Neurological education
J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2015-312193 on 17 February 2016. Downloaded from http://jnnp.bmj.com/ on 27 November 2018 by guest. Protected by
1
The Neurorehab Clinic,
London, UK
2
The London Independent
Hospital, London, UK
3
Barts and The London School
of Medicine and Dentistry,
QMUL at the Royal London
Hospital, London, UK
4 for surgery, and the development of acute or post-
Institute of Neuroscience,
University of Lisbon, Lisbon,
Portugal
Correspondence to
Daniel Friedland, The
Neurorehab Clinic, P.P.C.S., 14
Devonshire Place, London UK;
danielfriedland@hotmail.com
Received 4 September 2015
Revised 20 January 2016
Accepted 29 January 2016
Published Online First
17 February 2016
To cite: Friedland D,
Swash M. J Neurol
Neurosurg Psychiatry
2016;87:1068–1074.
1068
REVIEW
Post-traumatic amnesia and confusional state:
hazards of retrospective assessment
Daniel Friedland,1 Michael Swash2,3,4
ABSTRACT
Retrospective assessment of post-traumatic amnesia
(PTA) must take into account factors other than
traumatic brain injury (TBI) which may impact on
memory both at the time of injury and subsequent to
the injury. These include analgesics, anaesthesia required
traumatic stress disorder. This is relevant in clinical and
medicolegal settings. Repeated assessments of the post-
injury state, involving tests for continuing amnesia, risk
promoting recall of events suggested by the examiner, or
generating confabulations. The PTA syndrome affects the
categorical autobiographical memory, and is
accompanied by confusion as an essential component;
this should be suspected from the initial or early
Glasgow Coma Scale score (13–14/15) if not directly
recorded by clinical staff. PTA by itself is only one of
several indices of severity of TBI. The nature of the head
injury, including observers’ accounts, clinical and
neuroimaging data, the possible role of other external
injuries, blood loss, acute stress disorder and the
potential for hypoxic brain injury, must be taken into
account as well as concomitant alcohol or substance
abuse, and systemic shock. A plausible mechanism for a
TBI must be demonstrable, and other causes of amnesia
excluded.
INTRODUCTION
Retrospective assessment of the duration of post-
traumatic amnesia (PTA) is generally considered a
reasonably robust measure of severity of traumatic
brain injury (TBI), especially in medicolegal prac-
tice. Indeed, PTA is often taken as the principal
index of severity of TBI, without attention to other
relevant phenomena. It is classically associated with
a confusional state, although this may not be imme-
diately obvious to the casual observer. In the clin-
ical context, assessment often takes place months
or years after brain injury, and the assessment is not
necessarily reliable or consistent. In this review, we
consider retrospective clinical assessment of PTA,
especially the manner in which it is tested, its inter-
pretation and its relationship to other indices of
TBI in the context of the time elapsed after injury.
In particular, we stress that multifaceted compara-
tive quantitative studies of memory in people with
TBI in the acute and later stages of recovery are
lacking. We discuss reasons for caution in relying
on the phenomenon of PTA to the exclusion of
other information. We argue that PTA may not be
reliable and that it is not linearly graded in relation
to severity of brain injury as judged, most rele-
vantly, by outcome. In this review, we focus
Friedland D, Swash M. J Neurol Neurosurg Psychiatry 2016;87:1068–1074. doi:10.1136/jnnp-2015-312193
especially on mild TBI (box 1), since this poses the
most difficult problems in assessment.1
THE SENSITIVITY OF PTA AS AN INDEX OF TBI
SEVERITY
TBI is defined as an alteration in brain function, or
other evidence of brain pathology, caused by an
external force.1 2 This therefore includes loss of
consciousness or a decreased level of consciousness,
other neurological and neuropsychological features,
and abnormalities on investigation, especially neu-
roimaging.3 The concept of an acute post-traumatic
alteration in brain function includes a confusional
state, often revealed by a reduced Glasgow Coma
Scale (GCS) score (14/15), with loss of memory for
events after the injury (PTA) or, rather less promin-
ently, immediately before the injury (retrograde
amnesia). PTA has assumed particular importance
in the medicolegal assessment after TBI, since it has
become widely accepted as an objective and reliable
measure, even when assessed long after the injury.4
copyright.
However, there are problems in accepting this
retrospective approach to PTA, especially in mild
or minor TBI.
VALIDITY OF PTA ASSESSMENT
In medicolegal practice involving TBI, PTA is
almost invariably assessed retrospectively, often
several years after the injury. As background to this
assessment, much depends on the quality of the
contemporaneous medical records. There is usually
some information about the accident itself, and the
GCS is almost universally available from assessment
at the scene both at the scene and in the accident
and emergency department at the hospital; the
GCS is a validated, ordinal, multidimensional
measure of brain function that is equated to the
level of consciousness, but in practice the PTA is
only rarely prospectively assessed in this setting.
The retrospective analysis of PTA therefore assumes
particular importance in assessing the severity of
the TBI,5 and other aspects of the post head injury
state tend to be neglected. The validity of such a
retrospective assessment of PTA, perhaps made
several years after the injury, is controversial. King
et al6 commented on a significant misclassification
rate, suggesting that reliance on PTA alone was haz-
ardous, particularly at the milder end of the TBI
spectrum. Nonetheless, it can be particularly
important to assess PTA retrospectively in a patient
with a previous mild TBI, even when, at the time
of the injury, no confusional state was apparent.7
When the person has no recollection of the acci-
dent, retrospective assessment of PTA is the only

Box 1 WHO definition of mild traumatic brain injury
(MTBI)1
MTBI is an acute brain injury resulting from mechanical energy
to the head from external force. Operational criteria for clinical
identification include
1. One or more of the following: confusion or disorientation,
loss of consciousness for 30 min or less, post-traumatic
amnesia for <24 h, and/or other transient neurological
abnormalities such as focal signs, seizure, and intracranial
lesion not requiring surgery
2. Glasgow Coma Scale score of 13–15 after 30 min post head
injury or later on presentation for healthcare. These
manifestations of MTBI must not be due to drugs, alcohol,
medications, or caused by other injuries or treatment for
other injuries (eg, systemic injuries, facial injuries or
intubation), or by other problems (eg, psychological trauma,
language barrier or coexisting medical conditions) or caused
by penetrating craniocerebral injury
possible objective measure of TBI severity. Recently, there has
been increased emphasis on TBI and, in particular, mild TBI in
US8 9 and UK military personnel, including development of a
screening procedure.9 10 One of the elements in this screening
procedure is the retrospective analysis of PTA.9 11 It is therefore
also an important question whether retrospective assessment of
PTA in civilian and military settings is a valid, sensitive and reli-
able measure of TBI severity, and whether it is linearly related
to severity of brain injury.
DEFINITION OF PTA
PTA consists of a disorder of episodic memory for personally
experienced events and information. Episodic memory is a form
of declarative recall particularly involving working memory. It
represents an automatic, subconscious recall of a sequence of
memories for multisensory events in an individual’s immediate
environment. Most studies of PTA, especially the seminal early
studies, have been made in relatively severely brain-injured
patients. Levin et al12 defined PTA as a period following a TBI
with loss of consciousness during which there is confusion,
amnesia for ongoing events and often a behavioural disturbance.
Russell and Smith13 considered that the end of PTA was most
easily defined as the point at which the patient could give a
clear, consecutive account of what was happening around them.
Ahmed et al14 noted that Russell and Nathan,15 in a seminal
description of PTA in 1946, emphasised that to be recognised as
out of PTA, patients had to demonstrate normal ‘continuous
memory’, meaning the ability to reliably recall events from
ongoing autobiographical memory. However, autobiographical
memory is not continuous, even in normal individuals, but is
episodic, and any account of a remembered event in normal
individuals will feature both detailed recollections and
gaps.16 17 Thus, the reliable day-to-day committal of events to
memory, and their retrieval, is a more accurate description of
the day-to-day categorical, episodic memory process than an
attempt to construe memory as a so-called continuous process.
Nakase-Richardson et al18 have conducted wide-ranging studies
of PTA and post-traumatic confusion. They defined PTA as the
interval from the event of the head injury until the patient is
orientated and can form and later recall new memories, over a
Friedland D, Swash M. J Neurol Neurosurg Psychiatry 2016;87:1068–1074. doi:10.1136/jnnp-2015-312193
Neurological education
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period of three consecutive days, a definition that follows
Russell and Nathan’s emphasis on both resolution of confusion
and restoration of recall of ongoing events as marking the end
of PTA.18–20 However, Russell and Nathan15 used a simple
notion of subjective awareness of return of awareness for every-
day events. This is a loose paradigm that is often followed by
neurologists and neurosurgeons in assessing PTA, especially in
retrospective assessment made many months or even years later.
In prospective studies after acute head injury, Russell and
Nathan15 stressed that recovery of orientation, representing
resolution of a post-traumatic confusional state, is a key element
in the resolution of PTA.
Lack of consensus on the definition of the end of PTA is gen-
erally acknowledged in studies of mild TBI.6 12 Wilson et al21
found that patients in PTA were distinct from those with an
amnesic syndrome or those with chronic memory impairment
due to TBI, a distinction characterised by semantic processing
errors, impaired verbal fluency and slowed simple reaction time,
with impaired backward digit span in the PTA group. They com-
mented that the term ‘PTA’ was misleading, since categorical
recall is not the only psychological abnormality present.22
The prominence of additional neurobehavioural manifesta-
tions including confusion, sleep-wake cycle disturbance, motor
agitation, affective lability, aggressive behaviour and abnormal-
ities in thought processes20 23 has given rise to the concept that
the term ‘post-traumatic confusional state’ should replace ‘PTA’,
a reversion to the terminology first used by Russell in
1932.15 22 However, much of the literature on outcome follow-
ing TBI, especially that related to retrospective assessment, has
focused on length of PTA, assessed by the return of the ill-
copyright.
defined notion of normal continuous memory, and not by reso-
lution of the post-traumatic confusional state. The latter,
however, can only be accurately assessed prospectively. Since the
disorder of categorical memory and the confusional state are
closely associated in the acute stage after TBI, any distinction
between the two is difficult to address prospectively or retro-
spectively.24 Tate et al25 conducted a prospective assessment of
people with severe TBI (GCS<8 in 68% of participants). They
found that, contrary to the expected sequence of recovery of
orientation followed by recovery from amnesia, recognition
memory reached criterion before orientation to place (at
19 days after injury) and 5 days sooner than orientation to time,
that is, before resolution of the post-traumatic confusional state.
In this prospective study, these researchers also noted that there
was variability in determining the end of PTA according to the
scale used for the assessment. Nonetheless, there was a close
correlation between the recovery of orientation and return of
memory. They noted that ‘in clinical terms, PTA represents a
major disturbance of the sensorium’. In this context, it is
perhaps relevant to remember that people admitted to hospital
without brain damage often do not know the date or day of the
week.
MEASUREMENT OF PTA
In clinical practice, PTA can be assessed prospectively and retro-
spectively. In the prospective measurement of PTA, scales such
as the Westmead PTA Scale and the Galveston Orientation and
Amnesia Test (GOAT) are often recommended. The Westmead
PTA Scale consists of 12 items relevant to orientation, recall and
recognition of new information. The end of PTA is taken as the
conclusion of the first of three consecutive days with a score of
12/12.6 10 26 27
Retrospective analysis of PTA is less secure. It involves asking
the individual to recount their first memory following injury.
1069
 Neurological education
The assessor deems recovery from PTA to have occurred when
he or she is satisfied that normal ‘continuous memory’ (better
expressed as normal categorical recall of memories) is being
described. Although essentially a subjective judgement, this is
the basis for the Rivermead PTA Protocol.19 Ruff et al7 made
recommendations for retrospective assessment of PTA in the
context of categorising a mild TBI. One of their key points was
that the clinician must specifically ask the patient to describe
their personal recall of events and not what they have subse-
quently learnt.7 However, in practice, recognition of learnt
material presented as a memory for events occurring after brain
injury is essentially unverifiable, both by the observer and the
patient. A further potential hazard arises when the clinician
assessing PTA is one of a sequence of assessors, instructed by
different parties, as is common in the legal context. The individ-
ual may unwittingly present learnt material rather than genuine
memories. Any later examiner is particularly vulnerable to this
error. This is also relevant in the clinical setting during the early
phase of recovery after a mild or moderate TBI when the
patient may be prospectively assessed by a sequence of different
medical and other health professionals, each asking similar,
protocol-driven questions about remembered events. This may
encourage the individual to present learnt responses, as though
forming a part of ongoing experience and, as in the retrospect-
ive context, may be difficult to recognise both by the examiners
and by the patient. The variability of prospective and retrospect-
ive assessment of PTA often carried out many years after the
injury is uncertain, although the validity of retrospective PTA is
generally accepted unchallenged by the Courts. The experience
of Tate et al24 25 suggests that retrospective PTA determination
should be subject to cautious interpretation. For example, a
patient in PTA may be capable of finding their way in a familiar
environment, implying that ecological memory is available and
effective.
PTA AND SEVERITY OF TBI—DEFINITION
The working definition of PTA has changed over the years.
From the 1960s to the early 1990s, a PTA of <1 h was consid-
ered a mild TBI, a PTA of 1–24 h was viewed as a moderate
TBI, and a PTA longer than 24 h was viewed as a severe TBI.
This definition has been modified, so that a PTA of less than a
day has become accepted as a mild TBI, a PTA of 1–7 days is
considered a moderate TBI, and a PTA of >7 days is viewed as
a severe TBI.21 A very brief PTA, duration not strictly defined,
but less than an hour, often <30 min, for example in sports
injuries, is sometimes now termed ‘minor TBI’. Currently, there
is general acceptance that a PTA<24 h is characteristic of a mild
TBI, whereas a PTA>24 h indicates at least a moderate
TBI.2 3 26 27 Nakase-Richardson et al18 have since extended this
classification system using the Mississippi Post Traumatic
Amnesia Classification System, suggesting that a PTA of 0–
14 days is viewed as a moderate TBI rather than a severe TBI. A
severe TBI would be an injury following which the PTA was
over 28 days. It is important to note that this change was based
on the long-term outcome after TBI as judged by return to
work. For example, 67% of individuals with a PTA of up to
14 days were back at work at 1 year, suggesting that the older
classification of severe TBI was not appropriate. The distinction
between a mild TBI and a moderate or severe TBI is important
given the difference in outcome following such injuries, but this
distinction is essentially a matter of convenient clinical defin-
ition, since it is self-evident that there must be a continuum in
the severity of brain injury following head trauma, with a
number of additional factors contributing to disability, including
1070 Friedland D, Swash M. J Neurol Neurosurg Psychiatry 2016;87:1068–1074. doi:10.1136/jnnp-2015-312193
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focal brain injuries, injuries to other parts of the body and
limbs, and psychological factors. The true natural history of an
uncomplicated mild TBI ranges from recovery within minutes to
months, or even years, after injury.28–30 The outcome following
moderate or severe TBI is variable and difficult to predict, often
leading to long-term cognitive and neurobehavioural difficul-
ties.28–30 Since retrospective analysis of PTA may be necessary
in order to define mild TBI,31 32 agreement on terminology is
essential.7 However, these observations suggest that it is unlikely
that PTA is linearly correlated with outcome, but this relation-
ship has not been explored. Current definitions of mild TBI use
several categories of information that are not necessarily closely
related to outcome, for example, GCS at first measurement,
which itself may be delayed for some time after the accident,
duration of PTA, duration of ‘loss of consciousness’, itself
defined loosely, and associated injuries, especially cranial injur-
ies. The validity of PTA as the sole measure of severity of TBI
has never been objectively tested.
CONFOUNDING ISSUES
There are major potential pitfalls in the retrospective analysis of
PTA. For example, Kemp et al33 studied 63 patients with ortho-
paedic injuries who had not suffered a TBI. They were followed
up about 10 weeks after injury using the Rivermead PTA
Protocol; 38% reported PTA-like phenomena. A third of these
individuals reported amnesia of 24 h or more, thus placing
them in the category of moderate TBI, despite their never
having suffered a brain injury.33 The use of analgesics, and more
specifically opiate analgesics, can affect cognition and memory
in the absence of a TBI. This is a particular problem in the pro-
copyright.
spective and retrospective assessment of PTA since opiate anal-
gesia is often given at the scene of a major accident, and during
subsequent hospital triage.
McCarter et al,34 in an important study of this issue, tested
17 non-head injured, non-traumatic orthopaedic patients given
opiate analgesics in hospital, using the Westmead PTA Scale.
Only 20% of participants tested over 4 days reached the criter-
ion of three 12/12 scores defined as indicating the end of
PTA.19 35 This result indicates that opiate analgesia can induce
amnesia resembling PTA in individuals who have not sustained a
TBI, potentially confounding assessment of possible PTA in
many head-injured patients. Anaesthesia for emergency surgical
procedures is frequently accompanied by a period of opiate
analgesia, further compromising the reliability of any prospect-
ive assessment of PTA following TBI complicated by other injur-
ies. This needs to be borne in mind in the medicolegal setting
when relying on the prospective or retrospective measurement
of PTA.
ISLANDS OF MEMORY
In the retrospective analysis of PTA, individuals may describe
isolated ‘islands of memory’ within the period of PTA. These
islands of memory occur before continuity of memory is
restored.13 14 Russell and Nathan15 pointed out in 1946 that
this can lead to an underestimation of the period of PTA. Even
if the recent definition of PTA with emphasis on the patient
being orientated and able to lay down memories that can be
recalled at a later stage is followed, identification of these
‘islands of memory’ still remains a problem. Islands of memory
are thought to be related to the experience and recall of an
event associated with a peak of arousal, or emotional experi-
ence, in the context of the TBI,36 37 a phenomenon suggesting
that learning and recall of events, at least of categorical events,
is possible during the period of PTA. Furthermore, islands of

memory are not specific to TBI. This phenomenon can have
various other causes, including opiate analgesia.34 The assump-
tion that since a patient presents islands of memory this neces-
sarily is indicative of PTA due to TBI is therefore incorrect.
ORGANIC, PSYCHOGENIC AMNESIAS AND MALINGERING
The clinical distinction between organic and psychogenic
amnesia; that is, PTA versus psychogenic dissociation occurring
in the context of post-traumatic stress disorder (PTSD) or acute
stress disorder (ASD), can be difficult, for example, in an assess-
ment made some time after the injury.37 38 Thus, it cannot be
assumed that since an individual cannot remember the details of
their injury this necessarily indicates PTA, and therefore TBI, as
it could also result from a psychological dissociation. It has been
argued that individuals with TBI, who have suffered amnesia,
are not capable of suffering from PTSD. However, the recog-
nised contemporary position is that an individual who has suf-
fered a TBI may develop PTSD, perhaps especially so in the
case of mild TBI.37 38 This is highlighted by recent research
pointing to the coexistence of PTSD and mild TBI, both in mili-
tary personnel and in civilian populations. In a meta-analysis,
Carlson et al39 found that the frequency of PTSD in individuals
with a history of mild TBI ranged remarkably widely, from 0%
to 89%, the majority of investigators reporting values between
10% and 40%. Thus, the converse assumption, that is, that the
presence of features of PTSD does not necessarily mean that the
individual did not suffer a TBI, is false. Research into malinger-
ing has focused on symptom exaggeration and the failure of
symptom validity tests in neuropsychological assessment. What
has not been considered in this research is the malingering of
PTA, that is, either making up a period of PTA or exaggerating
the length of PTA.
THE TBI NARRATIVE
Recognition of the duration of PTA is dependent on the
patient’s narrative, as interpreted by the observer. There are
very few studies considering the similarities and differences in
the narratives between individuals who have sustained a TBI
and those with a trauma-related psychological response to
motor vehicle accidents. Jones et al38 studied the trauma narra-
tives of 131 road traffic accident survivors with TBI and ASD,
focusing on mild TBI, as conventionally defined. Participants
were assessed at 1 week, 6 weeks and 3 months after TBI. At 1
and 6 weeks, the narratives of individuals with ASD/PTSD
lacked coherence. At 3 months, their narratives were still repeti-
tive. TBI was associated with confusion, defined in this retro-
spective study as uncertain memory of the event, as a separate
characteristic at all three time points. This is a unique and rele-
vant study. Nonetheless, a more precise definition of the oper-
ational criteria for identifying confusion in PTA versus amnesia
in PTSD/ASD would be helpful, especially in retrospective
assessment of PTA. Although difficult, this would be of benefit
in clinical and medicolegal settings. The problem can be likened
to symptom validity assessment in neuropsychological
practice.40
NEW APPROACHES TO GRADING MILD TBI
Concern regarding the consequences of TBI in US military per-
sonnel led the USA Department of Defense in 2008 to mandate
a screening programme designed to identify deployment-related
mild TBIs and associated residual symptoms. Iverson et al11
reviewed this postdeployment health assessment, and delineated
the specific steps at which false-positive and false-negative
screening results might emerge in determining whether or not
Friedland D, Swash M. J Neurol Neurosurg Psychiatry 2016;87:1068–1074. doi:10.1136/jnnp-2015-312193
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an individual had sustained a mild TBI. In this screening
process, the goal was to determine whether the person had
experienced signs or symptoms of TBI, including PTA.
However, as the authors acknowledge, a combatant who is psy-
chologically traumatised, physically injured or both may experi-
ence a brief period of amnesia as a psychogenic phenomenon.
In the case of physical injury, analgesics may also have been
used,11 38 a potential confounding variable in retrospectively
determining PTA. It is therefore important to recognise that
although TBI may be associated with a period of amnesia, this
amnesia may not necessarily be directly attributed to the brain
injury. It should be noted that the screening process used in the
US study has not been validated in terms of the retrospective
analysis of PTA.
Arguably, therefore, the diagnostic scenario in the medicole-
gal, civilian and military settings when a patient has sustained a
TBI, especially as assessed retrospectively, presents challenges.
PTA lasting for 2–3 days, indicative of a moderate TBI, is fre-
quently not determinable prospectively or retrospectively with
reliability because of the use of analgesia or anaesthesia required
for associated orthopaedic or other surgery. While this review
has focused on false-positive factors, this would be a scenario in
which there is also a false-negative risk, that is, falsely diagnos-
ing a patient as not having suffered a TBI when no reliable esti-
mate of the length of PTA is possible.
VALIDITY OF PTA ANALYSIS
Is retrospective analysis of PTA valid? McMillan et al31 com-
pared prospective and retrospective measurement. There was a
copyright.
high correlation between the two measurements. However, the
mean duration of PTA in these patients was 34 days, indicating
that the patients studied were at the more severe end of the
spectrum of TBI. The validity of retrospective PTA analysis in
the mild or moderate range of TBI, especially in a period when
many other factors may be concurrently influencing the situ-
ation, especially analgesia, remains uncertain. In their study of
the reliability of the Rivermead PTA Protocol, King et al6 found
that, although overall correlation was good, the test was less reli-
able when PTA was <24 h.
Ashla et al32 retrospectively assessed PTA in TBI using the
Rivermead PTA Protocol, in addition to cognitive testing. They
found that the duration of retrospectively measured PTA corre-
lated with cognitive impairments when assessed up to 5 years
after TBI. After 5 years, however, the retrospectively assessed
PTA no longer correlated with cognitive deficits. This study
was based on a small sample, consisting of 23 patients with
recent TBI and 23 with remote TBI. In addition, there is no
reference as to whether any study participants were seeking
compensation, and symptom validity testing was not con-
ducted. The latter is particularly important in assessing indivi-
duals seeking compensation.40 41 These patients were all in the
severe TBI range. When considering the validity of retrospect-
ive analysis of PTA, it would be helpful to compare the results
in a mild TBI group with those in a moderate TBI group to
test whether there was a significant difference in cognitive per-
formance. If there was such a difference, this would add
weight to the validity of the retrospective analysis of PTA using
the Rivermead PTA Protocol.
Overall, there is a paucity of studies regarding the validity of
retrograde analysis of PTA in the assessment of TBI. Sample
numbers have been small. Studies have tended to focus on the
relationship between the length of PTA, without clear definition
of its end point, and outcome.41–43 The duration of PTA,
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 Neurological education
measured quite simply in the clinical context, is viewed as one
of the most reliable indicators of outcome following TBI.41 It
has been recommended in determining the need for rehabilita-
tion management.41 43 Analysis of recall, whether defined
purely in terms of memory or taking into account other aspects
of the period of PTA, especially without consideration of other
indicators of TBI severity, limits the validity of the assessment
process.28 29 Tate et al found that amnesia resolved before dis-
orientation in 94% of 31 severely injured subjects, and that dis-
orientation resolved first for person, then for place, and then
for time.23
MILD TBI AND PTA
What can be done to improve assessment and understanding of
mild TBI? The duration of PTA is an essential but empirical
operational criterion, which should be documented as occurring
in association with confusion, and a history of alteration or loss
of consciousness of up to 24 h duration. The value of amnesia
alone without the other characteristic neuropsychological fea-
tures of the PTA syndrome (box 2) immediately after injury is
less clear. The ending of PTA should be assessed with circum-
spection, since it is a gradual process, not an abrupt phenom-
enon.23–25 In addition, the WHO definition of mild TBI stresses
the importance of recognising non-traumatic factors as possible
causes of altered consciousness and PTA.1 These non-traumatic
factors include associated physical injuries, psychological factors
including an ASD, a need for intubation and a language barrier
(box 2). Assessment of the severity of TBI in the medicolegal
setting can be contentious, especially if there have been multiple
separate assessments by different experts, and it is therefore
important to apply the WHO recommendations. In the over-
whelming majority of cases, symptoms following mild TBI remit
within 2– 3 months of injury.1 28 29 In a minority, symptoms
may be more prolonged. Although the determinants of disability
in such cases may appear to consist of personal and social
factors that are unrelated directly to the brain injury itself, MRI
and functional MRI (fMRI) studies point towards acute and
subacute changes in neural activation during this recovery
phase, predominantly affecting attentional networks in the right
hemisphere.44 45 Nonetheless, litigation, chronic pain, disrupted
sleep, and preinjury and postinjury psychiatric factors have been
consistently identified as poor prognostic factors in recovery.28
Box 2 Features of the post-traumatic confusional state
in mild, or more severe, traumatic brain injury.21
▸ Confusion (Glasgow Coma Scale 13–14/15)
▸ Episodic autobiographical amnesia for ongoing events after
the injury
▸ Retrograde amnesia (usually very brief, if present)
▸ Impaired accuracy of comprehension
▸ Impaired verbal fluency
▸ Delayed logical memory
▸ Slowed simple reaction time
▸ Impaired backward digit span
▸ Agitation and restlessness; or uncharacteristically quiet
behaviour
▸ Repeatedly asking questions. A tendency to wander
aimlessly
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IMAGING AND PTA
What is the role of MRI clinical assessment after mild TBI?
Diffusion tensor imaging (DTI) in the acute phase after mild
TBI has revealed prefrontal and frontal white matter changes,
consistent with diffuse axonal injury, as shown by initial
increased fractional anisotropy (FA), suggesting gliosis and neu-
rofilamentous compaction, and restricted mean diffusivity.44 45
In late phase images, FA is decreased, a feature considered sup-
portive of the hypothesis that it represents damage to axons in
white matter.45 However, the possible correlation of specific
neuropsychological test profiles with these changes, and their
relationship to the nature of the head injury and the symptoms
described, remains uncertain. A crucial question in mild TBI is
whether such DTI abnormalities imply long-term neuropsycho-
logical impairments and correlation of the outcome in patients
with frontal cortical abnormalities on DTI with PTA less than or
more than 24 h. The conventionally defined cut-off at a PTA of
24 h may be valid if clearly correlated with functional outcome.
In all such correlative studies, a precise definition of the clinical
features of the post-TBI state, as well as the duration of PTA,
and the associated delirium, will be essential.
For example, fMRI studies in a group of 12 concussed
American high school athletes, matched against uninjured team-
mates, showed decreased brain activation patterns in a working
memory task, associated with postconcussive symptoms and
impaired cognitive performance, with decreased reaction time.46
Abnormalities found 13 h after injury had resolved at retest
7 weeks after injury. The fMRI studies showed decreased activa-
tion of right hemisphere attentional networks in the concussed
patients relative to controls in the initial studies, with compensa-
copyright.
tory increases in activation of this network at 7 weeks. In a
second fMRI study,47 abnormalities in neural response inhib-
ition were found in regions associated with inhibitory control
and with the default mode network. The authors of these
studies stress that PTSD was not a factor in their results. Future
fMRI studies in mild TBI may help to better define post-
traumatic delirium with impaired anterograde memory, leading
to a more objective assessment procedure than the subjective
interview currently commonly used for detection of PTA, essen-
tially based on retrospective recollection, but susceptible to
learnt responses in repeated testing.
CONCLUSIONS
It should always be remembered that the episodic autobio-
graphical memory system that is tested regarding subjective
recovery of memory for daily events occurring after TBI is only
one aspect of the neuropsychological phenomenology (box 2).
Episodic autobiographical memory itself depends on encoding
and consolidation in the limbic system and prefrontal cortex,
storage in the cerebral cortex, mainly in association areas and
the limbic region, and retrieval, a function of the right fronto-
temporal and limbic regions. Procedural memory, memory
priming, perceptual memory and semantic memory are strik-
ingly uninvolved. In a critical review of the semiology and brain
localisation of these different types of memory, Markowitsch
and Staniloiu48 commented that the clinical term PTA was not
clearly defined; ‘sometimes it describes the phase after the reso-
lution of delirium that is characterised mainly by memory
impairment’ and ‘sometimes the term overlaps with delirium,
encompassing a period from injury until recovery of full con-
sciousness and memory’.
The current vague definition of PTA in retrospective assess-
ment arises from its historical context, as a relatively simple

method for detecting neuropsychological abnormality in the
immediate post-TBI period, with persistent features allowing
assessment many months, or even years later.13 15 21 22 Unlike
the assessment protocol recommended for prospective evalu-
ation immediately after TBI, retrospective assessment, long after
injury, is not robust and is open to unascertainable bias from
practice effects,49 especially when isolated retrospective memor-
ies are interpreted as occurring within the assumed context of
PTA, rather than as representing emotionally laden memories,
for example, of a bedside visit by a family member, and thus as
a normal episodic memory, occurring at a time when there was
no other observed neuropsychological abnormality, for example,
confusion (delirium). Emergence from the state of post-
traumatic delirium and amnesia is therefore not sudden and
abrupt, but gradual, and may not have an easily defined end
point. Recall by the patient of learnt material, purporting to be
recalled from within the period of PTA, whether consciously
learnt or not, is an ever-present hazard in retrospective inter-
pretation of the duration of PTA, especially when the assessment
is repeated on several occasions by different observers in the
medicolegal context. In addition, confabulated responses may
develop.
There are important clinical and, especially, medicolegal
reasons for accurately determining the severity of a TBI, particu-
larly at the milder end of the spectrum, and all available evi-
dence should be taken into account.2 For example,
misclassification of a patient who has suffered a mild TBI as
having a moderate or severe TBI may lead a clinician to suggest
that ongoing cognitive symptoms enduring for longer than
3 months are to be expected. This expectation may provoke
‘expectation as aetiology’,50 so that expectation of cognitive
symptoms becomes a self-fulfilling prophecy. The converse,
failure to identify evidence for TBI, may lead to misclassification
of an injured patient as exaggerating symptoms or as suffering
from stress-related symptoms. Psychogenic symptoms are often
considered additional to the effects of the TBI itself, but the
possibility of an organic cause for these symptoms associated
with subfrontal white matter disruption requires further study.
By itself, PTA—the simple interview to establish return to nor-
mality—is a rough and insensitive instrument for determining
these factors that is susceptible to unascertainable observer and
respondent bias.49 McNally51 memorably stated in 1950 that
‘memories are not videotapes of our experiences’, meaning that
they are not immutable records, but are encoded and recalled in
relation to external events and internal emotional experiences.
Furthermore, PTA is amnesia for current elapsing time after
brain trauma; it is not retrieval failure.
Competing interests None declared.
Provenance and peer review Not commissioned; internally peer reviewed.
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