DISPROPORTIONATE RETROGRADE AMNESIA

IN A PATIENT WITH HERPES SIMPLEX ENCEPHALITIS

Toshikatsu Fujii1,2, Atsushi Yamadori1, Keiko Endo1, Kyoko Suzuki2
and Reiko Fukatsu1,2
(1Section of Neuropsychology, Division of Disability Science, Tohoku University Graduate
School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; 2Rotman
Research Institute, Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada)

ABSTRACT

We describe a patient who developed a severe but temporally limited retrograde amnesia
coupled with a relatively mild anterograde amnesia following herpes simplex encephalitis.
The patient showed a profound retrograde amnesia for autobiographical events extending
for about 10 years prior to the disease onset. Her knowledge about public events and famous
persons was also impaired for this period. An MRI and SPECT demonstrated bilateral
medial temporal pathology. This case represents a further instance of a relatively focal
retrograde amnesia following brain damage. We review other reported cases with focal
retrograde amnesia and consider theoretical and neuroanatomical accounts for the present
case. Two factors may account for her amnesic patterns: a partial disruption of the store for
premorbid binding codes (i.e., information that multimodal feature representations occurred
synchronously); along with a relative preservation of the encoding process required to
develop new synchronous codes.

Key words: amnesia, retrograde amnesia, anterograde amnesia, hippocampus, medial

temporal lobe

INTRODUCTION

Retrograde amnesia, the inability to retrieve events that occurred prior to the
onset of brain damage, is typically accompanied by anterograde amnesia. Over
the past two decades, however, focal or isolated retrograde amnesia (FRA), i.e.,
severe retrograde amnesia in combination with relatively mild or absent
anterograde amnesia, has been reported (for reviews, see Kapur, 1993; De Renzi,
Lucchelli, Muggia et al., 1997). These FRA cases are important for theories of
amnesia and normal memory function because they provide evidence that
retrograde and anterograde amnesia are caused by disruption of different
cognitive processes that appear to be subserved by different neural substrates.
In this paper, we report a post-encephalitic patient with a severe but temporally
limited retrograde amnesia coupled with a relatively mild anterograde amnesia.

CASE REPORT

The patient was a 51-year-old right-handed (Edinburgh handedness inventory, 100)

woman with a 12th-grade education. Her past medical history included lung tuberculosis at
the age of 20 and 40, and an operation for uterine cancer at the age of forty-nine. There

Cortex, (1999) 35, 599-614

600 Toshikatsu Fujii and Others

was no previous neurological or psychiatric history. Four days before admission she had
been febrile for a day. On the day of admission (7 May 1997), she developed a generalized
epileptic seizure. On admission, neurological examination was normal except for a mild
disturbance of consciousness. Her cerebrospinal fluid showed lymphocytosis and a
significant elevation of anti-herpes simplex virus type 1 (HSV 1) antibodies. Intravenous
acyclovir was started. Intermittent complex partial and generalized seizures were eventually
controlled after four weeks. At this time she was well oriented to time, place and person,
but a severe retrograde amnesia for events prior to the onset of the disease was revealed.
Although she was able to relearn most of the past episodes of her life from her siblings,
she complained to be unable to experience these events as her own personal experiences.

NEURORADIOLOGICAL EXAMINATION

An MRI scan (1.5-T, Signa, General Electric) of the brain was carried out on
the 35th hospital day. Sagittal images were obtained to cover the whole brain.
Then, axial images parallel to the Sylvian fissure with a slice thickness of 4.3
mm were acquired. Last, oblique coronal images, vertical to the axial plane, with
a slice thickness of 4.3 mm were obtained. T2-weighted images (Figure 1)
revealed abnormal high intensity areas in the bilateral medial temporal lobes,
including the anterior two thirds of the hippocampal formation (hippocampus,
dentate gyrus, and subiculum) and the posterior part of the amygdala. The
posterior part of the hippocampal formation, perirhinal cortex, entorhinal cortex,
parahippocampal gyrus, and temporal pole seemed to be spared.

a b

Fig. 1 – Coronal (a) and Axial (b) T2-weighted MR images showing high intensity areas in both
hippocampal regions. The left side of the figures correspond to the right side of the brain.
 Disproportionate retrograde amnesia 601

SPECT using N-isopropyl(123I)-P-iodoamphetamine carried out on the 41st

hospital day showed a diminution of regional blood flow in bilateral anterior
medial temporal lobe regions.

NEUROPSYCHOLOGICAL EXAMINATION

Neuropsychological assessment was carried out between days 28 and 52.

General Cognitive Testing

The main results of the standard neuropsychological tests administered are

shown in Table I. In conversation, comprehension was normal, but there was a
mild word finding difficulty which was reflected in relatively low scores on the
verbal fluency test. The scores on the WAIS-R PIQ, on the Raven Test, and on
the Kohs Cube Test demonstrated her normal spatial and constructional capacity.

TABLE I
Patient’s Performance on General Cognitive Testing

Wechsler Adult Intelligence Scale – Revised

Full IQ 89
Verbal IQ 84
Performance IQ 96
Scaled Scores
Information 6
Digit Span 6
Vocabulary 7
Arithmetic 6
Comprehension 11
Similarities 9
Picture Completion 9
Picture Arrangement 9
Block Design 11
Object Assembly 10
Digit Symbol 9
Mini Mental State Test 29/30
Token Test (shortened version; De Renzi and Faglioni, 1978) 33/36
100 Pictures Naming 94/100
Raven PM 34/36
Kohs Cube Test IQ 115
Wisconsin Card Sorting Test (shortened version; Nelson, 1976) 4 categories with 48 cards
Verbal Fluency
Animals 8
‘A’ 7
‘Fu’ 6
‘Ni’ 2

Immediate Memory and Working Memory

The patient’s digit span was five forward and her tapping spatial span,
assessed by a modified form of the Corsi Block Tapping Test (Milner, 1971),
was six. Two tests were used to evaluate her verbal and spatial working
602 Toshikatsu Fujii and Others

memory: Lag 1 digit span (Dobbs and Rule, 1989) in which the patient had to
subtract one from each digit presented orally and report the resulting sequence
(e.g., when given 7, 9, 4, the patient has to respond 6, 8, 3) and a “Corsi” type
tapping test which demanded repetition of the patterns immediately after 90
degrees rotation. Her performance was five for both the verbal and the spatial
working memory tests. Her performances on these tasks were normal.

Anterograde Memory

Table II summarizes the results on standard learning tests. On the Wechsler

Memory Scale-Revised, the patient’s MQ was 93, which was superior to her
FIQ of 89 on the WAIS-R. Clinical observations suggested that she could learn
new information fairly well. For example, she was able to recall what her
siblings and hospital staffs had told her, as well as what she had seen on TV or
read in newspapers. She did not have difficulty in recognizing doctors and was
able to give information about the examinations she had undergone. However,
the Delayed Memory Index suggested some anterograde memory deficit. Her
performance on both the Rey Auditory Verbal Learning Test and recall of the
Rey Complex Figure Test was also in the impaired range.
TABLE II
Patient’s Performance on Anterograde Memory Tests

Wechsler MemoryScale – Revised

General Memory Index 93
Verbal Memory Index 96
Visual Memory Index 93
Attention/Concentration Index 75
Delayed Memory Index 73
Logical memory (immediate) 66 percentile
Logical memory (delayed) 19 percentile
Visual reproduction (immediate) 79 percentile
Visual reproduction (delayed) 24 percentile
Rey Auditory Verbal Learning Test
No. correct on five recall trials 6, 9, 9, 12, 9
6th trial after distraction 5
Recognition 11
Rey Complex Figure
Copy 36/36
3-min. delayed recall 10/36
Recognition Memory Test
Words 43/50
Faces 41/50

Retrograde Memory

The patient was aware of her retrograde amnesia and was somewhat perplexed
and pessimistic. She never produced confabulatory responses to our questions.

(1) A Structured Interview on Autobiographical Memory

The patient’s autobiographical memory was assessed by means of a

structured interview covering past personal experiences. Items selected for this
 Disproportionate retrograde amnesia 603

interview were based on information obtained from an interview with the

patient’s closest sister with whom the patient had regular monthly contact. Items
covered the following categories: towns and houses in which she had lived,
educational and occupational experiences, trips, hospital treatments, births,
weddings, and deaths of her relatives. The results of the structured interview
revealed a time limited dense FRA, with a duration of approximately 10 years.
Some examples of the results are given below.

Towns and Houses. She was able to describe accurately the six towns in
which she had lived until the age of 25 and the town in which she had been
living since age 25. She was also able to draw a rough sketch of a condominium
which she and her husband had bought 17 years ago. However, she was unable
to remember that they had sold it and moved to a new condominium two years
ago. She could not recall her present address and telephone number despite the
fact that she could remember the address and the telephone number of her
previous home.

Educational and Occupational Experiences. She could recall facts related to

elementary and senior high school. She could remember scenes of plays with her
brother, episodes of school outings, and the routes to the schools. She could
recall the names of her supervisors and coworkers with whom she had worked
in her early 20s, and the external shape of a building in which she had worked.

Trips. She had virtually no memory of the many trips she had taken with her
husband or siblings over the past five years. We could not collect certain
information about her previous trips.

Hospital Treatments. While she was able to remember the two episodes of
pulmonary tuberculosis from which she suffered 31 and 11 years ago, she was
unable to recall an operation for uterine cancer that had occurred just two years
ago.

Birth, Weddings, and Deaths of Her Relatives. She could recall correct name
and age of her six siblings and 10 nephews/nieces. She could not remember her
father’s onset of hemiparesis and his subsequent hospitalization that happened 10
years ago. She was unable to remember her father’s death and funeral which
occurred seven years ago. She could not remember her husband’s death and
funeral half a year ago. She had no memories about three wedding parties which
she attended one, two and five years ago respectively.

Other Experiences. When she was asked about a big earthquake which
happened 20 years ago, she answered “I might have experienced it but don’t
remember”. Later she remembered the chaos in the house caused by the quake.

On the whole, she was able to recall or recognize 80 percent (24/30) of the
events or facts that occurred more than 10 years before the onset and eight percent
(2/25) of the events or facts that occurred less than 10 years before the onset.
604 Toshikatsu Fujii and Others

On the Autobiographical Memory Interview (Kopelman, Wilson and

Baddeley, 1990), her scores on personal semantic memory were 12, 17, and four
for childhood, early adult life, and recent life sections, respectivelty, and her
scores on autobiographical incidents were five, four, and three for childhood,
early adult life, and recent life sections, respectively. She showed rather low
scores on autobiographical incidents because her recollections were sketchy and
not elaborate. Her scores for recent life both on personal semantic memory and
autobiographical incidents reflected her anterograde memory capacity because
this part includes the question about present hospitalization.

(2) Memory for Public Events

We prepared a questionnaire about public events that had occurred prior to

the onset of the disease by modifying the test devised by Fukatsu, Fujii, Sato et
al. (1994). The questionnaire consisted of 16 questions per decade, from 1950 to
1997. It was given in a recognition form with four choices per question.
The performance of the patient and 10 age- and education-matched control
subjects (mean age 49.4, mean education 13.7) are compared in Figure 2. Her
correct scores for each decade starting from the 50’s through the 90’s were 13,
12, 10, 12, and 10 respectively. The mean numbers of correct answers and the
SD of the control subjects for the same decades were 13.1 (3.0), 13.2 (2.0), 12.8

Patient

Controls
16
Correct Responses

1950’s 1960’s 1970’s 1980’s 1990’s

Decade

Fig. 2 – Performance of the patient and control subjects on the Public Event Test. Each vertical
bar represents one standard deviation.
 Disproportionate retrograde amnesia 605

(2.0), 14.8 (1.9), and 15.0 (1.2), respectively. Her performance on the questions
concerning the 90’s was more than two SD below the control score. The scores
for the other decades were within the normal range (within two SDs).

(3) Dead or Alive Test

We also assessed the patient’s retrograde amnesia with a modified version of

the Dead or Alive test (Kapur, Young, Bateman et al., 1989) adapted for the
Japanese population. The test consisted of 40 items. For each of the four
decades starting from 60’s through 90’s, eight famous persons were selected
who had died during that decade (32 items). Eight buffer items consisted of
eight living persons. The patient and five age- and education-matched control
subjects (mean age 49.2, mean education 13.6) were requested to indicate
whether a famous personality was dead or alive and, if they thought the person
was dead, when he/she had died (in 5-year bands). The test score related only to
individuals who had died. Two points were allotted for each correct dead
judgment. If the answer was incorrect, zero was allotted. A further two points
were added if the subjects could correctly indicate the time of the death within
one 5-year band-width. Thus for each decade, the maximum score was 32.
Figure 3 shows the patient’s performance and that of the control subjects.
The patient’s scores for each decade starting from the 60’s through the 90’s

Patient

Controls
32
Total Scores

16

1960’s 1970’s 1980’s 1990’s

Decade

Fig. 3 – Performance of the patient and control subjects on the Dead or Alive Test. Each vertical
bar represents one standard deviation.
606 Toshikatsu Fujii and Others

were 30, 28, 28, 10 points respectively. Mean scores and the SD of the control
subjects for the same decades were 20 (4.0), 24.4 (1.7), 25.6 (3.0), and 24.4
(6.1), respectively. The patient performed better than control subjects on the
earlier decades, but showed marked impairment for persons who had died during
the 90’s.

DISCUSSION

This post herpes encephalitis patient demonstrated a disproportionately severe

retrograde amnesia, which contrasted with a rather mild anterograde amnesia.
Her ability to acquire and retrieve new information in everyday life was fairly
well preserved, although not perfect. Formal testing corroborated this clinical
observation. In contrast, she showed a profound retrograde amnesia for
autobiographical episodes and facts extending for about 10 years prior to the
disease onset. Her knowledge about public events and famous persons was also
impaired for this period. She showed a mild word finding deficit in daily
conversation. An MRI and SPECT demonstrated bilateral medial temporal
pathology. This case represents a further instance that a relatively focal
retrograde amnesia can occur as a residual of brain damage.

The Extent of FRA and Its Etiology

Compared with traumatic brain injury, encephalitis as a cause of FRA is

relatively rare. Tables III and IV summarize reported cases of FRA in terms
of their etiologies. Excluding three cases of unknown etiology (Andrews, Poser
and Kessler, 1982; Stuss and Guzman, 1988; Dalla Barba, Mantovan, Ferruzza
et al., 1997), there are seven post encephalitic cases including the present one,
two transient global amnesia cases, an anoxia case, and a vasculitis case (Table
III). On the other hand, there are 20 cases following traumatic brain injury
(Table IV).
FRA with non-traumatic etiologies tends to have temporally limited amnesia.
Only one case of postencephalitic FRA showed amnesia covering the whole life
(O’Conner, Butters, Miliotis et al., 1992). This case had extensive damage to the
temporal lobe with some extension to the parietal lobe, posterior ventromedial
frontal region in the right hemisphere, and damage to the parahippocampal
gyrus, insula, and posterior ventromedial frontal region in the left hemisphere.
Two cases of FRA secondary to encephalitis had FRA extending for 20 to 30
(Calabrese, Markowitsch, Durwen et al., 1996) and 20 (Carlesimo, Sabbadini,
Loasses et al., 1998) years. Lesions in these two cases were smaller than those
of O’Connor et al.’s case, but larger than those of the remaining four
encephalitic cases with shorter temporal extent. In the present case, dense FRA
extended over a decade and the lesions were smaller than those of the three
cases with longer FRAs. The FRA of Hokkanen, Launes, Vataja et al.’s case
(1995) covered several years and that of Yoneda, Yamadori, Mori et al.’s case
(1992) extended only one years. The MRI of these last two cases revealed no
structural cerebral damage, but SPECT did indicate decreased blood flow in the
 TABLE III
Cases of FRA with Etiologies Other Than Traumatic Brain Injury

Authors (published year) Aetiology Age RA extension MRI or CT SPECT or PET MQ IQ

O’Connor et al. (1992) EN 26 Whole life Bil. T; Rt. > Lt., Bil. ventromedial F (MRI, CT) – 84 82
Yoneda et al. (1992) EN 21 1 year – Lt. posterior T (SPECT) – 73
Hokkanen et al. (1995) EN 33 several years – Lt. anterior-middle T (SPECT) 119 115
Calabrese et al. (1996) EN 54 20-30 years Bil. T-F; Rt. > Lt. (MRI) Rt. T-F (SPECT) 93 103
Ishihara et al. (1997) EN 29 2 years – – 116 107
Carlesimo et al. (1998) EN 29 20 years Bil. T-O-P white matter (MRI) – 89 88
Fujii et al. (this study) EN 51 10 years Bil. medial T (MRI) Bil. medial T (SPECT) 93 89
Roman-Campos et al. (1980) TGA 64 5-10 years – – 108 119
Kapur et al. (1989) TGA 74 20-40 years – – 116 111
De Renzi and Lucchelli (1993) Anoxia 26 Whole life – Bil. posterior T (PET) – 108
Evans et al. (1996) Vasculitis 61 30-40 years Bil. F, Lt. P, T pole atrophy, Lt. T infarct (MRI) Bil. F, Lt. T-P (SPECT) – 115
EN = encephalitis; TGA = transient global amnesia; FRA = focal retrograde amnesia; RA = retrograde amnesia; – = no finding; Bil. = bilateral; Lt = left; Rt. = right; T = temporal;
Disproportionate retrograde amnesia

F = frontal; O = occipital; P = parietal.

607
 608

TABLE IV
Cases of FRA with Traumatic Brain Injury (TBI)

Authors (published year) Aetiology Age RA extension MRI or CT SPECT or PET MQ IQ

Goldberg et al. (1981) TBI (severe) 36 20 years Bil. T atrophy, ventral tegmentum (CT) – 106 105
Rousseaux et al. (1984) TBI (severe) 29 Whole life Bihemispheric edema (Scanographique) – 97 99
Kapur et al. (1992) TBI (severe) 26 Whole life Bil. T; Rt. > Lt., Bil. inferomedian F (MRI) – 92 98
Markowitsch et al. (1993) TBI (severe) 45 Whole life Bil. T-F; Rt. > Lt. (MRI) – 85 100
Ogden (1993) TBI (severe) 24 Whole life Bil. medial O; Rt. > Lt. (MRI) – – –
Stracciari et al. (1994) case 1 TBI (mild) 20 1 year – Lt. F (SPECT) – –
Stracciari et al. (1994) case 2 TBI (mild) 20 1 year – – – –
Hunkin et al. (1995) TBI (severe) 19 Whole life Rt. P-O, Lt. O (MRI) – 95 111
Maravita et al. (1995) TBI (mild) 15 Whole life – – – –
De Renzi et al. (1995) TBI (mild) 19 Whole life – – – –
Lucchelli et al. (1995) case MM TBI (mild) 24 Whole life – Bil. posterior cingulate (PET) – –
Kapur et al. (1996) case GR TBI (severe) 21 Whole life Bil. T; Rt. < Lt. (MRI) Lt. T-P (PET) 83 97
Kapur et al. (1996) case SP TBI (severe) 46 Whole life Bil. T; Rt. < Lt. (MRI) – 104 94
Della Sala et al. (1996) TBI (mild) 33 Whole life – Bil. hemispheric (SPECT) – –
Toshikatsu Fujii and Others

Mattioli et al. (1996) TBI (severe) 48 20-30 years – Bil. medial T, anterior cingulate (PET) – 87
Kroll et al. (1997) case AA TBI (severe) 24 Whole life Bil. T-F; Rt. < Lt. (MRI) – 92 102
Kroll et al. (1997) case BB TBI (severe) 30 Not whole? Bil. T-F; Rt. < Lt. (MRI) – 99 104
Starkstein et al. (1997) TBI (mild) 16 Whole life – Rt. F, P, thalamus (SPECT) – 108
De Renzi et al. (1997) TBI (mild) 58 Whole life – – – –
Levine et al. (1998) TBI (severe) 36 Whole life Rt. ventral F (MRI) Normal (FDG PET) but see Note* – –
Abbreviations are the same as in Table III.
* Activation study with cued recall and H215O PET: decreased Rt. F, increased Lt. hippocampus.
 Disproportionate retrograde amnesia 609

left temporal lobe. Ishihara, Ichikawa, Takeuchi et al. (1997) reported an

encephalitic patient with a two year FRA, but no abnormalities were revealed
with imaging studies. It seems likely that, at least for cases with encephalitis, the
extent of FRA is related to the extent of their damage.
In contrast, FRA secondary to traumatic brain injury appears to be more
extensive in its duration. In at least 15 out of the 20 patients who had FRA
secondary to traumatic brain injury, FRA extented to their entire pre-injury life.
In traumatic cases, there is no consistent relation between the extent of FRA and
the lesion size, or the presence or absence of lesions detected by imaging
studies. For instance, the patients reported by Maravita, Spadoni, Mazzucchi et
al. (1995), De Renzi, Lucchelli, Muggia et al. (1995), and De Renzi et al. (1997)
had minor traumatic brain injury and no detectable lesions, and yet showed
severe FRA covering their entire life. In contrast, FRA was temporally limited in
the patients described by Goldberg, Antin, Bilder et al. (1981) and Mattioli,
Grassi, Perani et al. (1996), who suffered from severe traumatic brain injury and
had detectable lesions. However, a relatively young age of onset in traumatic
cases might mask the temporal gradient (O’Connor et al., 1992; De Renzi and
Lucchelli, 1993).

Possible Mechanisms of FRA

FRA patients cannot retrieve premorbid experiences that was normally

encoded, yet they are able to encode and retrieve information acquired after the
brain injury. What mechanisms can explain this unique pattern of amnesia? In
the following discussion, the possible mechanisms underlying FRA will be
discussed with reference to the processes of encoding, storage, and retrieval,
although in at least some of the traumatic patients without evidence of brain
damage, FRA is due to a psychogenic or functional mechanism.
Encoding deficit can be confidently ruled out as a cause of FRA in the
present case because her amnesia developed acutely after the encephalitis and
there was no evidence that she had any memory deficits prior to it.
According to current views (Teyler and Discenna, 1986; Damasio, 1989;
Kapur, 1997), two different aspects of the information related to an episode must
be stored to ensure its successful retrieval: the multimodal representations of the
episode and the information that these representations occurred synchronously.
The latter was named binding codes (Damasio, 1989), index (Teyler and
Discenna, 1986) or index codes (Kapur, 1997). Nadel and Moscovitch (1997)
also distinguished index from feature information of episodes. If these
hypotheses are correct, we can separate at least three kinds of memory engrams,
i.e., feature representations, binding codes, and connecting pathways between the
two, which also are regarded as a kind of memory engram in the sense that an
association between the two is encoded and retained for later retrieval.
The disruption of binding codes can adequately account both for impaired
retrieval of premorbid episodes and preserved retrieval of postmorbid episodes,
provided we make the assumption that the process involved in producing codes
for synchronicity of information is separate from that devoted to their storage. If
the same neural substrate were utilized for both processes, their damage would
610 Toshikatsu Fujii and Others

also result in anterograde amnesia for postmorbid events. Selective damage only
to the stores of binding codes would lead to the FRA. If damage to the stores of
binding codes dealing with premorbid episodes is complete, FRA would cover
the whole life. If it is partial, FRA would be temporally limited as in the present
case. Along this framework, O’Connor et al. (1992) surmised that their patient’s
FRA was attributable to the extensive damage both to the right and the left
parahippocampal regions, where binding codes necessary for the retrieval of
remote information are supposed to be stored.
An alternate view is that damage to the pathways connecting binding codes
with feature representations has the same effect as the disruption of the binding
codes themselves. This hypothesis could account for the FRA of Carlesimo et
al.’s patient (1998) who had damage to the white matter in bilateral temporo-
occipito-parietal lobes and showed temporally limited retrograde amnesia and
relatively preserved ability to learn new information. This hypothesis may be
applicable to patients with temporally limited FRA with subcortical or posterior
cortical lesions, but not to cases with FRA covering the whole life, because it is
difficult to believe that complete damage to the pathways would leave new
learning intact. Certainly this view cannot explain the present case who had
neither subcortical nor posterior cortical lesions.
A related but different theory proposes that brain damage may cause a
distortion (Lucchelli, Muggia and Spinnler, 1995) or an elevation of the
threshold (Della Sala, Freschi, Lucchelli et al., 1996; De Renzi et al., 1997) of
the patterned matrices, but leave engrams themselves and machinery for storing
and retrieving new information undamaged. In fact, the traumatic FRA of
Lucchelli et al.’s (1995) case 2 and the total FRA of Stuss and Guzman’s (1988)
patient cleared suddenly, leaving no detectable residual deficits. This hypothesis
can account for FRA after mild traumatic brain injury.
Other authors claim that it is not the disruption of binding codes but that of
feature representations which is responsible for FRA. Ogden’s (1993) patient
showed a retrograde amnesia which was accompanied by visual deficits and loss
of visual imagery after bilateral medial occipital lesions. Based on Damasio’s
(1989) framework, Ogden postulated that the patient’s autobiographical memory
loss was a result of his inability to retrieve long-term visual memories (see
Rubin and Greenberg, 1998). Evans et al. (1996) similarly argued that FRA was
caused by the destruction of representations of consolidated memories or of
critical intracortical connections. These explanations seems implausible because
it is unlikely that damage to feature representations can cause severe FRA and at
the same time leave intact not only the functioning of semantic memories, but
also the capacity to learn new information (De Renzi and Lucchelli, 1993;
Hunkin et al., 1995).
Another explanation of FRA as a storage dysfunction is the consolidation
deficit theory proposed by De Renzi and Lucchelli (1993) who reported an
anoxic case of FRA with abnormal forgetting rate. Maravita et al. (1995)
reported a similar case following mild traumatic brain injury. Problems inherent
to the consolidation theory concerns the extent of FRA (Evans et al., 1996;
Hunkin, 1997). This theory may be applicable to cases with relatively short
extent of FRA, but it cannot explain FRA of longer duration or covering the
 Disproportionate retrograde amnesia 611

entire life, unless we assume consolidation continues over decades. The present
patient showed the extent of FRA of about 10 years and a low delayed memory
index on the WMS-R. If consolidation is assumed to last this long, this
explanation is consistent with the present case.
Finally, we must consider the possibility of a retrieval deficit as a cause of
FRA. As some researchers pointed out (De Renzi and Lucchelli, 1993; Della
Sala et al., 1996), it is implausible that damage to the retrieval process itself is
so selective as to affect premorbid information only without damaging newly
learned postmorbid information, unless we male the unlikely assumption that
there are different retrieval systems for premorbid and postmorbid information
(Maravita et al., 1995; Levine, Black, Cabeza et al., 1998). In fact, in a case
with basal forebrain amnesia who showed a pure retrieval deficit, retrieval
recovered for both information acquired before and after the onset of infarct
(Fukatsu, Yamadori and Fujii, 1998).
To sum up, a partial disruption of stores of binding codes formed
premorbidly and a relative preservation of the encoding process for new binding
codes is the most plausible hypothesis to account for the present patient’s
amnesia, i.e., severely impaired retrieval of episodes covering 10 years predating
the disease onset, and relatively preserved encoding and retrieval of episodes
that occurred after the disease. Alternatively, a deficit in consolidation process
can explain her amnesic profile if we assume that the consolidation activity
remains active as long as 10 years.

Neuroanatomical Consideration

The present patient had lesions in the bilateral medial temporal lobes, as
evidenced by both MRI and SPECT studies. It was hard to determine more
precise lesion sites in this type of cerebral pathology. In this regard it is
interesting to note that most reports of FRA come from traumatic brain injury or
encephalitis, suggesting that multifocal (and probably bilateral) lesions are
necessary for patients to manifest FRA (Markowitsch, 1995; Kapur, 1997).
As shown in Table III, four of the patients with encephalitis, including the
present case, had bilateral temporal lobe damage. The remaining two cases
showed an abnormality in the left temporal lobe on SPECT. Evans et al.’s
(1996) case with a vasculitis showed structural damage to the left temporal lobe
and De Renzi and Lucchelli’s (1993) case with an anoxia showed some evidence
of bilateral temporal pathology on PET. Among the patients with traumatic brain
injury who had relatively circumscribed damage (see Table IV), seven out of 13
cases showed damage in the temporal lobes and one showed bilateral reduction
of metabolism in the medial temporal lobe by PET. Researchers who have
reported FRA in patients with lesions not encroaching upon the temporal lobes
(Odgen, 1993; Hunkin et al., 1995; Levine et al., 1998) have stressed the role
played by damage to the connection between the lesions and the temporal lobes.
Thus it is likely that the dysfunction of the temporal lobes is a prerequisite for
the development of FRA. If this is the case, there must be a distinction amongst
specific temporal lobe regions concerning encoding, storage, or retrieval
processes.
612 Toshikatsu Fujii and Others

The present patient showed damage relatively restricted to the bilateral

hippocampal formations, with possible sparing of the posterior part of the
bilateral hippocampi. The temporal pole, perirhinal cortex, entorhinal cortex and
parahippocampal gyrus appeared to be undamaged bilaterally on MRI. Bilateral
damage of CA1 of the hippocampus is known to produce moderately severe
anterograde amnesia with minimal retrograde amnesia, while bilateral damage
extending beyond CA1 region, but still limited to the hippocampal formation,
can produce more severe anterograde amnesia along with extensive temporally
graded retrograde amnesia covering 15 years or more (Zola-Morgan, Squire and
Amaral, 1986; Rempel-Clower, Zola, Squire et al., 1996; Squire and Zola,
1996). Reed and Squire (1998) also reported two cases with lesions in the
bilateral hippocampal formation who showed anterograde amnesia and retrograde
amnesia limited to the decade preceding the onset of amnesia. The two other
patients with more extensive damage beyond the hippocampal formation had
severe anterograde amnesia and more extensive retrograde amnesia. From these
results, it can be inferred that the CA1 region of the hippocampus is important
for memory encoding but contributes little to retrieval of remote memories.
As to the roles of the remaining parts of the hippocampal formation and
adjacent temporal cortices, we can advance two hypotheses. One is that the
remaining parts of the hippocampal formation and the adjacent temporal cortex
are involved both in encoding and storage/retrieval. The other is that these areas
are mainly specialized for storage/retrieval. Both assumptions can explain the
findings of Squire and his colleagues because additional storage/retrieval deficits
can enhance anterograde amnesia (see Nadel and Moscovitch, 1997). Yoneda,
Mori, Yamashita et al. (1994), based on the study of amnesia following herpes
simplex encephalitis, also suggested that anterograde amnesia is related to the
reduced hippocampal volume, while retrograde amnesia is related to the atrophy
of the parahippocampal gyrus. Therefore, for FRA to occur, the encoding
function of either hippocampus should be maintained. Many authors also
emphasized the importance of the integrity of either hippocampus in cases with
FRA (Kapur, Ellison, Smith et al., 1992; O’Connor et al., 1992; Markowitsch,
Calabrese, Liess et al., 1993; Hunkin et al., 1995; Evans et al., 1996; Kroll,
Markowitsch, Knight et al., 1997; Carlesimo et al., 1998; Levine et al., 1998). In
the present case, although damage to the hippocampus (MRI) and hypoperfusion
in the medial temporal region (SPECT) existed, we would like to consider that
encoding process of either hippocampus must have functioned relatively well. In
fact, the patient’s ability to learn new information was not totally normal, which
can be attributable to a certain degree of dysfunction of the hippocampal
encoding system. But possible bilateral medial temporal lobe damage within or
adjacent to the hippocampal formation must somehow have contributed to the
disruption of stores for binding codes.
Acknowledgements. We wish to thank Dr. K. Jin for referring the patient to us; DT
Stuss, M. Moscovitch, B. Levine for their comments on a draft and help with improving
the English text.
Part of this study was supported by grants in-aid (08279103) to A. Yamadori for
scientific research from Ministry of Education, Science, and Culture of Japan, and by JSPS-
RFTF97L00202 from the Japan Society for the Promotion of Science.
 Disproportionate retrograde amnesia 613

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Toshikatsu Fujii, Section of Neuropsychology, Division of Disability Science, Tohoku University Graduate School of Medicine, 2-1,
Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. E-mail: fujii@mail.cc.tohoku.ac.jp

(Received 6 April 1999; accepted 24 May 1999)