Neurocase

The Neural Basis of Cognition

ISSN: 1355-4794 (Print) 1465-3656 (Online) Journal homepage: http://www.tandfonline.com/loi/nncs20

Profound anterograde amnesia following

routine anesthetic and dental procedure: a
new classification of amnesia characterized by
intermediate-to-late-stage consolidation failure?
Gerald H. Burgess & Bhanu Chadalavada
To cite this article: Gerald H. Burgess & Bhanu Chadalavada (2015): Profound anterograde
amnesia following routine anesthetic and dental procedure: a new classification of amnesia
characterized by intermediate-to-late-stage consolidation failure?, Neurocase, DOI:
10.1080/13554794.2015.1046885
To link to this article: http://dx.doi.org/10.1080/13554794.2015.1046885

Published online: 15 May 2015.

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Date: 20 October 2015, At: 07:50

Neurocase, 2015
http://dx.doi.org/10.1080/13554794.2015.1046885

Profound anterograde amnesia following routine anesthetic and dental procedure: a new
classication of amnesia characterized by intermediate-to-late-stage consolidation failure?
Gerald H. Burgessa* and Bhanu Chadalavadab
a

Department of Clinical Psychology, University of Leicester, Leicester, UK; bConsultant Psychiatrist, Northamptonshire Healthcare
Foundation NHS Trust, Northampton, UK

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(Received 12 December 2014; accepted 27 April 2015)

Anterograde amnesia caused by bilateral hippocampal or diencephalon damage manifests in characteristic symptoms of
preserved intellect and implicit learning, and short span of awareness with complete and rapid forgetting of episodic
material. A new case, WO, 38-year-old male with anterograde amnesia, in the absence of structural brain changes or
psychological explanation is presented, along with four comparison cases from the extant literature that share commonalities
between them including preserved intellect, span of awareness greater than working memory, and complete forgetting within
hours or days following successful learning, including notably for both explicit and implicit material. WOs amnesia onset
coincided with anesthetic injection and root canal procedure, with extended vasovagal-like incident. The commonalities
between the ve cases presented may suggest a shared biological mechanism involving the breakdown of intermediate-tolate-stage consolidation that does not depend on the structural integrity of the hippocampi. Speculation on the mechanism of
consolidation breakdown and diagnostic implications are discussed.
Keywords: anterograde amnesia; memory; neuropsychological assessment; consolidation; accelerated long-term forgetting

Milners (Scoville & Milner, 1957) detailed assessments of

Henry Molaison ushered in the modern understanding of
the basis of human memory functioning. Her ndings,
which documented the characteristic symptoms of medial
temporal lobe (MTL) amnesia, have been replicated time
and again in numerous subsequent case studies. A review
of 147 cases of restricted bilateral hippocampal (or fornix)
lesions found in common a selected profound anterograde
amnesia and span of awareness for unfolding events that
did not far exceed that of working memory (i.e., seconds
to minutes), in the context of preserved intellect, everyday
executive ability, and working memory (Spiers, Maguire,
& Burgess, 2001). Notably, implicit learning is commonly
intact in these cases, evident in the capacity to learn and
then retain new motor procedures or skills, and via demonstration of priming effects in ofce-based testing.
Amongst these 147 cases were also inconsistencies
(Spiers et al., 2001). For example, there was marked
variability in the presence and extent of retrograde amnesia, a phenomenon of forgetting ones past, thought to be
caused by a ceased and thus permanently incomplete consolidation process, or due to blocked access or retrieval of
stored information. When retrograde amnesia occurs in the
context of neurological damage, it manifests as temporally
graded, meaning more distant, well-consolidated memories are generally remembered and those nearer to the
point of neurological onset are not. Vast individual variably amongst the cases in duration of retrograde amnesia
*Corresponding author. Email: gb222@le.ac.uk
2015 Taylor & Francis

from moments before neurological onset, to encompassing

ones entire lifetime, were reported.
Memory is formed via a bottleneck (Markowitsch,
1996) complex that incorporates multiple inter-connected
structures within and between the MTL, fornix, and the
diencephalon. Damage to any of these areas bilaterally
causes the manifest symptoms of organic amnesia, though
damage to diencephalon structures tend to be additionally
characterized by marked and extended autobiographical
retrograde amnesia, severe temporal order confusion, and
confabulation (Gold & Squire, 2006; Kopelman, 2002).
The amygdaloid complex plays an auxiliary yet vital role
in new memory formation due to its extensive neural networks and role in tagging the emotional valence and
personal or biological signicance of information
(Christianson, 1992; McGaugh, 2004). MTL and diencephalon amnesias are categorized as organic amnesia due
to their distinctive and relatively consistent features, and
traceable path to damaged brain structures known to be
involved in the formation of new memories.
Much less clear and much less clearly dened are
amnesias of the so-called psychogenic or functional type
(De Renzi, Lucchelli, Muggia, & Spinnler, 1997), which
by denition occur in the absence of structural brain
changes, the former usually associated with psychiatric
co-morbidity or feigning, and the latter dened by uncertainty of physiological or psychological, and in any case
unknown, cause. Dissociative amnesia, on the other

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G.H. Burgess and B. Chadalavada

hand, is a classiable diagnosis with set criteria (Spiegel

et al., 2011), established in part due to the existence of a
critical mass of known cases with shared characteristics,
and transparent linkage to established psychological theories (e.g., psychological defense mechanisms).
Dissociative amnesia is associated with severe acute psychological stress or trauma, which manifests as sections of
ones past and/or identity being made inaccessible to the
conscious awareness of the individual, whilst new episodic
learning ability tends to remain relatively intact.
Anterograde amnesia in the absence of structural brain
damage is rare, or at least rarely reported. There are four
known cases, documented separately (De Renzi &
Lucchelli, 1993; Kessler et al., 1997; Markowitsch,
Kessler, Kalbe, & Herholz, 1999; Smith et al., 2010),
which as yet have not been compared and contrasted to
each other and that is what we endeavor to do in this
article. Additionally, we present a fth, original case
report, WO with an unexplained profound anterograde
amnesia that has persisted indenitely, and which directly
followed a medical emergency in a dentists ofce involving anesthetic injection and root canal procedure in
March 2005. Our aim is to compare all ve cases, and
investigate whether preliminary conclusions and consistent
features may be derived about these cases as a group, we
hope for the sake of initiating a process toward establishing a more precise and specic diagnostic category, understanding of the mechanism of consolidation failure, and
importantly treatment options.
Case report
WO is a left-handed, male, UK National who was
38-years-old at the time of the dental procedure that preceded the onset of his amnesia, married with two children,
and ranked in the military, stationed abroad.
Developmentally, he was of normal birth, met milestones
appropriately, and was an average student. Previously t
and healthy, he joined the army at age 17, is a Gulf War I
veteran, and married at age 22 his wife to whom he is still
married.
Signicant medical history includes a coccyx injury in
1989 with minor but persistent complications, and he
presented to his general practitioner (GP) in February
2005 with increased back pain. He had a history of hypertension, but which was reportedly normal at the time of the
dental appointment. Once in his early thirties following
alcohol consumption, WO became unrousable for an hour
during a hypnotism stage show, and he did not fully regain
a normal level of conscious awareness until the next day.
WO had no previous psychiatric history or mood disturbance, and was in good standing in the military and in
his role as a husband and father. There is no history of
mental illness in his family. His grandfather had Lewy
bodies dementia and died of complications several days

before the incident-in-question, to which WO and his

family ew back to the UK for his funeral, then back
abroad. WOs grandmother had angina, and his mother
developed type II diabetes, and later suffered a stroke.
Incident description and aftermath
WO attended a routine dental appointment for root canal
treatment at 13:40 hours. He was injected with the anesthetic, Citanest with Octapressin 3% just prior to the
beginning of treatment. He wore tinted dental glasses,
obscuring a view to his level of responsiveness. The
procedure was completed at 14:30 hours, and at this time
it became apparent that WO was pale and faint, and could
not get himself up when re-positioned from the supine to
the upright position. Records and observations indicated
that he was vacant and with slow speech. A vasovagal
incident was suspected, and WO was provided with dextrose tablets and high-ow oxygen. By 17:00 hours his
condition had not improved, and he was taken by ambulance to emergency, in which he remained an inpatient for
3 days. Whilst an inpatient, and for the succeeding month,
WO exhibited only a 10-min span of awareness for events,
after which he had no memory. This improved to an
approximately 90-min span of awareness, where it has
remained to date. There are no observable or reported
physical/mobility impairments. He reportedly experiences
constant tinnitus.
Initial assessment and diagnosis
While still abroad, WO was referred to psychiatry from
neurology because no clear neurological basis for his
symptoms could be found. Initially WOs symptoms
were thought to be an atypical reaction to the anesthetic,
with possible subsequent cerebral damage. This was investigated as felt appropriate by EEG and brain scans (CT,
MRI, and later SPECT), which were normal, and by
neuropsychological testing, which was abnormal. The
emphasis on diagnosis shifted from organic to psychogenic, and initially classied as a dissociative amnesia.
Orientation and mental status
Several months post-onset, it became apparent that WOs
condition had not improved, and he and his family
returned to his childhood home in the UK, which his
mother had vacated. WO knew the house, local amenities,
and geography, which aided in his orientation and selfmanagement of the condition. Though over the years WO
has implicitly adjusted to his circumstances to some
extent, in general each morning he is surprised to wake
up in his mothers house. He wakes up believing that he
should still be in the military, stationed abroad. Every day
he thinks it is the day of the dental appointment.

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Neurocase
Through prompting by his wife, WO checks his computer each morning on which they have listed (and keep
updated) key facts he should be aware of. Some events
that have occurred since the onset of his condition in
March 2005 continue to elicit genuine surprise or astonishment each time he sees or hears about them, such as the
marriage of some family friends or that a family pet has
since passed away. WO manages his daily life and generally remains oriented throughout the day via the use of
continuous access to an electronic diary and prompts.
Technically apt, he learned to use satellite navigation and
a new digital camera prociently, and he originally problem solves other tasks each time, such as how to turn on
the power to his familys new television. He drives himself
to appointments through the use of satellite navigation,
and/or previous familiarity with the region in which he
lives. Preserved ability to parent and deal effectively with
emergencies has been demonstrated. His wife reported
subtle differences in his ability to cope with stress or
multiple demands on his attention, and he reportedly
becomes more easily frustrated and intolerant and takes
less interest in everyday family affairs, though his personality otherwise remains largely intact.
WO has remained completely oriented to his own
identity, and that of his family, though he expects everyone
to still be the age they were in March 2005. He has written
down his childrens current schools and achievements, and
wifes new job. When ofce-based assessment sessions
lasted more than 90 min, WO became completely disorientated to time and place, if kept from referencing his
electronic calendar, appointment letter, or a clock. Though
we have seen WO on multiple occasions, he demonstrates
no recognition of ever having seen us before, and we must
start afresh with introductions each time we meet. He is
attentive socially, though requires his wife to answer questions regarding events since March 2005 that he has not
otherwise written down and/or reviewed within the last
hour or two. If asked, he may say, I know I have a
memory problem, or I think it is March 2005, but it is
not, based on the daily reviews of his notes. Typical of
known cases of amnesia, he has not lost knowledge of the
purpose and use of clocks and calendars which help to
keep him orientated, and he has maintained relevant, personal information and about the use of objects in the
environment.
Current general intellectual and cognitive skills
WO sat neuropsychological testing on four occasions
between June 2005 and May 2012. His digit span (i.e.,
working memory) was assessed at each session (Wechsler,
1997a). WO initially scored in the low average range (16th
percentile) in 2005, but subsequently improved though
never surpassed the 50th percentile, and generally he
remained a standard deviation or more below an adult

reading test-estimated premorbid IQ between the 75th

and 84th percentiles. The visuo-spatial equivalent, spatial
span suggested preserved performance at the 84th percentile (Wechsler, 1997b). WO scored in the upper percentiles
(i.e., 63rd and above) on all executive functioning tests he
was administered, several with timed components.
WOs current IQ/verbal comprehension (i.e., word
knowledge, facts, and verbal reasoning) tested at the
63rd percentile (Wechsler, 1997a). His perceptual organization (i.e., visual reasoning and spatial construction)
tested at the 84th percentile. Conclusions drawn from
these results suggested that WO was of above average
intelligence, and somewhat stronger visuo-spatially than
verbally/numerically, and it would appear that his cognitive skills (i.e., working memory and visuo-motor clerical processing speed) had diminished somewhat from
pre-amnesia-onset levels at the 37th percentile.
Explicit learning and memory
Memory testing results are outlined in Table 1. Reected
in these scores are WOs everyday reported symptoms,
namely that he could learn new material, but if that material was not recalled or rehearsed within a 90-min timeframe, it was lost completely. WOs initial learning
capacity appeared to have improved from the rst months
following amnesia onset to a year or more after onset, and
he selectively learnt certain types of material more effectively, for example reproducing a complex geometric gure after having copied it, or recalling the details of a story.
He was least effective at learning a random list of 15
unrelated words (5th percentile overall), and was somewhat less effective on face recognition in the context of
other evidently exceptional visual memory abilities. He
demonstrated more effective list learning when words
could be chunked into semantic categories, in other
words he effectively utilized encoding strategies inherently
offered in the tests design.
Extending the timeframe of WOs retention of
acquired/learnt information was possible by asking him
to recall or recognize (i.e., call back into conscious awareness) what he had learnt before the expiration of 90 min
had elapsed since the learning trial(s). Through use of this
procedure, he was able to recall precisely the same items/
material at 110 min as he had at 30 min. Evidence suggested that he either acquired/learnt information, or he did
not. In other words, following the standard 30-min delay,
he only tended to recognize that which he could also only
previously and independently freely recall. Cueing was of
little, if any, benet in improving his scores. Furthermore,
his score on immediate recall trials tended to be precisely
replicated (even in phraseology or approach) to that of his
delayed recall, if elicited from him before 90 min had
elapsed. Decay, even what may be considered normal
decay, of the memory trace did not occur before 90 min

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Table 1.

G.H. Burgess and B. Chadalavada

Results of memory testing (20052012).

June 2005 (1 Day of Testing) 3 months post-onset*

MEMORY & LEARNING
WMS III (Wechsler, 1997b)
Story Memory
Story 30-min Delay
Visual Reproduction
Visual Reproduction 30-min Delay
RAVLT (Rey, 1964)
Immediate
Delayed
October 2006 (2 Days of Testing) 19 months post-onset
MEMORY & LEARNING
WMS-III Story Memory
Immediate Recall 1st Story
Immediate Recall 2nd Story (rst reading)
Immediate Recall 2nd Story (second reading)
Immediate (Story) Memory (overall scaled score)
Story Recall at 95-min Delay
Story Recognition at 95-min Delay
KBNA (Leach, 2000)
List Learning Immediate Trial
List Learning 30-min Delay
List Learning plus additional 80-min Delay (110 min)
List Recognition Delayed
Complex Figure Immediate
Complex Figure 30-min Delay
Complex Figure plus additional 80-min Delay (110 min)
Picture Recognition at 95-min Delay
AMIPB (Coughlan & Hollows, 1985)
List Learning Immediate
Interference List Trial
List Learning Post-interference
Design Learning Immediate
Interference Design Trial
Design Learning Post-interference
January 2008 (2 Days of Testing) 34 months post-onset
MEMORY & LEARNING
WMS-III
Story Memory Immediate
Story Memory 30-min Delay
Story Recognition 30-min Delay
Faces Immediate
Faces 30-min Delay
CVLT (Delis, Kramer, Kaplan, & Ober, 1987)
Immediate
95-min Delay
95-min Cued Delay
95-min List Recognition
IMPLICIT LEARNING
Reverse-image Mirror Maze (Day 1, seconds) Day 2, seconds
Trial 1
Trial 2
Trial 3
Trial 4
Trial 5
Trial 6
Trial 7
Total Errors (Day 1) Day 2
May 2012 (1 Day of Testing) 86 months post-onset
RETROGRADE AMNESIA
Headline News & Social Events (recognition knowledge of)

Low
Low
Low
Low

average
average
average
average

Impaired
Impaired

76% recalled
24% recalled
36% recalled
37th percentile
Nil
Chance
37th percentile
63rd percentile
Same as above
37th percentile
91st percentile
98th percentile
Same as above
Nil
5th percentile
<5th percentile
<5th percentile
63rd percentile
90th percentile
16th percentile

75th
84th
75th
25th
50th

percentile
percentile
percentile
percentile
percentile

50th percentile
Nil
A few items guessed
Just above chance
(49 s)
(35 s)
(30 s)
(27 s)
(24 s)
(23 s)
(23 s)
(2) 1

49
43
33
30
24
23
23

s
s
s
s
s
s
s

(continued )

Neurocase
Table 1.

(Continued).

20012002
2003
2004
January to March 2005 (amnesia onset March 2005)
Rest of 2005
2006
2007

4/7
1/9
2/7
0/2
0/4
0/5
0/6

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Note: *The 2005 scores were derived from WOs rst neuropsychologists report, which were reported only as classication labels, not percentiles; for the
sake of clarity, low average represents the 9th to the 24th percentiles, and impaired represents <5th percentile.

had expired he retained precisely the same amount. WO

was extremely susceptible to proactive and retroactive
interference. When administered interference trials on
word lists or design learning, or read two different stories
back-to-back, his performance was drastically impacted,
either by rapidly forgetting a large portion of the content
from the rst trial, or becoming much less effective in
learning the second.

Implicit learning and memory

Implicit learning was not evident in WOs test-based performance through perceptual priming or via demonstration
of savings on reverse-image mirror maze completion,
when tested on exactly the same material after a 3-day
delay. Perceptual priming was assessed using silhouetted
and distorted animal or object forms. On the rst day, WO
was instructed to guess what 30 distorted forms were and
achieved a score of 25/30. Of those he guessed incorrectly,
he was provided the correct answer and asked if he could
or could try to perceive it as that particular animal or
object? The results of this strategy were mixed in that he
reluctantly agreed that only two-of-the-ve could be the
named animal or object. On the second administration 2
days later, he scored 24/30 missing the exact same items
with exactly the same incorrect guesses, plus one he had
previously guessed correctly.
WO was also presented two objects which were rst
presented in very distorted form, then pictorially rotated
through stages eventually revealing a very clear twodimensional prole image of the object. WO was
instructed to guess what the object was as soon as he
was able, with successive rotations of the object. Day 1
was considered an opportunity to prime his response for
Day 2, and it was hypothesized that he would correctly
guess the objects with fewer rotations on Day 2. This did
not occur; he guessed the objects after exactly the same
number of rotations as Day 1, and again he made the same
incorrect guesses on precisely the same frames as Day 1.
Also on Days 1 and 2, WO was provided a paper-andpencil maze that he was instructed to complete as quickly
as he was able without making contact with the pencil to
the maze boundaries, and that this had to be completed

through sight of only a reverse-mirror image. He was

administered the maze multiple times, in order to learn
the task and reach a plateau of speed in completing the
task. This is a task that is considered to require new motor
or procedural learning, and those with bilateral hippocampal damage are able to improve and then retain the new
motor skill over subsequent days (Milner, Corkin, &
Teuber, 1968). It was expected that WO would demonstrate the same pattern of retention, but he did not. On Day
1 he demonstrated normal learning, increasing speed and
made fewer errors across six trials. WOs performance on
Day 2 was for all intents and purposes a replica of his
performance on Day 1. On Day 2 he demonstrated no
savings in the time it took to complete the trials, nor did
he make signicantly fewer errors, but instead he demonstrated a very similar course or pattern of learning, beginning on trial one as if a novice performance, and then
progressing similarly to that of Day 1. Table 1 delineates
his times and errors across successive trials.

Retrograde amnesia
WO reported that he recalled personal events up to the day
of amnesia onset in March 2005, including receiving the
anesthetic and commencement of drilling for the root
canal. This would suggest an absolute minimal episodicautobiographical retrograde amnesia. In 2012 we assessed
his memory for 40 news events, interspersed major headlines between September 2001 and September 2007 (see
Table 1). He could explain in great detail world events that
led up to the First Gulf War and the ground assault that
began in mid-March 2003. He did not recall or recognize
subsequent key events of that war. WOs memory for news
events was patchy between 2001 and 2004, and seemingly
complete amnesia thereafter. Interestingly, however, he did
recall that a Tsunami occurred in southeast Asia
(December 2004), indicating that, we did a fund-raiser
for that (in early 2005), thus linking this event to a
personal (autobiographical) episode, presumably the catalyst of its permanence in his memory. Conclusions drawn
from this suggest that events personally experienced, of
personal signicance (i.e., episodic-autobiographical
memories), were more likely to be remembered than

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G.H. Burgess and B. Chadalavada

impersonal news events (i.e., semantic/impersonal episodic memories).

have attempted to map onto and discuss in regard to the

presenting features of WO and the four comparison cases.

Episodic learning since March 2005

General comparison of WO with four similar cases of

anterograde amnesia
Initially, what is striking about WO and the four comparison cases (De Renzi & Lucchelli, 1993; Kessler et al.,
1997; Markowitsch et al., 1999; Smith et al., 2010), in the
absence of structural damage, is their specic resemblances to particular cardinal features of bilateral organic
amnesia, namely profound anterograde amnesia, with
intact intellect and everyday executive ability and personal
identity. Retrograde amnesia is variably represented and
characteristically temporally graded amongst these cases,
demonstrating the classic Ribot effect, as is the case with
organic amnesias (Spiers et al., 2001). Dissimilar to amnesias involving direct damage to diencephalon structures,
there is an absence of temporal confusion and confabulation All ve of these individuals were reported as of at
least average intelligence, and it was not suspected that
drugs or alcohol, trauma, or feigning illness/malingering
was the cause of their symptoms, though psychological
peculiarities were attributed in two cases (i.e., cases known
as AA, FL). Four-of-the-ve comparison cases (exception
AA) were of sudden onset, preceded by a medical emergency/event. It was not common that a loss of consciousness, other than brief (FL) was caused by the preceding
injurious event; however, the four cases of sudden onset
did demonstrate a subsequent period of altered consciousness (e.g., stupor, disorientation, incoherent speech) lasting between hours to days after the event.
The primary feature that draws these ve cases
together for comparison is the existence of anterograde
amnesia in the absence of a known and/or detectable
neurological event preceding it, and in the context of at
least insufcient MRI structural brain imaging evidence
that would appear to justify and/or explain the extent and
profound nature of the amnesia. PET/SPECT scan evidence was equivocal, and in any case (PI, TA) did not
demonstrate hypometabolism in any region known to be
particularly associated with the consolidation of memory.
Each of these cases shares a span of awareness for events
that exceeds that of working memory, which suggests that
the engram or memory trace evaporates at some later stage
than the immediate, as would be typical in organic amnesia. The range of span of awareness was reportedly
between a minimum of 5 min and a maximum of
13 days, though the authors indicated that these two
extremes may be accounted for by extremely poor effort
(Kessler et al., 1997) and no opportunity to assess over
subsequent days following testing (De Renzi & Lucchelli,
1993), respectively.
Similar to cases of organic amnesia, retrograde amnesia demonstrated the classic Ribot effect and manifested as

Without known precedent to us, amongst people with

anterograde amnesia, WO has made one new memory
since amnesia onset. He also extended recognition memory beyond his usual 90 min (more than 24 hr in fact) on
one occasion for a newborn baby in a photo. This coincided with his being on an experimental 12-week trial of a
cholinesterase inhibitor. This recognition did not transfer
into permanent memory storage, however, and it remains
unclear precisely when that trace faded permanently. The
other, permanent memory successfully stored occurred in
regard to the death of his father in 2005, which occurred
after the amnesia onset. WO does not recall the episode of
his fathers death (though he was at his bedside all day),
but does have an awareness or the knowledge that his
father is deceased.

Language
Initially, in the rst few days following amnesia onset,
WO reportedly presented with slowed, slurred speech,
and with comprehension difculties. Though this has
improved over the years, WO still may exhibit semantic
paraphasias (e.g., calling the wardrobe, shed) and circumlocutions (e.g., little yellow bits for corn) in his
spontaneous speech. Informal screening of confrontation
naming and his ability to comprehend and follow multistaged commands detected no abnormalities from 2006
forward, though that year (in March) WO experienced an
acute expressive aphasic incident that persisted for 2
weeks, characterized by extreme word-nding difculties
and labored speech. No medical reason for this incident
was detected.

Discussion
The particular sets of symptoms presented in this article
are extremely difcult to categorize neurologically or psychically in either of the two widely used classication
systems, DSM-5 (American Psychiatric Association,
2013) and ICD-10 (World Health Organization, 1993).
Several lines of speculation have so far been considered
in an attempt to understand the mechanism of consolidation failure, which will now be reviewed. We have had athand multiple assessments over years with WO, and four
cases from the extant literature that share remarkable similarities and some differences between them (see Table 2
and Appendix 1 for comparisons). Additionally we had
empirical research and theories of memory consolidation
that appear may have some relevance, and of which we

PI

30 years
Female
Neck injury/car accident

29 years
Male
None known, stress related to
independence and university demands
attributed
Gradual (over 1 month)
N/A
510 min (authors attribute to extreme
poor effort)

NAD

NAD

Posterio-superior
temporal
cortices

PET/SPECT evidence of
brain region
hypometabolism

Left Pons (brain stem)

NAD

No

8 + months not assessed prior to

onset, though reported as
normal
No

Minimal

Burgess & Chadalavada

(current article)

WO

No

No

2 months complete,
4 years patchy

Minimal

Variable

Variable

6.8% less hippocampal NAD

volume compared to
controls bilaterally
(within 1 SD of
control norm)
Not reported
NAD

Possibly perceptual
priming, but not
motor skills
No

Decades nearly
complete

Minimal

Worse

Worse

38 years
Male
Anesthetic/root canal/
possible period of
hypotension
Sudden
Sudden
No
Unknown
Sleep for 4 hr + results 90 min
in onset of complete
amnesia
Seems likely,
Yes
extrapolating from
the case report
Worse
Worse

51 years
Female
Neck injury/car
accident

Smith et al., 2010

FL

Notes: * Denotes De Renzi and Lucchelli were not able to assess on successive days, therefore the duration before amnesia onset is unknown precisely, though extrapolating from the text, it appeared that
PIs span of awareness was greater than 24 hr; NAD denotes no abnormalities detected; N/A denotes not applicable.

NAD

Yes

No

1 year patchy

Complete

No

Not completely assessed

Complete

Not reported

Worse fading trace with time

Much worse impoverished

Equivalent

Implicit memory/learning
evident in ofce-based
tests
Co-morbid personality
disturbance
MRI

Equivalent

Better

Equivalent

Worse

Better

Equivalent

Working memory relative to

current IQ
Immediate memory recall
relative to current IQ
30-min delayed recall
relative to current IQ
Retrograde amnesia for
personally experienced
events
Retrograde amnesia for news
events

No (memory traces from test

content fade with time)

No, or not known

Sudden
Brief
2 hr

Markowitsch et al., 1999

TA

Kessler et al., 1997

AA

Extended span of awareness/ Yes

retention with rehearsal

De Renzi &
Lucchelli,
1993
Age at onset
24 years
Sex
Male
Preceding event
Thoracic/cervical
trauma/
cyanotic
Onset
Sudden
Loss of consciousness
No
Span of awareness for events Between 4 hr and
13 days*

Author and year reported

Initials

Table 2. Comparison of anterograde amnesia cases.

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7

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G.H. Burgess and B. Chadalavada

variable along time and content axes, though an apparent

selective preference for the preservation of episodic autobiographical memories (in three cases up to the point of
amnesia onset) over episodic impersonal (e.g., headline
news stories) memories was evident. Dissimilar to organic
amnesia, the preservation of implicit learning was not a
foregone conclusion, with only one case possibly evincing
perceptual priming (FL), and no case evincing retention of
motor/procedural learning over successive days. This
would appear to suggest that all forms of learning were
vulnerable to loss at a later stage than the active learning
stage, whether episodic/semantic or procedural.
Neuropsychologically, other trends amongst the comparison cases included a relatively better visual learning
system (compared to verbal) when learning involved
spatio-constructional tasks, such as a complex geometric
gure copy and recall. Face recognition, on the other hand,
tended to demonstrate relatively poorer learning, and in
two cases impoverished (PI, AA).
Considering for a moment the medical events that
preceded amnesia onset, it was difcult to ignore the fact
that three-of-the-ve comparison cases involved spinal
column trauma, and four cases were sudden onset following a medical emergency of some kind, giving the impression that some physiological stress or trigger initiated the
amnesia, and AA was reported to be in a chronic state of
psychological stress with more gradual onset. WOs medical event was not obviously related to spinal or central
nervous system trauma, though he presented to his GP a
few weeks before the amnesia onset with increased back
pain from a previous coccyx injury. His amnesia was
causally or coincidently precipitated by an anesthetic
injection in the mouth and root canal procedure, coinciding with a possible extended period of vasovagal or hypotensive incident, which unbeknownst to the dental team
treating him, could have been 40 min. Case PI reportedly
experienced a period of anoxia and/or hypotension.
An unusual manifestation of psychogenic amnesia?
In an attempt to explain WOs symptoms, early evaluators
attributed his presentation to a psychogenic amnesia. In
considering this, it is noteworthy that in the case of AA,
described by Kessler and colleagues (1997), the gradual
onset of persistent anterograde amnesia was attributed to
the psychological torment and avoidance associated with
vocational stress and adult responsibilities. As was mentioned earlier, WOs grandfather died a few days before
the amnesia onset, and WO and his family made a brief
trip back to the UK for the funeral. This event and its
associated stress was initially attributed as the cause of
WOs amnesia and subsequently he was diagnosed with
dissociative amnesia.
It has become apparent, however, that though this
explanation may be true for some with such amnesia

symptoms, WO does not share similar personality features

as AA, quite the opposite actually, and though WO was
close to his grandfather, it was difcult to consider this
event having caused WO sufcient distress to manifest in
so profound an illness, nor does this brand of amnesia
match existing diagnostic criteria of psychogenic or functional amnesias that, for example, characteristically
involves a period of acute stress and a relatively greater
proportion of retrograde (in particular autobiographical)
rather than anterograde amnesia (Piolino et al., 2005;
Spiegel et al., 2011).
Widening the denition of accelerated long-term
forgetting?
WO and the others share similarities with reported cases of
accelerated long-term forgetting (ALF), a phenomena
associated with temporal lobe epilepsy, characterized in
part by normal volume hippocampi and normal performance on 30-min delayed recall in standardized neuropsychological memory testing, but then followed by
atypically accelerated and extensive forgetting over several days or weeks, compared to healthy controls (Blake,
Wroe, Breen, & McCarthy, 2000; Elliot, Isaac, & Mulhert,
2014; Muhlert, Milton, Butler, Kapur, & Zeman, 2010).
Epilepsy is not indicated in WO or the comparison cases,
and none have been witnessed having any type of seizure
(including absence) or unusual transient perceptions or
behaviors, and all demonstrated normal EEGs.
Furthermore, ALF occurs at a slower rate (i.e., days-toweeks compared to minutes-to-hours), demonstrates a ushaped retrograde amnesia rather than the classic Ribot
temporal gradient, and crucially implicit or procedural
learning remains intact in ALF (Elliot et al., 2014;
Muhlert et al., 2010), all features that would appear to
describe a different type of amnesia, or at least later-stage
and independent mechanism of consolidation failure than
the current cases under discussion.
It is compelling to consider ALF further, however,
since ALF shares the remarkable similarity to the cases
presented herein of signicant forgetting well past the
phase of short-term or working memory, and because
studies have attempted to link ALF with structural hippocampal damage, and have not found an association. Butler,
Bhaduri and colleagues (2008), using MRI evidence,
found that hippocampal volume was associated with learning capacity and retention at 30 min, but not to ALF,
suggesting that ALF may be caused by a more diffuse
physiological process rather than due to the structural
integrity of the bilateral hippocampi per se. Indeed, evidence in support of this notion came from Magnetic
Resonance Spectroscopy (MRS), that in the context of
normal volume hippocampi, metabolic abnormalities
were discovered in the right hippocampus in people
demonstrating ALF, specically a decrease in the N-

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acetylasperate ratio compared to healthy controls, suggesting a sort of metabolic dysfunction may relate to the ALF
phenomena (Tramoni et al., 2011).
A previously latent congenital or acquired metabolic
disorder?
Following on from Tramoni and colleagues ndings, an
intriguing speculation was whether the mechanism that
caused the forgetting was the prevention or inhibition of
metabolic processes involved in memory formation. Most
intriguing was the function of new messenger ribonucleic
acid (mRNA) protein synthesis, which coincidently gets
initiated roughly during the intermediate-to-late stage of
memory consolidation (i.e., 10 min to 24 hr after learning),
congruent with the time period of forgetting amongst the
cases, and is the de novo mechanism that is responsible for
the eventual permanence of memories, involving the restructuring of synapses (Bekinschtein et al., 2007; Carew
& Sutton, 2001; McGaugh, 2000; Medina, Bekinschtein,
Cammarota, & Izquierdo, 2008; Ng & Gibbs, 1988). If
this speculation were to hold merit, the structural integrity
of the hippocampi or other brain regions would be less
relevant than an individuals capacity to metabolically
process and synthesize proteins responsible for microscopic structural changes in the synapses, and the longer
span of awareness would be backed-up by a plausible,
temporally congruent hypothesis, worthy of further investigation. What is further intriguing and tting, is that in
animal and human studies both explicit/episodic and
implicit/procedural memory works along a similar timeline
to consolidate, and each ultimately appears to require
mRNA protein synthesis for permanent memory storage
(Brashers-Krug, Shadmehr, & Bizzi, 1996; Igaz, Vianna,
Medina, & Izquierdo, 2002; Luft, Buitrago, Ringer,
Dichgans, & Schulz, 2004).
New learning in the context of anterograde amnesia
The case of WO revealed, to our knowledge, a unique
capacity for learning in the context of profound amnesia,
namely that he made two memories that extended his usual
90-min span of awareness. It may be noteworthy that one
of these memories occurred in the context of a one-off, 12week trial of a cholinesterase inhibitor, that perhaps a
chemical intervention extended his retention for 24-plus
hours, before again the trace was permanently lost. The
other incident of, in this case permanent, new learning was
the awareness WO gained about his father dying or being
deceased, which occurred after the onset of WOs amnesia.
The amygdaloid complex is a powerful auxiliary to learning, tagging the personal or biological signicance of an
event or information, and it is proximal and makes
multiple connections to brain structures whose primary
function involves learning/memory (Cahill, Babinsky,

Markowitsch, & McGaugh, 1995; Markowitsch &

Staniloiu, 2011; Turnbull & Evans, 2006). WO was very
emotionally bonded to his father, and his death carried a
great deal of personal signicance. Neuropsychological
testing evidenced that WOs retention of information
could be refreshed if recalled back into conscious awareness before 90 min had expired, a means of extending
awareness and retention also seen in ALF cases (Jansari,
Davis, McGibbon, Firminger, & Kapur, 2010). It seems
plausible that WO could have brought the engram of his
fathers death into conscious awareness on multiple occasions during the day his father died, keeping it refreshed,
and presumably could have carried on in this manner
throughout tful REM and non-REM periods of sleep,
creating the necessary elements that stamped a permanent
awareness or feeling into long-term storage.

Conclusion
Based on the cases presented herein, it may be surmised
that the anatomical integrity of the MTL, diencephalon, or
basal ganglia/striatum structures are not all that is necessary in the consolidation of explicit and implicit memories.
We set out in this article to describe a new case of anterograde amnesia alongside four similar cases that share
astonishing similarities between them, and yet do not t
within any existing neurological or psychiatric disorder or
diagnostic category. None of these cases exhibited evident
structural brain damage, but yet likely at least by the rst
nights sleep, complete and profound forgetting occurs, in
the context of intact learning, intellect, and identity. This
speed of forgetting is slower than witnessed in cases of
organic (MTL or diencephalon) amnesia (i.e., seconds to
minutes), but faster than the phenomena of ALF observed
in some cases of temporal lobe epilepsy (i.e., days to
weeks). Furthermore, while procedural learning remains
intact in organic and ALF cases, in the comparison cases
presented herein, procedural learning is not sustained,
following successful learning. We have suggested that a
plausible explanation due to two key coincidences is a
breakdown of mRNA protein synthesis, which coincides
with the intermediate-to-late stage of memory consolidation and appears responsible for the permanence of both
explicit and implicit/procedural memories. Future research
should include further investigating this stage and mechanism of consolidation in humans perhaps through the use of
fMRI or MRS, reasons for metabolic failure whether
genetic or acquired, and possibly chemical treatments, of
which a cholinesterase inhibitor potentially demonstrated
promise, enhancing recognition memory in WO. Overall,
this brand of amnesia needs another diagnostic or classication category than any currently existing, as between the
cases presented in this article, a small but critical mass of
distinctive qualities compose them, and the mechanism

10

G.H. Burgess and B. Chadalavada

appears different to other types of amnesia, as subsequently would any choices of treatment.
Disclosure statement
No potential conict of interest was reported by the authors.

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Appendix 1: Rated criteria (from most shared to least shared) for symptoms of anterograde amnesia amongst the ve comparison
cases
A

Profound anterograde amnesia.

No evidence of structural brain changes/damage from CT/MRI and normal neurological examination.
Preserved intellect/executive ability.
Preserved personality/identity.
Span of awareness for events that exceeds working memory.
Absence of identiable psychiatric trauma or psychiatric diagnosis preceding onset.
Not believed to be due to conscious feigning/malingering.
Not due to alcohol or drugs.
Prior to onset leading productive (i.e., work/school/family) life.
Symptoms persist indenitely (in absence of identied treatment).
Concurrent but non-permanent motor/procedural learning.
Better visual memory for complex/visuo-spatial material than verbal material and face recognition memory.
Retrograde amnesia occurs within a temporal, not selective, gradient and personally experienced events (i.e., episodicautobiographical) are better preserved than impersonal (e.g., news headlines).
C Perceptual priming/classical conditioning demonstrated?
Physical injury precedes/initiates onset? In particular back/neck injury?
Vasovagal/anoxic/cyanotic episode precedes onset?
Sudden or gradual onset?
Fading memory trace directly subsequent to active learning phase or preserved trace up until denite point?
Memory trace refreshed and subsequently extended via recall back into conscious awareness?
Hypometabolism in specic brain region, evident by PET/SPECT?
Consolidation failure at what point (5 min to 13 days, or with 4+ hr sleep)?
Working memory and information processing speed reduced relative to IQ?
D Transient recognition memory extended with cholinesterase inhibitor?
E Co-morbid personality/motivational disturbance. Possible incentive for symptoms (i.e., avoidance of individuation/immaturity).
New learning in highly emotive and unique circumstances.
Anesthetic injectionand/orroot canal procedure preceded onset.
Belief system about the nature and limitations of ones own amnesia inuenced performance (i.e., perceptual priming or recognition
memory after 24 hr when nights sleep purportedly causes complete amnesia).
A: All ve cases demonstrated this characteristic.
B: All who were or could be assessed for this characteristic demonstrated it (rest is missing data).
C: Controversial (clear, convincing evidence amongst cases that contradict each other).
D: Seemingly convincing evidence, though assessed/reported in only one individual (i.e., could be true of others, but was not assessed).
E: Unique features in one individual and not represented in other individuals.