
86
Unlike akinetic mute patients, they are not
semi-rigid and lack the appearance of vigilance. Subcortical lesions that may
produce the slow syndrome include bilateral lesions of the paramedian anterior or
posterior thalamus and basal forebrain; the mesencephalic reticular formation
including periaqueductal gray matter, caudate nuclei (or either caudate in isola-
tion), and globus pallidus interna; or selective interruption of the medial forebrain
bundle.
A common denominator of akinetic mute states may be damage to the cortico-
striato-pallidal-thalamocortical loops that are critical for the function of the frontal
lobes.
87
The prefrontal cortex is served by a loop including the ventral striatum,
ventral pallidum, and mediodorsal nucleus of the thalamus; akinetic mutism can
result from bilateral damage at any level of this system.
87
Similarly, bilateral injury
to the nigrostriatal bundle in the lateral hypothalamus may produce a state of
akinetic mutism that is reversible with dopaminergic agonists.
88
At least partial
cognitive function can be recovered following restricted bilateral injuries to the
paramedian thalamus and mesencephalon.
83,84,89,90
361