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Severe anterograde amnesia with onset in childhood as a result of

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									                                                                                                                            braini0305




                                                                                                    Brain (1997), 120, 417–433


Severe anterograde amnesia with onset in
childhood as a result of anoxic encephalopathy
Melinda Broman,1 Arthur L. Rose,1 Gwendolyn Hotson2 and Christine McCarthy Casey1

Departments of 1Neurology and 2Radiology, SUNY Health             Correspondence to: Arthur L. Rose, MD, Box 118, Division
Science Center at Brooklyn, New York, USA                         of Pediatric Neurology, SUNY Health Science Center,
                                                                  450 Clarkson Ave, Brooklyn, NY 11203, USA




Summary
Our patient (M.S.) had an abrupt onset of amnesia due to a         and nonverbal logical abilities developed to adult levels.
respiratory arrest at the age of 8 years and has been followed     Neuropsychological examination at the age of 27 years
by one of us (A.L.R.) for 19 years. A specially designed MRI       elicited a pattern of memory deficits similar to those found
study indicated that the neuroanatomical localization of his       in a case (H.M.) of known mesial temporal lobe damage in
lesion is restricted to the hippocampal formation bilaterally.     adulthood. The neuropsychological pattern revealed those
Comparison of M.S.’s present IQ and academic scores with           aspects of cognitive development that do, and those that do
earlier scores revealed that his literacy skills, certain basic    not, require intact memory. The limitations to intellectual
language functions and vocabulary development were                 development imposed by severe amnesia in childhood are not
arrested by his memory disorder. In contrast, develop-             pervasive, but rather, are limited to specific types of abilities.
ment of mathematical skill was less curtailed, and verbal

Keywords: amnesia; memory dissociations; brain damage; childhood disorders

Abbreviations: NJH   National Jewish Hospital; SS       standard score; WAIS-R Wechsler Adult Intelligence Scale—
Revised; WISC-R    Wechsler Intelligence Scale for Children—Revised; WMS-R Wechsler Memory Scale—Revised


Introduction
Case reports of severe persisting anterograde amnesia have         years (Ostergaard, 1987), and a less well-documented case
identified the neuroanatomical structures that may control          of acute encephalopathy, which resulted in diffuse cerebral
memory functions (Damasio et al., 1989). In a few adult            injury followed by recovery with residual anterograde
patients, both detailed neuropsychological and neuro-              amnesia (Wood et al., 1989). Two additional cases were
pathological studies have been done (e.g. Corkin, 1984;            reported recently in an abstract form (Vargha-Khadem
Zola-Morgan et al., 1986). Such cases have contributed to          et al., 1992). Another case reported by Vargha-Khadem
theoretical models of memory (Shimamura, 1989). These              et al. (1994) is of combined amnesia, agnosia and alexia
patients retained previously acquired knowledge and have           with onset at age 13 years.
relatively spared general intelligence, including language            In the case of M.S., examination of spared versus
functions and nonlanguage cognitive functions, but they            affected neuropsychological functions over the years since
are unable to acquire new information. In contrast,                the onset of his amnesia, allowed us to address several
the amount of information available on childhood-onset             questions pertaining to the study of memory and amnesia.
amnesia is very limited; very few patients have been               (i) What are the long-term effects of amnesia on learning
reported, there are no pathologically verified cases and,           and cognition over the course of childhood development?
most importantly, there is little knowledge of the effects         (ii) Does amnesia of relatively early onset cause a global
of childhood-onset anterograde amnesia on the child’s              limitation of learning and cognitive development? (iii) If
subsequent cognitive development. To date, only two                not, how does the pattern of spared versus affected abilities
neuropsychological case studies of childhood-onset                 compare with the pattern found in adult amnesia of similar
amnesia have been published: a well-documented case                severity and pathology? (iv) Finally, how does the present
of bilateral mesial temporal sclerosis in a child aged 10          case compare with other cases of childhood-onset amnesia?
© Oxford University Press 1997
418     M. Broman et al.

Case history                                                   pressure was 400 mm of H2O. Spinal fluid cell count
Medical history                                                and glucose were within normal limits, total protein was
M.S. was born in New York City on May 6, 1962                  70 mg%; and bacterial cultures were negative. He was
following a full-term, uneventful pregnancy and delivery       treated with intravenous Solumedrol, phenytoin 6 mg/kg
with a weight of 8 lb 3 oz. His early growth and               and penicillin. He remained in deep coma for 12 h. At
development were normal. At the age of 1 year he               the time of extubation after 24 h, he was responsive and
developed asthma, and by the age of 7 years he was             oriented, but showed marked impairment of memory. An
hospitalized four times because of asthmatic attacks. When     EEG showed generalized slowing and a brain scan with
                                                               potassium perchlorate block was read as abnormal due to
he was 7.5 years old, he had a severe asthmatic attack
                                                               areas of increased bitemporal uptake.
associated with ‘passing out’ and peripheral cyanosis which
                                                                  On December 30, 1970, he was transferred to New
failed to respond to subcutaneous epinephrine. He was
                                                               York Hospital where it was noted that his memory
admitted to the local community hospital and was treated
                                                               impairment was limited to recent memory. His EEG
with oxygen and intravenous infusion of Solumedrol.
                                                               remained markedly abnormal with diffusely slow 2–4 Hz
Endotracheal intubation was performed 10 h after admission
                                                               high voltage activity. Spinal fluid examination and brain
and 2 h later, he suffered cardiac arrest but was quickly
                                                               scan were repeated and were reported as normal. It was
resuscitated with cardiac massage and artificial respiration.
                                                               concluded that he had suffered an anoxic brain injury
The duration of loss of consciousness was not recorded,
                                                               and he was discharged 1 week later on maintenance
but was probably quite brief. He was weaned off the
                                                               phenytoin therapy.
respirator 12 h later and made a complete recovery.
                                                                  On return to the NJH in January 1971, M.S. experienced
   At 8 years of age, in April 1970, M.S. was sent to
                                                               a severe adjustment reaction. He exhibited a marked
the National Jewish Hospital (NJH) in Denver, which
                                                               personality change: he stayed by himself in his room
specializes in the treatment of severe respiratory diseases.   playing with his toys. Previously he had been a leader of
He underwent an extensive diagnostic evaluation and a          his peer group, but now he became the subject of teasing
diagnosis of moderately severe steroid-dependent asthma        and ridicule by other children because of his memory
was made. He was treated with prednisone 40–50 mg on           difficulties. He exhibited temper outbursts. He developed
alternate days, theophylline 8 mg/kg/dose every 6 h, and       various somatic symptoms, including dizziness, nocturnal
ephedrine 1 mg/kg/dose every 6 h. On June 14, 1970, he         enuresis, encopresis and abdominal pains. For a period
had a generalized tonic–clonic seizure which lasted 4 min.     of several weeks, he developed involuntary movements
Diagnostic evaluation, which included serum electrolytes,      involving his face, arms and legs. A neurological evalua-
calcium, magnesium, phosphorus, spinal fluid examination        tion, which included three EEGs, was negative. It was
and an EEG, was normal. He was treated with phenobarbital      concluded that his symptoms were of an emotional nature
which was gradually discontinued after 2 months. He            due to depression and an anxiety state. He also complained
remained relatively well until the Christmas vacation when     of frequent ‘scared feelings’ which were interpreted to
he returned to visit his parents in New York City.             represent panic reactions.
   On the second day home, he had another generalized             After 2 years, phenytoin therapy was discontinued, but
tonic–clonic seizure which lasted ~45 min and was              6 months later M.S. had another generalized convulsion.
associated with vomiting and cyanosis. He was brought to       At that time, an electrographic seizure was recorded for
the emergency room of a local hospital where 17 mg of          the first time during an EEG recording and it was
intravenous diazepam was given following which the             associated with one of his usual ‘scared feelings’ (see
seizure stopped but a respiratory arrest occurred.             below). Since then, M.S. has been experiencing two types
Endotracheal intubation was performed and he was               of partial complex seizures. (i) Minor staring episodes
mechanically ventilated. His temperature was 103° F,           with brief loss of contact which occur a few times a
pulse 180 beats/min, BP ‘within normal limits’. Physical       week. These atypical absences are sometimes preceded by
examination was otherwise normal. He was apneic and            ‘scared feelings’, epigastric discomfort and/or nausea. (ii)
non-responsive to painful stimulation. Optic disc margins      About once a month, he experiences confusional episodes
were blurred bilaterally, deep tendon reflexes were present     with automatisms which may last 2–3 min with a brief
and plantar responses were extensor. The first blood gas        post-ictal period followed by rapid recovery. His current
showed a pH of 7.21 and sodium bicarbonate was given           anticonvulsants are Dilantin 250 mg/day and carbamazepine
intravenously. He was maintained on a respirator and           1000 mg/day. He has not had a major generalized seizure
several blood gases showed good oxygenation. Three             for many years.
hours after the respiratory arrest his blood pressure rose
to 220/150. Because of a fever of unknown origin, lumbar
puncture was performed after a dose of intravenous             School and social history
mannitol (1 g/kg) was given. During complete relaxation        M.S. attended kindergarten, first and second grade in a
and after disconnection from the respirator, the opening       public school where he was thought to be a superior
                                                                      Childhood onset severe anterograde amnesia       419

student despite frequent absences due to asthma. At the         course of their conversations, it became apparent to his
time of his anoxic insult, he was in the middle of second       psychiatrist that M.S. was not able to recall incidents and
grade at the NJH. Following the anoxic event, he returned       factual material to which he had been exposed in previous
to the NJH and then, 6 months after the onset of his            sessions, or minutes before. For example, M.S. was not
memory difficulties, he returned to New York, where he           able to recall the route to the doctor’s office, or recall
presented a severe management problem for his parents           receiving a coin from his mother, minutes before, to
due to his temper outbursts and ‘scared feelings.’ He was       demonstrate a coin trick. Dr Christ’s efforts to teach M.S.
placed in a special class for children with normal              school-related material, such as a poem and the arithmetic
intelligence and major health problems. In that setting, his    tables, was the subject of a book chapter (Christ, 1984).
behaviour gradually deteriorated and attacks of asthma          In the same chapter Christ documented a startling lack of
became more frequent and severe. He also developed a            personality development in his patient between the ages
disturbance of sleep pattern with violent nocturnal             of 12 and 19 years. Remarkably, M.S. demonstrated little
disruptions. In August 1972, he was re-admitted to the          apparent self-consciousness about his memory problem. He
NJH for further treatment during which he attended classes      engaged his efforts toward compensating for it in various
in the hospital school. His behaviour there included refusal    ways, e.g. by developing algorithms for the multiplication
to take medications, aggressive acts against his peers,         tables that he was unable to memorize by rote.
especially at night, and several episodes of running away.         At present, according to his parents, M.S. is unable to
He was treated with the tranquillizer Mellaril and, twice       remember recent events or learn new facts unless they are
a week, psychotherapy. In September 1973, he was placed         repeated many times. He forgets conversations and repeats
in a New York City special education programme for              the same questions 20 min later. He cannot go out alone
learning disabled children. M.S’s. school adjustment was        because he is likely to get lost. He does not remember
poor due to his extreme oversensitivity to real or perceived    requests to perform domestic chores such as washing
insults and his aggressive behaviour. Shortly thereafter, he    dishes, sweeping, or wiping the table unless he is given
was transferred to a private special school, the League         a note with specific instructions. At the flea market, he
School. At the age of 18 years, he was enrolled in a            does not remember the price of the merchandise he is
sheltered workshop which he resented because most of his        selling and has to refer to the price tag.
peers were mentally retarded. This placement was terminated        On the other hand, he will persevere for lengthy periods
because of fighting with other students and episodes of          at a puzzle like Rubics cube until he solves it and,
running away, and he was subsequently taught by a home          recently, he has become very skillful at some computer
tutor. At the age of 21 years, another sheltered workshop       games. He is able to repair or assemble such items as
was tried and it failed for the same reasons as the first        jewellery, plumbing, toys and a canopy tent.
one. Following this, M.S. went through a difficult period
of easily provoked rage reactions and violent outbursts,
during which he had to be physically restrained. He was         Neurological examination
treated with psychotherapy and haloperidol, and on one          M.S. is a stocky and muscular right-handed young man.
occasion had to be admitted to a psychiatric in-patient         His most recent (1993) physical examination was completely
hospital. Over the years M.S’s. behaviour gradually             normal apart from some wheezing on auscultation of the
improved and he began to help in his father’s retail shop       chest. The cranial nerves, motor and sensory neurological
with simple tasks. When his mother retired as a school          examination was normal. He was friendly, cooperative,
teacher, and his father sold his shop, the family started a     affable, and showed a good sense of humour with a
flea market business ‘to give M.S. something to do’. The         Witzelsucht quality. He conversed freely and fluently and
family spends winters in Florida where they continue to         his speech was quite clear. He had good insight into his
operate their business. M.S. loads and unloads the truck,       memory impairment, and he stated, ‘I don’t watch TV
sets up their stand, runs simple errands and collects money     news because I don’t remember them anyway’. He was
from customers under his parents’ supervision. M.S. has         oriented in 3D, but he did not know the location of the
no friends or social contacts outside his family.               hospital. He knew his home address, telephone number,
   M.S. entered psychotherapy at an early age (6 years)         the name of his neurologist and his psychologist, the
because it was believed that his asthma might have              names of his brother and sister, and the names of his
psychogenic basis. Initially he attended an out-patient child   three nephews and his niece, elaborating, ‘I can remember
psychiatry clinic (Kings County Hospital). Four years           things that don’t change.’ He knew that he had spent the
after his anoxic episode and subsequent behaviour change,       winter away from New York City, but he could not name
he entered individual psychotherapy with a psychiatrist         the state (Florida) or the town (Pembroke Pines). However,
(Dr A. E. Christ). He was 12 years old. At the time of          he was able to describe his parents’ condominium building
initiation of psychiatric treatment for his behaviour prob-     in Florida. He could not name the state where his brother
lems, it was not evident either to his parents or his           resides and whom he had visited recently (California), nor
psychiatrist that M.S. had a memory problem. During the         the title of his favourite video movie, which he had seen
420     M. Broman et al.




several times (‘My Cousin Vinny’) or his favourite TV       morning or what he had eaten for lunch an hour earlier.
show (Gilligan’s Island), but he reproduced the words and   He knew that his father drove him for his hospital
melodies of the signature songs of his two favourite TV     appointment, but he could not describe his father’s car.
shows. He did remember that the location of his last flea
market was ‘Aqueduct’, but he could not recall what types
of merchandise he was selling there. He thought that Mr     Examination of retrograde memories
Dinkins (Mayor of New York City) was the President of       When M.S. was interviewed at the age of 28 years, he
the United States, and he named the seasons of the year     remembered the name of the school, ‘PS 203’ (Public
in the correct order only after some prompting. He did      School 203) that he had attended from the age of 5–8
not remember what TV programmes he had seen that            years. He could not visualize the features nor could he
                                                                            Childhood onset severe anterograde amnesia            421




Fig. 1 MRI scans. Oblique-coronal T1-weighted images of the patient (A and C) and an age-matched normal control (B and D) are
shown. Images A (patient) and B (normal control) are through the amygdala 27 mm behind the temporal tip; A and B are blown-up
views of the region of the amygdala. Images C (patient) and D (normal control) are through the hippocampus 45 mm behind the
temporal tip; C and D are blown-up views of the region of the hippocampus. Both sets of images were generated perpendicular to the
plane of the temporal horn. Note the difference in size of the hippocampus (C versus D) and the similarity of the amygdala (A and B).


remember the names of his kindergarten teachers, or first             this first hospitalization at the NJH that lasted for 6
and second grade teachers. He recalled staying with                  months, until the time of his anoxic insult at 8.5 years.
relatives in Denver just before his admission to the NJH             He correctly named his homeroom teacher, Mrs N., his
at the age of 8 years. He remembered his two female                  counsellor, Robin B. (‘the one with the long hair’), and
cousins (‘girls with blond hair’) and a male cousin (‘a              his gym teacher, Mr K. He also remembered that Mr K
boy with dark hair’) in that family. He remembered several           nicknamed him ‘Smiley’—‘because I was always smiling’.
members of the hospital staff that he encountered during             He remembered and named his two best friends in the
422     M. Broman et al.

hospital, twin boys, Ronnie and Donny B. He recalled            with TR/TE of 400/16, in the coronal plane with TR/TE
that the hospital consisted of two separate buildings which     of 500/14 as well as 3000/92. Slice thickness was 4 mm.
were connected by a tunnel and that the tunnel was used            Representative images are illustrated in Fig. 1. No foci
on Saturdays and Sundays only to reach the main cafeteria.      of signal abnormality were demonstrated anywhere within
He recalled that initially all the boys were housed on the      the limbic system (amygdala, hippocampus, parahippo-
second floor of the hospital and later they were moved to        campus, cingulate gyrus, fornix, hypothalamus, thalamus,
the first floor which was shared by boys and girls. He            red nucleus, temporal lobe or cerebellum). Areas of tissue
was able to visualize his hospital room which had four          destruction may be missed on routine MR acquisitions and
beds and he sketched a correct layout of the room which         even on long TR/long TE images, particularly tissue
he shared with two other boys. He did not remember their        destruction occurring intrauterine or during early childhood.
names, but he remembered that one of them was a ‘black          However, most destructive lesions and many mass lesions
boy who was very friendly.’                                     do demonstrate abnormalities of T2 signal. Three punctate
   M.S. stayed at the NJH twice. The first hospitalization       foci of prolonged T2 signal were present in the periatrial
occurred before and the second, after the anoxic event.         white matter, two on the left and one on the right. These
We were able to establish that the above-cited memories         findings are non-specific and of uncertain significance.
referred specifically to events that occurred during his first,      The mamillary bodies appeared normal in size on the
pre-anoxia, hospitalization at the NJH.                         sagittal images. The ventricles were within normal range
   On the other hand, he had no recollection of the summer      in size and there was no enlargement of either cortical or
bungalow at the Rockaways, a beach community, where             cerebellar sulci.
he had stayed with his parents at the age of 6 years. He           The striking abnormality on the MRIs was loss of
did not remember a major family event, the coming of            volume of the medial temporal grey matter bilaterally.
age (Bar Mitzvah) of his older brother Danny, which             Volumetric measurements could not be generated with our
occurred when he was 7 years 9 months old.                      software. Therefore, a randomly selected, age-matched,
   Other mental status findings, including formal memory         normal control (who also gave informed consent to the
assessment, are presented in the section on neuro-              procedure) was scanned using the same plane and
psychological examination.                                      parameters, and the two studies were compared. The
                                                                antero-posterior length of the medial temporal grey matter
                                                                was 5 mm shorter in M.S. than in the normal control and
                                                                the vertical height of the hippocampus was markedly
Diagnostic investigations                                       diminished. These findings are apparent in Fig. 1. The
EEGs                                                            parahippocampal cortex and lateral temporal gyri were
Numerous recordings over the years showed generally             normal in thickness, and no other grey matter structure,
normal awake and sleep background activity except for an        including the entorhinal cortex, appeared abnormally small.
excessive amount of bitemporal slow activity. A left
anterior temporal spike focus was seen on four occasions.
On one occasion, a left anterior temporal electrographic        Immunological studies
seizure was recorded; this was associated with ‘the patient     Rheumatoid factor, lupus erythematosus cell preparation,
appearing scared, calling his father, and saying that           anti-nuclear antibody determination, anti-thyroid antibodies,
something or someone was after him’. On one occasion,           Coomb’s test and fungal precipitants were normal. Extensive
independent sharp wave activity was recorded from the           tests of humoral and cellular immune system functions
right anterior temporal region. On one occasion, sharply        showed no abnormalities.
contoured theta waves were present bilaterally over the
temporal regions during sleep.
                                                                Neuropsychological examination
                                                                A complete battery of neuropsychological tests was
                                                                administered in 1989, when M.S. was 27 years old. Serial
Neuro-imaging studies                                           IQ and academic test scores were available from the time
Computerized axial scan of the head without contrast was        that he was 8 years old. Additionally, memory testing was
normal. An MRI study repeated on a 0.5 Tesla scanner in         done in 1977 when he was 15 years old.
1987 showed normal T1-and T2-weighted sequences.
  MR scans were repeated on September 11, 1992 (30
years of age) and on June 9, 1994 (32 years of age). The        Intelligence
first study yielded images of relatively poorer resolution       Table 1 presents M.S’s Wechsler Intelligence Scale for
due to motion artifact. Therefore, only the findings of the      Children (WISC; Wechsler, 1949) and Wechsler Intelligence
second study will be reported. The images were generated        Scale for Children—Revised (WISC-R; Wechsler, 1974)
on a 1.5 Tesla GE Signa scanner in the sagittal plane           Verbal, Performance and Full Scale IQ scores from 1971
                                                                          Childhood onset severe anterograde amnesia               423

Table 1 Comparison of current with previous intelligence test data using Wechsler intelligence scales
                              Test date

                              Feb. 1971*         April 1972       June 1973         Nov. 1974†       June 1977           Oct. 1989‡

Age (years:months)             8:9                9:11             11:1              12:6            15                  27
Scores
  Information                                                                         8                5                  5
  Digit Span                                                                          8                7                 11
  Vocabulary                                                                          6                6                  5
  Arithmetic                                                                          8                8                  7
  Comprehension                                                                       8                7                  6
  Similarities                                                                        9                8                  7
  Picture Completion                                                                  7                8                  9
  Picture Arrangement                                                                 6               6                   8
  Block Design                                                                       17              17                  12
  Object Assembly                                                                    14              –                   10
  Digit Symbol                                                                        6                3                  4
  Verbal IQ                   115                109               94                86              80                  80
  Performance IQ              113                107              117               100              90                  91
  Full Scale IQ               115                109              l05                91              84                  83
*1971–1973,   WISC; †l974–1977, WISC-R; ‡1989, WAIS-R.

                                                                   Table 3 Comparison of current with previous academic
                                                                   achievement test scores
                                                                                             Wide Range Achievement Test (WRAT)
Table 2 Results of memory testing
                                                                                             Feb. 1971*    May 1977      Oct. 1989†
Test                       Score           Deviation in SD from
                                           expected mean (M)       Age (Years:months)        8:9           15:0           27
                                                                   Score (equivalent Grade level)‡
Wechsler Memory Scale*                                               Reading                 2M             2.8               3
  Verbal memory                51           3                        Spelling                 2M            2.5               3
  Visual memory                57           2                        Arithmetic              3E             4.2               5E
  Delayed recall               50           3                      *1971–1977,    WRAT1; †1989, WRAT-R1; ‡M       mid-year and E
Rivermead Behavioural Memory Test†                                 end of year.
  Route, immediate              0           0
  Route, delayed                3           3
  Errand, immediate             0           0                      to 1989, and subtest scores from 1974 to 1989. The recent
  Errand, delayed               3           3                      evaluation found overall intellectual functioning on the
California Verbal Learning Test
                                                                   Wechsler Adult Intelligence Scale—Revised (WAIS-R,
  Total score, trials 1–5‡     15           3
  Other conditions,†                                               1981) within the Low Average range. Comparison with
     Delayed recall, short      5           5                      previous Wechsler IQ tests indicated that his IQ declined
     Delayed recall, long       5           5                      precipitously between the ages of 8 and 12 years, and
     Recognition                5           5                      stabilized at the present, low average level, between 12
Benton Visual Retention Test*                                      and 15 years of age. Except for memory and academic
  10 s recall                  59           2                      skills, the test data presented in the following sections
  Recognition                100            0                      were collected in 1989.
Warrington Recognition Memory Test§
  Words                         4           2
  Faces                         1           3
Doors and People Test§                                             Memory
  Visual memory                 3           3                      Memory testing in 1977, when M.S. was 15 years old,
  Verbal memory                 3           3                      found deficient ( 3 SD below the normal mean) learning
  Recall memory                 3           3                      of visual designs (Benton Visual Retention Test; see Benton
  Recognition memory            3           3                      et al., 1983), free recall of a word list using a selective
  Verbal forgetting             3           2                      reminding procedure (Buschke, 1973) and verbal paired-
  Visual forgetting             4           2
                                                                   associate learning (Wechsler, 1945). In the recent testing
Scores for normative standardization sample have *M 100, SD        at 27 years of age, M.S.’s overall memory performance on
15; †M 0, SD 1; ‡M 50, SD 10; §M 10, SD 3.                         the Wechsler Memory Scale—Revised (WMS-R) (Wechsler,
424      M. Broman et al.

1987), was deficient [standard score (SS)           50].          and People Test (Baddeley et al., 1994). While performing
Performance on a second memory battery, the Rivermead            slightly above chance level, M.S. gave deficient levels of
Behavioural Memory Test (Wilson et al., 1985), was also          performance ( 2–3 SD below the normative mean) for
deficient (SS   50).                                              recognition of printed words or photos of faces (Recognition
  These and other memory test data are summarized in             Memory Test) and for recognition of printed names or
Table 2.                                                         photos of doors (Doors and People Test). The Doors and
                                                                 People Test also permits a comparison between recall and
                                                                 recognition, and between visual and verbal recognition
Verbal memory                                                    memory. The scores obtained by M.S. did not indicate a
M.S.’s short-term memory span for digits was average (six        selective advantage for either type of memory task or
forward, six in reverse; 43rd percentile, WMS-R). His            memory modality.
short-term recall of paragraphs was well below average
(second percentile) and his learning of word-pair asso-
ciates was very deficient (WMS-R)(in first percentile). He
recalled an average of 4.5 out of 25 elements from the           Language abilities
logical stories, and he acquired three out of four easy and      Basic language abilities: expressive abilities
one out of four difficult associates in six trials. After a       Rapid automatized naming (Denckla and Rudel, 1976),
30-min delay, he was able to recall the three previously         pictured-object naming (Boston Naming Test; Borad et al.,
recalled easy associates, none of the difficult word associates   1980; Kaplan et al., 1983), word fluency (Halperin et al.,
(in the first percentile), and a total of only one element        1989) and sentence repetition (Spreen and Benton, 1969),
from two stories (in the first percentile). Free recall of        were all deficient, at levels equivalent to those attained by
words (California Verbal Learning Test; Delis et al., 1987)      an average 6–11-year-old. Pictured-object naming was at
was also well below average (in the first percentile): M.S.       the expected level relative to his level of receptive
recalled eight out of 16 words in five trials, down from          vocabulary (i.e. both at the 9-year-old level). A specific
a score of nine items on the third and fourth trials. After      naming problem was not indicated.
a short, interpolated delay of 3 min, the level of his recall
dropped to one item. As in 1977, list memorizing with a
selective reminding procedure produced little increase in        Receptive language abilities
retention over trials, and the total recall score was very       Word recognition [Peabody Picture Vocabulary Test—
defective ( 4 SD) relative to normals (see Larrabee et al.,      Revised; Dunn and Dunn, 1981] was deficient at a level
1988). On a version of the Brown–Peterson interference           equivalent to the average 9-year-old; however, M.S.’s
memory task (Leng and Parkin, 1989), which requires              comprehension of sentences of varying syntactic con-
recall of individual words following 0–60 s delay intervals      struction (De Renzi and Vignolo, 1962; Menyuk et al.,
filled with a distracting activity, M.S.’s performance was        1991) and of adult logical complexity (Boston Diagnostic
within normal limits.                                            Aphasia Examination, Complex Ideational Material;
                                                                 Goodglass and Kaplan, 1983) was within the average range
                                                                 (1 SD; all measures) for an adult.
Visual memory
M.S. successfully recalled a simple errand and a simple route
immediately after these tasks were presented (Rivermead
Behavioral Memory test; Wilson et al., 1985). He forgot          Higher order language abilities
the route and the errand after a 10-min delay (in the first       M.S.’s Verbal IQ declined 35 points between his initial
percentile). His short-term memory for a visual sequence         assessment at age 8 years and the most recent assessment
(WMS-R) was low average (10%). His immediate                     when he was 27 years old. The recent Wechsler administra-
reproduction of visual designs was deficient (2–3 SD below        tion indicated deficient acquisition of factual information
average) [Revised Visual Retention Test (Benton, 1974),          and vocabulary. He was unable to state such facts as the
Complex Figure (Rey, 1964)] to low-average (WMS-R                number of weeks in a year, or to define some relatively
Visual Reproduction I: 14th percentile), depending on the        easy words such as ‘assemble’. Scores on Comprehension
measure. However, the delayed recall score was in the            and Similarities were also below-average, but his responses
first percentile for the latter test. M.S.’s impaired short-      indicated relatively stronger verbal reasoning and conceptual
term and delayed visual recall contrasted with his average       abilities compared with the level of his fund of information.
immediate recognition of visual designs (Benton, 1986).          For example, he was able to provide answers to such
                                                                 questions as ‘Why does the State require people to get a
                                                                 license before they get married?’ and he provided similarities
Recognition memory                                               to such items as ‘air-water’ (‘what you need for your
Two recognition memory tests were administered: the              body’), ‘work-play’ (‘both activities’), and ‘fly-tree’ (‘both
Warrington (1984) Recognition Memory Test and the Doors          nature, both grow’).
                                                                         Childhood onset severe anterograde amnesia           425

Academic achievement                                               was in the 16th percentile relative to adult norms (Benton
Serial academic achievement scores are presented in Table 3.       and Van Allen, 1968).



Reading and spelling                                               Visual–spatial abilities
M.S. was unable to spell well enough to write more than            M.S.’s scores on WAIS-R Block Design and Object Assembly
one incomplete sentence in response to the request to write        were average (SS of 11 and 10, respectively). The decrease
a descriptive paragraph about a picture (Test of Written           in scores compared with earlier assessments at ages 12 and
Language—Revised; Hammill and Larsen, 1988). He read               15 years (see Table 1) reflected a loss of credit due to
words in isolation at a proficiency below the third grade           slowness in completing the items. Similarly, his copy of
level (Wide Range Achievement Test—Revised; Jastak and             the Rey Complex Figure was average for accuracy and
Wilkinson, 1984). The corresponding score at 8 years old           organization. He was able to solve the adult-level Porteus
was at the mid-second grade level. Oral paragraph reading          Maze (Porteus, 1965). Map-walking performance was average
(Gray Oral Reading Test—Revised; Wiederholt and Bryant,            (Denckla et al., 1980). On the other hand, his design copying
1986) was also at first or second grade level proficiency.           skill was only equivalent to the third percentile (Visual–Motor
Silent reading comprehension (Gates–MacGinitie test,               Integration Test; Beery, 1989), due to specific difficulties in
MacGinitie and MacGinitie, 1989) was equivalent to the 1.9         reproducing overlapping perspective, correct intersection of
grade level. Spelling, like reading proficiency, was now            angles, and spatial proportion.
below the third grade level, representing no apparent change
from a score at the mid-second grade level at 8 years old.
                                                                   Executive abilities
                                                                   M.S.’s performance was slow ( 3 SD) but accurate
                                                                   ( 1 SD) on a timed target cancellation test (Sano et al.,
Arithmetic                                                         1984), and slow on tracking tests (Trailmaking Test: Part A,
M.S.’s arithmetic competence was limited to elementary
                                                                   25–50th percentile; Part B, 10th percentile) (Reitan, 1958).
addition, subtraction, multiplication and division by one unit
                                                                   M.S.’s manual speed was within the average range (25–40th
and elementary fraction concepts (e.g. he could compute 1/
                                                                   percentile; see Gardner and Broman, 1979) on the Purdue
2 but not 1/6 of a whole number). He had not mastered long
                                                                   Pegboard for his preferred right hand, left hand, both hands
division or computations involving decimals and percentages.
                                                                   together and both hands in alternation (assembly).
Arithmetic skills, now at fifth grade level, had advanced
two grade levels since the evaluations shortly after his
respiratory arrest.
                                                                   Discussion
                                                                   Comparison of M.S. with other cases of adult-
Non-language abilities                                             onset hippocampal amnesia
                                                                   The authors located five published case reports of amnesia
Non-verbal problem solving, conceptual and
                                                                   with onset in adulthood caused by documented hippocampal
analytic abilities                                                 pathology. These cases met formal DSMIII-R (American
M.S. performed in the 63rd percentile on the Progressive           Psychiatric Association, 1987) criteria for amnesic syndrome
Matrices Test (Raven et al., 1977), an untimed test of visual      documented by mental status findings or neuropsychological
pattern matching, relational thinking and analogue reasoning.      testing. Some general comments will be made about the
Logical picture arrangement was at the lower end of the            comparison between M.S. and the other cases. In four of the
average range (SS        8, WAIS-R Picture Arrangement),           five the pathology held to account for the observed memory
representing a relative improvement over his performance at        deficit was restricted to the hippocampus. These were the
age 12 years. Except for a high error rate attributable to his     cases reported by Cummings et al. (1984), by Zola-Morgan
losing track of the task from time to time due to forgetting,      et al. (R.B., 1986), by Victor and Agamanolis (1990), and
M.S.’s performance on the Wisconsin Card Sorting test (Grant       by Kartsounis et al., 1995. In the fifth case (H.M., Scoville
and Berg, 1948) was average (within 1 SD of norms matched          and Milner, 1957; Corkin, 1984), the authors attributed the
for age and education; see Heaton, 1981).                          patient’s amnesia to removal of the hippocampus, while
                                                                   acknowledging that the contribution of the amygdala could
                                                                   not be entirely ruled out, because the operation that resulted
Visual–perceptual abilities                                        in amnesia always involved removal of the hippocampus
M.S.’s picture recognition was average (WAIS-R Picture             together with the uncus and amygdala. From the description
Completion, SS     9), representing a relative improvement         of the operation, it is likely that the excision involved the
since assessment at age 12 years. His ability to match             perirhinal cortex. On the other hand, R.B.’s pathology is
photographs of faces in differing orientations to a target face,   held to be restricted to the CA1 area of the hippocampus,
426      M. Broman et al.

representing the most specific human data on the anatomy               on autobiographical and objective tests, indicating amnesia
of amnesia thus far.                                                  extending back 11 years before his operation (Corkin, 1984).
   In two cases, H.M. and R.B., there is extensive                       H.M. is unique in that extensive testing was done of
neuropsychological documentation not only of the memory               perceptual-motor and other abilities now labelled ‘procedural
deficits but also of other, non-mnemonic cognitive functions.          memory’. H.M. demonstrated skill-learning approximating
In the cases presented by Victor and Agamanolis (1990) and            that of normal subjects on such tests as rotary pursuit learning,
by Cummings et al. (1984), the data with respect to memory            mirror reading, repetition priming and a problem-solving test
and cognitive functions were gathered in the course of mental         (Tower of Hanoi; Corkin, 1984).
status examinations. Little or no formal psychological testing           In the sections that follow, the results of neuro-
was done.                                                             psychological testing with M.S. in the light of the data
   In virtually all cases, language and non-language cognitive        summarized above for hippocampal amnesia cases originating
abilities were judged to be mostly intact, ‘within normal             in adulthood will be discussed.
limits’ or with average or better scores in comparison with
normal standards. The amnesics presented by Cummings
et al. (1984) and Victor and Agamanolis (1990) were said              Memory
to have good or excellent comprehension and expressive                By objective test criteria, M.S.’s memory impairment is as
language. Where IQ testing was done, in the cases presented           severe as H.M.’s and more severe than the other adult
by Kartsounis et al. (1995), by Corkin (1984) and by Zola-            hippocampal amnesics. Like H.M., M.S.’s immediate auditory
Morgan et al. (1986) verbal subtest scores were, on the               memory span is normal (and curiously in his case, seems to
whole, average or better.                                             have increased over the years) while short-term recall of
   When naming was formally tested (H.M., R.B.) it was                new information exceeding his immediate span is severely
found to be normal. However, H.M. demonstrated slight                 impaired. The extent of medial temporal lobe destruction
deficits of sentence repetition, spelling and word fluency and          was much more extensive in H.M. (resection of the temporal
he was found to be slightly anomic.                                   pole, amygdaloid complex and two-thirds of the rostro-caudal
   Documentation of non-language cognitive abilities was              extent of the hippocampal formation) than in M.S. However,
scanty among the five cases. Wechsler Performance Scale                the degree of M.S.’s memory impairment is similarly
subtests scores were average or better for the three cases for        profound (again, by test criteria) supporting the critical role
whom those data are available (H.M., R.B., and the case of            of the hippocampus in long-term memory formation. In the
Kartsounis et al., 1995). Victor and Agamanolis (1990) did            case of H.M. the relative contribution of the removal of the
not collect configurational data, whereas Cummings et al.              amygdala and the hippocampus was unclear, since both were
(1984) found normal 3D copying and map drawing abilities              completely resected bilaterally. The present case, which
in their amnesic patient. R.B. demonstrated normal                    shows marked bilateral atrophy of the hippocampus alone
functioning on all but one test in a so-called parietal lobe          without any MRI evidence of amygdalar atrophy, supports
battery       (not    further     specified).      The     detailed    the anatomical evidence provided by cases R.B. and the case
neuropsychological data collected on H.M. found excellent             reported by Victor and Agamanolis (1990), i.e. that the
abilities on most visual-spatial and constructional tests, the        amygdala does not play a major role in anterograde memory.
exceptions being his poor performances on hidden figures                  Evidence from early monkey studies (Mishkin, 1978)
and maze learning.                                                    suggested that removal of the amygdala, in addition to the
   Documentation of executive and other abilities associated          destruction of the hippocampi, increased memory deficit.
with frontal lobe functioning relied on a different array of          Subsequent studies (Squire, 1992) showed that selective
tests and measures in each case, so that comparison among             stereotactic lesions of the amygdala alone did not cause
the five with respect to abilities in this category can be             impairment of memory. In contrast, monkeys with bilateral
accomplished only superficially. H.M. alone had formal                 lesions of the hippocampus and of the perirhinal and
testing in this category and was found to demonstrate excellent       entorhinal cortex (H       lesion) had more severe memory
cognitive flexibility with respect to card sorting (Wisconsin          deficit than those with hippocampal lesions alone. It was
Card Sorting Test). The cases with no formal testing                  concluded that it was the cortical damage associated with
(Cummings et al., 1984; Victor and Agamanolis, 1990)                  resection of the amygdala that was responsible for the
exhibited signs of frontal lobe dysfunction (confabulation,           exacerbation of memory impairment from damage to the
irritability, apathy and lack of social initiative). Formal testing   hippocampal formation.
in this category was not done in the case of R.B. Retrograde             M.S.’s short-term recall of visual material is slightly less
amnesia for biographical information was demonstrated by              impaired compared with short-term verbal recall. His delayed
the cases of Victor and Agamanolis (1990), Kartsounis et al.          recall on formal testing is almost nonexistent. (Whereas,
(1995) and Cummings et al. (1984). Of the five cases, only             according to our observations, he does retain certain
R.B. did not demonstrate retrograde amnesia. His recall was           information to which he has been repeatedly exposed, such
normal on objective tests of remote memory (famous faces,             as the names of characters and theme songs from favourite
events and TV shows). H.M. demonstrated retrograde amnesia            television programs, and certain personal information, such
                                                                          Childhood onset severe anterograde amnesia           427

as his address, phone number and certain data from his              memories were acquired during the narrow time window of
personal history.)                                                  ~6 months prior to his anoxic episode. These were memories
   Recognition memory was not spared in M.S. His                    of people, faces names and places, some of which he was
performance was equally impaired on recall and recognition          able to reproduce with surprising accuracy. It is of interest
memory tests. The method of testing recognition memory              that he had absolutely no memories of his brother’s Bar
can influence results of testing with amnesic patients: Freed        Mitzvah which occurred when he was 7 years, 9 months. In
and Corkin (1988) reported normal recognition memory in             American Jewish culture this is a major religious and social
H.M. for picture stimuli when extra study time and a delayed        event, and it was celebrated by M.S.’s parents with a party
nonmatching-to-sample procedure was used (patient says              of 125 guests. There were no retained memories of any kind
‘yes’ to stimuli he judges to be unfamiliar). Recognition           dating to 6–9 months prior to the anoxia. It is impossible
memory measures with M.S. employed a forced-choice                  to determine at this time whether his store of retrograde
procedure (patient choosing the stimuli he had seen before          memories has diminished with the passage of time.
from an array containing the target and one or more distractor         M.S.’s ability to recall memories from the 6-month period
stimuli). R.B. also demonstrated deficient recognition               prior to the onset of amnesia, and his forgetting of older
memory on tests not using a delayed nonmatching-to-sample           memories, represents a finding that is the converse of the
response format. However, in the case of M.S., recognition          pattern in adult amnesia. The adult hippocampal amnesics
memory was slightly better than chance level.                       cited above had forgotten events that occurred during some
   The severity of M.S.’s free recall and recognition memory        time interval immediately preceding the onset of amnesia;
deficits suggests that perhaps, in addition to the destruction of    whereas older memories were better retained. This is the
the hippocampal formation, wider cortical damage involving          pattern (or ‘temporal gradient’) that is typically seen in
either the entorhinal, perirhinal or parahippocampal cortex         retrograde amnesia of other aetiologies, for example, alcoholic
may have occurred. Aggleton and Shaw (1996), after a re-            Korsakoff’s syndrome (Butters and Stuss, 1989).
analysis of published cases of anterograde amnesia, reported           However, considerable variability in the pattern of
that cases exhibiting impairments of both anterograde recall        retrograde amnesia has been reported. Sometimes the
and recognition memory on the Warrington Recognition                temporal gradient may be absent i.e. there is no sparing of
Memory Test, had more diffuse lesions compared with cases           remote memories (Sanders and Warrington, 1971) or
who exhibited normal Recognition Memory Test                        retrograde amnesia may be entirely absent as in case R.B.
performance. In the latter group of cases, the lesion was           However, more extensive damage to the hippocampal
restricted to the hippocampal formation, fornix or                  formation was associated with greater retrograde amnesia
diencephalon. Although, in our case, only selective atrophy         among three cases reported by Rempel-Clower et al. (1996).
of the hippocampus was demonstrated by special MRI study,           Retrograde amnesia was thought to be present in one
it is generally accepted that focal ischaemic lesions may           childhood case (C.C.; Ostergaard, 1987). Due to the difficulty
occur as a result of respiratory arrest, which are below the        of establishing the presence of remote memories in a child,
resolving power of MRI technique.                                   Ostergaard developed an ingenious but indirect method of
   On the other hand, Rempel-Clower et al. (1996) reported          measuring learning acquired early in life. He asked the
that recognition memory and recall were both impaired               subject to classify words acquired at various ages in childhood
in three adult amnesia cases with damage limited to the             as ‘Living’ or ‘Non- Living’ and measured the reaction-
hippocampal formation. The recognition measure employed             times. In C.C.’s case the latencies of responses for words
was a modified version of the Warrington Recognition                 acquired in early childhood were much shorter than those
Memory Test. The study supports the idea that hippocampal           acquired close to the onset of amnesia.
lesions impair recognition as much as recall. Although the
study involved post-mortem examination of brain tissue, the
possibility exists that covert damage could have occurred           Language abilities
that extended beyond the hippocampus.                               M.S.’s steady decline in IQ between ages 8 and 15 years
   M.S.’s immediate recall is not derailed by interpolated          reflected a relatively greater decline in relative performance
activity. His recall productions do not contain confabulations.     on verbal compared with performance IQ subtests. The
He does not perseverate, and his abilities to track, organize,      increasing lag in verbal proficiency appears to reflect a
plan and shift mental set are strong. In short, he does not         cessation during that period of development, predominantly
demonstrate either radiological or cognitive evidence of            of factual information, vocabulary and, perhaps, of the
frontal lobe pathology. In comparison, two adult hippocampal        knowledge and skills required to solve oral arithmetic
amnesia cases did show behavioural signs suggestive of              problems. The fact that the Verbal IQ remained stable between
frontal lobe impairment: these were the case reported by            ages 15 and 27 years (see Table 1) suggests that there has
Victor and Agamanolis (1990; apathy, irritability, short            been some increment of semantic knowledge and verbal
temper, and failure to initiate activities) and the case reported   conceptual development, a finding characteristic of H.M.
by Cummings et al. (1984; confabulation).                           (Corkin, 1984) and R.B. (Zola-Morgan et al., 1986). The
   It is apparent that M.S.’s only remaining retrograde             only two data points for which raw scores are available on
428      M. Broman et al.

the same instrument (the WISC-R), ages 12 and 15 years,            no interference with either basic visual–perceptual processing
indicated slight, one- or two-point increments on Verbal           abilities or visual–perceptual conceptual development.
Scale subtests.                                                    Comparison of the most recent Wechsler scores with earlier
   In his most recent assessment, the level of sophistication      ones indicated a decline, after adolescence, in the rate
of M.S.’s verbal and language skills was strikingly variable.      (speed) of spatial-constructional problem-solving, represented
Reading and spelling appeared to have been arrested at the         by block design and object assembly.
very level of his attainment at the time of onset of his amnesic      M.S.’s logical problem-solving ability tested with visual
disorder (second grade). Other basic language abilities were       examples in an untimed format (Raven test) is somewhat
also developed to 6- or 7-year-old proficiency (word fluency,        above-average, again suggesting that the development of his
sentence repetition), while other language abilities were          logical skills was not markedly affected by his amnesic
somewhat more advanced (9-year-old level: vocabulary               disorder. That learning to reason logically can develop
recognition). Other conceptual language abilities have             independently of the memory system that supports the
developed to an adult level, including logical comprehension       acquisition of facts and information is not self-evident, but
of oral paragraphs and sentences. Written mathematical             it does appear to occur according to the data presented by
abilities have developed to the fifth grade level, intermediate     M.S.’s case.
between the arrested level of development of literacy skills          M. S.’s slow performances on clerical tasks, such as target
and the adult level of verbal and nonverbal logical skills.        cancellation and trail-making, and the loss of speed on
                                                                   constructional tasks appear to indicate a decline in
                                                                   information-processing speed. The basis for this finding is
Amnesia versus anomia                                              unclear, but may relate to his anticonvulsant medication.
The deficits of vocabulary development, rapid automatized           Slow response times contributed to a significant portion of
naming, word fluency and sentence repetition suggest possible       the decline in Performance IQ from age 8 years to the recent
damage to temporal lobe neocortical language systems.              assessment.
Although his MRI showed tissue loss limited to the
hippocampus, it is possible that a wider area of the left
temporal cortex could have sustained microscopic
pathological changes due to anoxia without demonstrable            Comparison of M.S. with other cases of
changes on imaging. A similar pattern of language                  childhood-onset amnesia
impairments (spelling, fluency and repetition) was exhibited        One well-documented and extensively studied case of
by H.M. Naming deficits that are independent of memory              childhood onset amnesia was a 10-year-old boy (C.C.) who
impairment have been described for children and adults with        developed cerebral oedema and became comatose due to
temporal lobe epilepsy (Mayeux et al., 1980; Broman, 1993).        water intoxication in the course of treatment of diabetic keto-
A pattern of concurrent language and memory deficits is             acidosis (Ostergaard, 1987). Thirty hours after the onset of
seen in other childhood–onset amnesia cases, described below.      symptoms, he had a right-sided convulsion with secondary
   M.S.’s language deficits raise the issue of whether his          generalization and respiratory arrest. A CT scan at that time
verbal memory disorder represents true amnesia. His complete       was consistent with a large left temporal-parietal infarct and
failure to recall any information after a delay, including         with uncal herniation. He recovered normal neurological
material well within his language competence, is not reducible     function over a period of several months except for severe
to a language disorder. However, the differentiation of            impairment of recent memory and occasional seizures. A
language from verbal memory deficits and the corresponding          follow-up CT scan showed decreased attenuation of the left
differentiation of hippocampal from temporal neocortical           medial temporal and occipital lobes which involved the entire
contribution to verbal amnesia is difficult at best, a point        hippocampus, the parahippocampal gyrus and part of the
made by Smith (1989) in her discussion of temporal                 paraventricular area, extending into the temporal–occipital
lobectomy patients. Suffice to say that in the present case,        junction and into the infra-calcarine region. On the right side,
the profundity of the amnesic deficit that encompasses verbal       there was a small area of decreased attenuation involving the
and visual information and the MRI, which shows severe             most anterior portion of the hippocampus and the
hippocampal atrophy, leave no doubt about the existence of         parahippocampal gyrus. Thus, it seems well documented that
a true hippocampal amnesia.                                        this patient suffered severe left hippocampal damage with at
                                                                   least partial right hippocampal involvement. On testing at
                                                                   the age of 15 years, he showed significant impairment of
Configurational abilities                                           certain semantic language and verbal memory abilities and
The majority of M.S.’s visual–perceptual and visual–spatial        preservation of certain procedural memory skills. His reading
abilities are average or better, including complex figure           age, spelling age and reading comprehension were about 3.5
copying, map walking, pictorial recognition, block design          years behind his chronological age, but, unlike M.S., he had
reproduction, puzzle assembly, visual pattern matching and         made some modest progress in these areas since his acute
face matching. M.S.’s amnesic disorder resulted in little or       illness. His mathematical skills progressed modestly, but
                                                                                     Childhood onset severe anterograde amnesia            429

more than the above-mentioned semantic verbal skills over                      childhood amnesia in an abstract form. Their case, J.F.,
a 5-year period. Like M.S., his procedural learning and                        developed seizures at the age of 4 years and a memory
procedural memory tested by two tasks was normal. The                          problem was recognized at the age of 8 years as a result of
milder language and academic impairments in this patient                       learning difficulties at school. MRI showed bilateral mesial
might be explained by his less severe degree of amnesia,                       temporal sclerosis and intact mamillary bodies. Their second
perhaps due to partial sparing of the right hippocampal                        case, J.L., underwent surgery for a craniopharyngioma at the
formation.                                                                     age of 12 years, and developed anterograde amnesia post-
   The only other published report of acquired childhood                       operatively. In this case, MRI showed periventricular
amnesia, by Wood et al. (1989), is problematic because this                    diencephalic pathology encompassing the mamillary bodies.
patient appeared to have suffered a severe global cerebral                     At the age of 13 years, both patients were impaired for tests
injury without a definite aetiology. They described a 9-year-                   of declarative memory, whereas their performance on tasks
old girl (T.C.) who suffered a severe encephalopathic episode                  of procedural memory was normal.
which was thought to be consistent with herpes simplex                            Another case reported by Vargha-Khadem et al. (1994)
encephalitis. The reported details of her clinical course were                 exhibited amnesia, alexia and agnosia beginning at age 13
scanty and there were no reported neuro-imaging studies                        years. It is difficult to relate the patient’s unique amnesic
during the acute illness. She had a biphasic clinical course                   syndrome to a specific aetiology or anatomical defect, due
followed by generalized impairment of all neurological                         to the complexity of neuropathology revealed by imaging
functions (motor, language and self-care abilities).                           studies and treatments. Because of the later age of onset of
   One year after the onset, her IQ was below 50. Two years                    amnesia, in adolescence, and the relatively short duration of
after onset, her physical recovery was complete, but her                       neuropsychological followup (3 years), the authors’
memory was severely impaired. Seven years after onset, at                      discussion of the case does not contribute to the issues
the age of 16 years, she obtained a Verbal IQ of 78,                           (pertaining to childhood onset and long term sequelae) that
Performance IQ of 91 and Full Scale IQ of 83, and she had                      we have addressed in the present report.
a severe memory deficit. The major point made by the authors                       Differences in the neuropsychological findings among the
was that despite the severe anterograde memory loss, T.C.                      four cases of amnesia with onset in childhood (age 12 years
was able to continue learning in the domain of declarative                     or younger) with documented brain pathology reported thus
memory. Unfortunately, the value of these conclusions is                       far might be explained by differences in the severity of the
diminished by the absence of neuro-anatomical localization                     memory impairment in relation to overall IQ, in the type and
of her lesions.                                                                location of brain pathology, the length of follow-up and
   Vargha-Khadem et al. (1992) have reported two cases of                      possible effects of anticonvulsant therapy. These relationships

Table 4A Paediatric cases: clinical data
Case           Etiology                       Imaging data                             Onset age             Follow-up              Seizures
                                                                                       (years)               (years)

M.S.           Seizure→respiratory            MRI: bilateral                            7                    20                     Yes
               arrest→anoxia                  hippocampal atrophy

C.C.           Seizure→respiratory            CT: left medial temporal-                10                     4.5                   Yes
               arrest→anoxia                  occipital attenuation

J.L.           Craniopharyngioma              Ventral diencephalon incl.               12                     1                     Unknown
                                              mammillary bodies

J.F.           Seizures                       Bilateral mesial TL sclerosis/            4                    10                     Yes
                                              hippocampal atrophy


Table 4B Paediatric cases: test scores
Case     Wechsler IQ                              Wechsler Memory Quotient                         Academic scores

         Verbal     Performance      Full scale   Immediate                Delayed                 Reading           Spelling       Arithmetic

M.S.      80         89               82            50                         50                  Second grade      Second grade   Fifth grade
C.C.      99         94               96             1 SD from M*               0 items recalled   11.8 AE†          10.8 AE        –
J.L.      81         96               87            64                     –                       12.6 AE‡          –              –
J.F.      96        117              105            84                     –                       10.5 AE‡          9.0 AE         10.5 AE

AE     age equivalent (years). *Logical memory subtest only, within 1 SD of mean (M); †Schonell test; ‡test unreported.
430      M. Broman et al.

are detailed in Table 4. Those cases having documented             cases. Still, the further distinction of those types of semantic
damage to the hippocampus and/or mesial temporal region            learning that are still possible with hippocampal destruction,
[C.C. (Ostergaard, 1987); M.S. and J.F. (Vargha-Khadem             while possible in adult patients (namely, the distinction
et al., 1992)] appear to have sustained some degree of             between the learning of facts and the learning of grammar-
slowing in the development of verbal abilities and reading         like rules; see Squire and Knowlton, 1995), is dramatically
decoding skills. The lesser degree of reading and spelling         highlighted by the results of examination of the language
impairment in C.C. and J.F. compared with M.S. could be            abilities of patients who became amnesic in childhood, and
related to the relatively shorter length of follow-up, and/or      probably can be systematically and fully elucidated only in
the lesser degree of documented memory impairment. By              the context of developmental amnesia cases.
contrast, J.L. (Vargha-Khadem et al., 1992), who had damage
to the ventral diencephalon and mamillary bodies, was reading
at the expected level with reference to his chronological age.     Declarative versus procedural memory
                                                                   Testing of so-called procedural skills yielded average or
                                                                   better scores for C.C. (Gollin Incomplete Pictures, and a
Implications for theories of memory, learning                      computer game), as well as for the two cases reported by
and development                                                    Vargha- Khadem et al. (1992, mirror-tracing). Logical
There are two types of questions raised by the case of M.S.        thinking skill, an ability that developed normally in M.S.,
One is, what are the implications for a theory of memory?          could represent another function of the procedural learning
A second is, what are the implications for a theory of             system that is spared in amnesia (Squire, 1992). Adult
development?                                                       amnesic patients have been shown to perform normally on
                                                                   such logical tasks as classification of dot patterns (Kolodny,
                                                                   1994) and card sorting by rules demanding spatial or visual
Implications for a theory of memory                                analysis (Delis et al., 1992). Reading does not seem to fit
The previous case reports of childhood onset amnesia               neatly either in the declarative–procedural or in the episodic–
presented the opportunity to test certain hypotheses about         semantic dichotomy: it seems to have aspects both of a
the organization of memory that have emanated from adult           semantic (processing and/or learning) and a procedural ability,
case studies. In particular, the validity of the episodic versus   a point made by Ostergaard and Squire (1990).
semantic memory (Tulving, 1972; Kinsbourne and Wood,
1982) and the declarative versus procedural memory (Cohen,
1984; Squire, 1987) dichotomies for describing human               Implications for theories of learning and
memory systems were examined in the context of the data            development
provided by the childhood onset cases.                             Exploration of the consequences of hippocampal damage for
                                                                   human memory and cognition can be done with adult
                                                                   hippocampal patients, but the consequences of hippocampal
Episodic versus semantic memory                                    damage for development of those functions can only be
Tulving has defined semantic memory both in a narrower              studied with developmental cases, cases of amnesia in which
sense, as memory that pertains to words and concepts and           the onset occurred in childhood. M.S. is the first report of a
the rules pertaining to their usage (Tulving, 1972) and in a       patient with amnesia originating in childhood to demonstrate
broader sense, as memory that pertains to knowledge that is        a dissociation between impaired memory and skill at logical
not specifically tied to language or to meaning (Tulving,           problem-solving. That is, his case is the first to suggest that
1995). The data presented by M.S. and C.C. are consistent          logical problem-solving ability can develop nearly normally
with the argument that one aspect of semantic memory,              in spite of severe amnesia. Learning of verbal facts, in
vocabulary development, was affected by hippocampal                contrast, does appear to require intact long term (declarative)
damage, whereas other language skills, including grammatical       memory capability.
and verbal–logical comprehension, were relatively spared.             The implication of this finding is that at least one major
However, it may be more accurate to state that semantic            cognitive function develops without the contribution of long-
learning was affected, rather than semantic memory.                term memory. Cognitive and academic skills can be regarded
    Tulving (1995) recently acknowledged the validity of a         as having three conceptually separate components: a
distinction between semantic memory acquisition, i.e.              procedural (skill-based) component, a declarative (fact-
learning, and semantic memory retrieval; this is illustrated       learning) component and a perceptual (encoding) component
by the fact that H.M. can recall semantic (factual) information    (Wagner and Torgesen, 1987). Education and remedial work
learned before the onset of his amnesia, while he demonstrates     must address all three components: the learning of procedures,
little acquisition of new information. Seen over the course        the memorizing of facts and the encoding of information so
of development, the deficit of semantic learning has obvious,       that it is accessible to memorizing (Nelson and Warrington,
devastating consequences not apparent in the adult amnesia         1980) or procedural operations (Lovett et al., 1994).
                                                                            Childhood onset severe anterograde amnesia             431

   For example, both reading and mathematics rely on the              Benton AL. The Revised Visual Retention Test 4th ed. New York:
abilities to encode language and number information and               Psychological Corporation, 1974.
to memorize ‘facts’ (tables, grammar, spelling patterns).             Benton AL. Der Benton Test. Bern (Switzerland): Verlag Hans
Mathematics additionally requires the ability to employ logic         Huber, 1986.
in the solution of problems (Garnett and Fleischner, 1987).
                                                                      Benton AL, Van Allen MW. Impairment in facial recognition in
Learning-disabled individuals can be deficient in any one or
                                                                      patients with cerebral disease. Trans Am Neurol Assoc 1968; 93:
more of these learning components, and different remedial             38–42.
approaches are needed in each case.
                                                                      Benton AL, Hamsher KDeS, Varney NR, Spreen O. Contributions
                                                                      to neuropsychological assessment. New York: Oxford University
                                                                      Press, 1983.
Conclusions
   We have described a case of severe anterograde memory              Borad JC, Goodglass H, Kaplan, E. Normative data on the Boston
disorder with onset in childhood. The location of the lesion          Diagnostic Aphasia Examination, Parietal Lobe Battery, and the
and neuropsychological pattern replicate many of the features         Boston Naming Test. J Clin Neuropsychol 1980; 2: 209–15.
of adult hippocampal amnesia. The MRI results indicated a             Broman M. Language and memory in children with combined
lesion restricted to the hippocampus, but the anoxic aetiology        complex-partial epilepsy and reading disorder. Ann NY Acad Sci
of the lesion would not rule out damage extending to                  1993; 682: 323–5.
surrounding cortex. The case of M.S. adds to our limited              Buschke H. Selective reminding for analysis of memory and
documentation about the role of long- term memory in the              learning. J Verb Learn Verb Behav 1973; 12: 543–50.
growth of cognitive abilities during childhood. The price of
his amnesia was a disruption of acquisition of facts and              Butters N, Stuss DT. Diencephalic amnesia. In: Boller F, Grafman
                                                                      J, editors. Handbook of Neuropsychology, Vol. 3. Amsterdam:
vocabulary, while development of grammatical and logical
                                                                      Elsevier, 1989: 107–48.
comprehension was spared. The growth of logic included the
abilities to reason by analogy, to detect verbal absurdities          Christ A. The elusive neuropsychiatric symptoms. In: Christ AE,
and to learn mathematical operations, although to a more              Flomenhaft K, editors. Childhood cancer: impact on the family.
limited extent. The notion that a severe anterograde memory           New York: Plenum Press, 1984: 217–46.
disorder of relatively early onset necessarily causes a               Cohen NJ. Preserved learning capacity in amnesia: evidence for
nonspecific or global impairment of learning, cognition and            multiple memory systems. In: Squire LR, Butters N, editors.
cognitive development was not supported by the long-term              Neuropsychology of memory. New York: Guilford press, 1984:
neuropsychological outcome in this case.                              83–103.
                                                                      Corkin S. Lasting consequences of bilateral medial temporal
                                                                      lobectomy: clinical course and experimental findings in H.M. Semin
Acknowledgements                                                      Neurol 1984; 4: 249–259.
We wish to thank Dr Adolph Christ who referred this patient,
                                                                      Cummings JL, Tomiyasu U, Reed S, Benson DF. Amnesia with
Drs Mark Press, Michele Shackelford and Paul Berger-Gross             hippocampal lesions after cardiopulmonary arrest. Neurology 1984;
who performed psychological examinations and Dr Siriwan               34: 679–81.
Kriengkrairut who assisted with the literature search. We
also thank Mrs Rose Babb for producing the tables and Dr              Damasio AR, Tranel D, Damasio H. Amnesia caused by herpes
                                                                      simplex encephalitis infarctions in basal forebrain, Alzheimer’s
William Winter for his helpful discussions during his work
                                                                      disease and anoxia/ischemia. In: Boller F, Grafman J, editors.
with M.S., and Drs John Kubie and Carolyn Rovee-Collier
                                                                      Handbook of neuropsychology, Vol. 3. Amsterdam: Elsevier, 1989:
who made helpful comments about earlier versions of this              49–66.
manuscript.
                                                                      Delis DC, Kramer JH, Kaplan E, Ober BA. CVLT: California Verbal
                                                                      Learning Test. San Antonio: Psychological Corporation, 1987.
References                                                            Delis DC, Squire LR, Bihrle A, Massman P. Componential analysis
Aggleton JP, Shaw C. Amnesia and recognition memory: a reanalysis     of problem-solving ability: performance of patients with frontal
of psychometric data. Neuropsychologia 1996; 34: 51–62.               lobe damage and amnesic patients on a new sorting test.
                                                                      Neuropsychologia 1992; 30: 683–97.
American Psychiatric Association. Diagnostic and statistical manual
of mental disorders. 3rd edition-revised. Washington (DC): American   Denckla MB. Development of motor co-ordination in normal
Psychiatric Association, 1987.                                        children. Dev Med Child Neurol 1974; 16: 729–41.
Baddeley A, Emslie H, Nimmo-Smith I. Doors and People Manual.         Denckla MB, Rudel, RG. Rapid ‘automatized’ naming (R.A.N.):
Bury St Edmunds, (England): Thames Valley Test Company, 1994.         dyslexia differentiated from other learning disabilities.
                                                                      Neuropsychologia 1976; 14: 471–9.
Beery KM. The VMI developmental test of visual-motor integration:
administration, scoring and teaching manual. 3rd rev. Cleveland:      Denckla MB, Rudel RG, Broman M. The development of a spatial
Modern Curriculum Press, 1989.                                        orientation skill in normal, learning-disabled, and neurologically
432       M. Broman et al.

impaired children. In: Caplan D, editor. Biological studies of mental   Mayeux R, Brandt J, Rosen J, Benson DF. Interictal memory and
processes. Cambridge (MA): MIT Press, 1980: 44–59.                      language impairment in temporal lobe epilepsy. Neurology 1980;
                                                                        30: 120–5.
De Renzi E, Vignolo LA. The Token Test: a sensitive test to detect
receptive disturbances in aphasics. Brain 1962; 85: 665–78.             Menyuk P, Chesnick M, Liebergott JW, Korngold B, D’Agostino
                                                                        R, Belanger A. Predicting reading problems in at-risk children. J
Dunn LM, Dunn LM. Peabody Picture Vocabulary Test-Revised.
                                                                        Speech Hear Res 1991; 34: 893–903.
Circle Pines (Minnesota): American Guidance Service, 1981.
                                                                        Mishkin M. Memory in monkeys severely impaired by combined
Freed DM, Corkin S. Rate of forgetting in H.M.: 6-month
                                                                        but not by separate removal of amygdala and hippocampus. Nature
recognition. Behav Neurosci 1988; 102: 823–7.
                                                                        1978; 273: 297–8.
Gardner RA, Broman M. The Purdue Pegboard: normative data on
                                                                        Nelson HE, Warrington, EK. An investigation of memory functions
1334 school children, J Clin Child Psychol 1979; 8: 156–62.
                                                                        in dyslexic children. Br J Psychol 1980; 71: 487–503.
Garnett K, Fleischner J. Mathematical disabilities. Pediatr Ann
                                                                        Ostergaard AL. Episodic, semantic and procedural memory in a
1987; 16: 159–76.
                                                                        case of amnesia at an early age. Neuropsychologia 1987; 25: 341–57.
Goodglass H, Kaplan E. Boston Diagnostic Aphasia Examination
                                                                        Ostergaard A, Squire LR. Childhood amnesia and distinctions
Booklet. Philadelphia: Lea and Febiger, 1983.
                                                                        between forms of memory: a comment on Wood, Brown, and
Grant DA, Berg EA. A behavioral analysis of degree of                   Felton. Brain Cogn 1990; 14: 127–33.
reinforcement and ease of shifting to new responses in a Weigl-
                                                                        Porteus SD. Porteus Maze Test. Palo Alto (CA): Pacific Books, 1965.
type card-sorting problem. J Exp Psychol 1948; 38: 404–11.
                                                                        Raven JC, Court JH, Raven J. Manual for Raven’s Progressive
Halperin JM, Healey JM, Zeitchik E, Ludman WL, Weinstein L.
                                                                        Matrices and Vocabulary Scales. London: H.K.Lewis, 1977.
Developmental aspects of linguistic and mnestic abilities in normal
children. J Clin Exp Neuropsychol 1989; 11: 518–28.                     Reitan RM. Validity of the Trail Making Test as an indicator of
                                                                        organic brain damage. Percept Mot Skills 1958; 8: 271–6.
Hammill DD, Larsen SC. TOWL-2: Test of Written Language-2.
Austin (TX): Pro-Ed, 1988.                                              Rempel-Clower NL, Zola SM, Squire LR, Amarl DG. Three cases
                                                                        of enduring memory impairment after bilateral damage limited to
Heaton R. Wisconsin Card Sorting Test-manual. Odessa (FL):
                                                                        the hippocampal formation. J Neurosci 1996; 16: 5233–55.
Psychological Assessment Resources, 1981.
                                                                        Rey A. L’examen clinique en psychologie. Paris: Presses
Jastak S, Wilkinson GS. Wide Range Achievement Test-Revised.
                                                                        Universitaire de France, 1964.
Wilmington (DE): Jastak Assessment Systems, 1984.
                                                                        Sanders HI, Warrington EK. Memory for remote events in amnesic
Kaplan E, Goodglass H, Weintraub S. Boston Naming Test.
                                                                        patients. Brain 1971; 94: 661–8.
Philadelphia: Lea and Febiger, 1983.
                                                                        Sano M, Rosen W, Mayeux R. Attention deficits in Alzheimer’s
Kartsounis LD, Rudge P, Stevens JM. Bilateral lesions of the CA1
                                                                        disease. Annual Meeting of the American Psychological Association,
and CA2 fields of the hippocampus are sufficient to cause a severe
                                                                        Toronto: August, 1984.
amnesic syndrome in humans. J Neurol Neurosurg Psychiatry 1995;
59: 95–8.                                                               Scoville WB, Milner B. Loss of recent memory after bilateral
                                                                        hippocampal lesions. J Neurol Neurosurg Psychiatry 1957; 20:
Kinsbourne M, Wood F. Theoretical considerations regarding the
                                                                        11–21.
episodic–semantic memory distinction. In: Cermak LS, editor.
Human memory and amnesia. Hillsdale (NJ): Lawrence Erlbaum,             Shimamura AP. Disorders of memory: the cognitive science
1982: 195–217.                                                          perspective. In: Boller F, Grafman J, editors. Handbook of
                                                                        neuropsychology, Vol. 3. Amsterdam: Elsevier, 1989: 35–74.
Kolodny JA. Memory processes in classification learning: an
investigation of amnesic performance in categorization of dot           Smith ML. Memory disorders associated with temporal lobe lesions.
patterns and artistic styles. Psychol Sci 1994; 5: 164–9.               In: Boller F, Grafman J, editors. Handbook of neuropsychology,
                                                                        Vol. 3. Amsterdam: Elsevier, 1989: 91–106.
Larrabee GJ, Trahan DE, Curtiss G, Levin HS. Normative data for
the verbal selective reminding test. Neuropsychology 1988; 2:           Spreen O, Benton AL. Neurosensory Center Comprehensive
173–82.                                                                 Examination for Aphasia. Victoria (BC): Neuropsychological
                                                                        Laboratory, Dept of Psychology, University of Victoria, 1969.
Leng NR, Parkin AJ. Aetiological variation in the amnesic syndrome:
comparisons using the Brown-Peterson task. Cortex 1989; 25: 251–9.      Squire LR. Memory and brain. New York: Oxford University
                                                                        Press, 1987.
Lovett MW, Borden SL, DeLuca T, Lacerenza L, Benson NJ, and
Blackstone D. Treating the core deficits of developmental dyslexia:      Squire LR. Memory and the hippocampus: a synthesis from findings
evidence of transfer of learning after phonologically- and strategy-    with rats, monkeys and humans [published erratum appears in
based reading training programs. Dev Psychol 1994; 30: 805–22.          Psychol Rev 1992; 99: 582]. Psychol Rev 1992; 99: 195–231.
MacGinitie WH, MacGinitie RK. Gates-McGinitie Reading Tests:            Squire LR, Knowlton BJ. Memory, hippocampus and brain systems.
manual for scoring and interpretation. Chicago: Riverside               In: Gazzaniga MS, editor. The cognitive neurosciences. Cambridge
Publishing, 1989.                                                       (MA): MIT Press, 1995: 825–37.
                                                                                Childhood onset severe anterograde amnesia              433

Tulving E. Episodic and semantic memory. In: Tulving E, Donaldson        Wechsler D. Manual for the Wechsler Intelligence Scale for Children.
W, editors. Organization of memory. New York: Academic Press,            New York: Psychological Corporation, 1949.
1972: 381–403.
                                                                         Wechsler D. Manual for the Wechsler Intelligence Scale for Children-
Tulving E. Organization of memory: quo vadis? In: Gazzaniga MS,          Revised. San Antonio (TX): Psychological Corporation, 1974.
editor. The cognitive neurosciences. Cambridge (MA): MIT Press,          Wechsler D. WAIS-R Manual: Wechsler Adult Intelligence Scale-
1995: 839–47.                                                            Revised. San Antonio (TX): Psychological Corporation, 1981.
Vargha-Khadem F, Isaacs EB, Watkins KE. Medial temporal lobe             Wechsler D. Wechsler Memory Scale-Revised. San Antonio (TX):
versus diencephalic amnesia in childhood. J Clin Exp Neuropsychol        Psychological Corporation, 1987.
1992; 14: 371–2.
                                                                         Wiederholt JL, Bryant BR. Gray Oral Reading Tests-Revised. Austin
Vargha-Khadem F, Isaccs E, Mishkin M. Agnosia, alexia and a              (TX): Pro-Ed, 1986.
remarkable form of amnesia in an adolescent boy. Brain 1994; 117:
                                                                         Wilson B, Cockburn J, Baddeley A. The Rivermead Behavioural
683–703.
                                                                         Memory Test. Titchfield (England): Thames Valley Test Company,
Victor M, Agamanolis D. Amnesia due to lesions confined to the            1985.
hippocampus: a clinical-pathologic study. J Cogn Neurosci 1990;
                                                                         Wood FB, Brown IS, Felton RH. Long-term follow-up of a childhood
2: 246–57.
                                                                         amnesic syndrome. Brain Cogn 1989; 10: 76–86.
Wagner RK, Torgesen, JK. The nature of phonological processing           Zola-Morgan S, Squire LR, Amaral DG. Human amnesia and the
and its causal role in the acquisition of reading skills. Psychol Bull   medial temporal region: enduring memory impairment following a
1987; 101: 192–212.                                                      bilateral lesion limited to field CA1 of the hippocampus. J Neurosci
Warrington E. Recognition memory test. Windsor (Berkshire):              1986; 6: 2950–67.
NFER-Nelson, 1984.
Wechsler D. A standardized memory scale for clinical use. J Psychol      Received June 19, 1996. Revised October 10, 1996.
1945; 19: 87–95.                                                         Accepted November 5, 1996

								
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