CASE 1
Report of Case
The patient, a retired professor of mathematics and languages, was first
examined at the Massachusetts General Hospital, Boston, when he was 84 years
old. Because he could give no medical history, it was provided by his devoted
wife of 38 years who was intelligent and objective. The patient had had a
distinguished career in academia. Earlier he had served on wartime duty as
an army officer. He had earned a degree in engineering. He taught and translated
French, German, and Spanish.
Four years before, at the age of 80 years, while traveling by train
to Cleveland, Ohio, with his wife to attend a wedding, he suddenly announced
that the conductor did not know where he was going and he wanted to get off
the train. He sought out the conductor who brought the patient back to his
train car where he did not recognize his wife. In the next several minutes
she became aware that her husband had lost his memory of his family, longtime
friends, his whereabouts, and his entire career. At the wedding he recognized
no one. There had been no injury, headache, weakness, slurred speech, change
in color, dizziness, imbalance, impaired alertness, jerking, incontinence,
facial asymmetry, or visual complaint. His health had been good. The amnesia
proved to be permanent.
In the following days the patient talked about his boyhood days on the
family farm in Minnesota and his love of horses. Rarely did he mention his
college days. He never spoke of his wartime service or his years as a teacher
and political activist. He did not recognize his home where he had lived for
38 years. Occasionally he might recognize his wife as a familiar figure and
ask her where his wife was. Almost from the time of onset, he began to say,
"I think we'd better go home"; this became the most prominent of several stereotyped
utterances ever since. In a few seconds, 60 years of his life were eliminated
from his memory.
Prior to the episode he had been remarkably well. Friends were amazed
at his physical stamina and mental keenness. He read widely and was interested
in everything. He could briskly ascend 5 flights of stairs. He did not smoke,
drank very occasionally, and took no medication.
After the onset of the amnesia he was able to carry on a rambling, superficially
plausible conversation. He could go out to dinner and go visiting without
attracting attention. He had not changed a great deal in the 4 years since
the initial episode. His wife thought that if she took him to a wedding at
that point, he would not act much differently than he had 4 years ago. At
first he continued to tend to his flowers but gave that up after 2 years as
he no longer could plan the planting or arrange the rows. Regarding the change
in speech that was to develop later, his wife did not notice any word-finding
difficulty at the time of the attack or since.
The patient seemed not to understand what his wife said to him, at least
he paid no attention except for simple commands. When asked to go to another
room to see what time it was, he forgot after 10 steps. If he repeated the
act several times, he might finally remember the time long enough to tell
his wife. He could tell time. He would eat breakfast and 2 minutes later ask
where it was. He might drink coffee and forget it immediately. He swept the
front sidewalk several times a day unaware that he had done it before. He
had to be reminded to bathe. When he went outside, if he crossed the street,
he was irretrievably lost. He remained an active walker and could walk for
hours. Once, when lost, he was found more than 20 miles away from home. He
might get up at night and insist on getting dressed and going for a walk.
In dressing he might put his clothes on over his pajamas. He sometimes put
on 3 pairs of socks. He was usually clean and never soiled himself.
He was mild mannered but, when crossed, he imperiously would say "Now
don't touch me and if you do, I have someone who will deal with you," or "I'll
have the police look after you." These were stereotyped remarks. According
to his wife, reasoning with him was of no avail.
He was able to express the names of simple things such as foods or clothing
but never made a complicated remark or used any novel word. He could write
his name. He was a "reading machine" and, in past years when he was well,
had liked to read aloud to his wife, who thought that "he had a basic love
to hear himself talk." (He was a lecturer.) Since the amnesic attack, he would
sit at home reading aloud for hours without understanding what he read. His
wife would walk away while the reading aloud continued. He never read silently.
On physical examination he was a healthy-looking elderly man. He was
right-handed, was 162.5 cm tall, and weighed 58.5 kg. He lay in bed seemingly
talking to someone and refused every request to carry out a neurological test.
He appeared somewhat hostile and rambled on using well-formed words that may
have made some sense, usually referring to caring for a third person. There
were frequently interspersed episodes when he told the examiner that he (the
patient) had had enough: "Now, will you get out or I'll have the authorities
see that you do."
His responses to the examiner's requests indicated some comprehension.
He closed his eyes on command. After 15 gentle requests that he put out his
tongue, he did not comply. Several minutes later after a few further requests,
he did so. When asked, "Are you Irish?" he responded, "No, I am not; I'm German,
altogether German!" When asked, "Where were you born?" he responded "Ohio."
He gave his age variously as 64, 35, 65, 14, 2 + 2 = 4, 12 x 12 = 144,
and 13 x 13 = 196 years. Often he failed to comprehend, perhaps most
often. At no time would he cooperate in naming objects. Yet, he picked up
a banana and named it correctly. When 1846 was suggested as his birthday,
he agreed. He read aloud fluently. After a tirade of abuse directed at the
examiner, the patient sometimes winked and chuckled.
He walked around his hospital room with good coordination. He looked
for his clothes in a pantry. He put on both slippers. He made fine coordinated
movements of the fingers. Vision seemed very good. He rambled on with simple
comments such as, "I'll put this over here and then this will perhaps fit
in here." When he tried to construct a simple sentence, speech deteriorated
into syllables, single words, or jargon. He packed toilet tissue in a box
with cookies and properly closed the box that was coming apart at the ends.
The results of a neurological examination apart from cognition were
essentially normal. The pupils were equal and reacted to light. The eye movements
were full. The face was symmetrical. There was no trace of dysarthria. The
arms and legs were used normally. Pinprick was felt everywhere. The tendon
reflexes were 2/4 in the arms and absent in the legs. The plantar responses
were flexor.
At the request of his wife, he slowly wrote his name with 2 spelling
errors, his street address and city with 1 error, and his wife's name and
address with 1 error. He wrote a jargon word for his sister-in-law's name.
The script was nonfluent.
He read aloud from books in English, French, German, and Spanish. He
appeared to understand nothing of what he read. According to his wife, for
the first year after the initial attack, he could translate a foreign tongue
into English, but not thereafter. According to his family he knew German and
French well at an early age, his father being German and his mother French.
While being observed over his shoulder, the patient read 2 pages from
a book in English with virtually no errors and with proper inflection for
questions and proper expression when he read the sentence "He became gloomier
at every step." When a German-language book was placed before him, he pronounced
many words correctly but made gross errors on many others. He pronounced the
German word war as "was." On repeated urging, he
gave the correct English translation of the German word erzähle as "tells." When a French-language book was placed before
him he read with good pronunciation (in French) and gave the English translation
of several words (for example, assez rapidement as
"sufficiently rapidly"). When a book in any of the 4 languages was placed
before him, he began at once to read it aloud "at a relentless pace." When
his reading was interrupted by questions or comments from the examiner, he
continued to read, occasionally making incoherent, irrelevant replies, that
is, the reading tendency dominated. If he lost his place in reading, he could
not find it. He did not carry out any written commands. One observer reported
that when the patient was still drowsy while recovering from thiopental sodium
(Pentothal) anesthesia, he spoke "normally." This interesting phenomenon was
noted again at the second admission to the hospital.
Results of laboratory studies showed no abnormalities. A left-sided
internal carotid artery angiogram was normal. An electrocardiogram was within
normal limits.
The patient was readmitted 5 months after being discharged from the
hospital. His wife reported little or no change in his behavior. He was usually
amenable to her guidance and became obstreperous only when his wishes were
overridden. He still managed his own toilet care. He balked at eating lunch
and supper. He watched television. He prayed in Spanish, French, German, or
English.
In the hospital he was agitated, belligerent, and uncontrollable. He
fought wildly when tended to and required the constant administration of tranquilizers
and sedatives. When quieted by medication, he was asked, "How are you?" to
which he replied, "I'm feeling alright." On another occasion when awakened
from a sedative-induced sleep, he spoke intelligibly in French mentioning
"the big lane to the house" and some other matters. He did not follow commands
given in French, Spanish, or English. He read the label on his coat correctly.
After 6 tumultuous days, he was transferred to a state institution for the
care of long-term psychiatric cases.
Soon after admission there, he became inactive, spoke very little, no
longer read, and was incontinent of bladder and bowel. He became bedridden
and died with a high fever 11 months later, 6 years from the onset of the
illness.
Autopsy showed that bronchopneumonia was the cause of death. General
postmortem examination showed no significant disease elsewhere. The heart
weighed 310 g. Neuropathologic examination of the brain revealed diffuse convolutional
atrophy with a clear impression of more marked involvement of both temporal
lobes. The hippocampal gyri were especially small. The brain weighed 1540
g. In the left inferior temporal gyrus there was an old, small cortical scar
1 cm in diameter and 1 to 2 mm deep, possibly vascular, possibly due to trauma.
This was the only focal lesion.
Microscopic examination of frozen sections of the left hippocampus stained
using the Bielschowsky silver technique showed widespread neurofibrillar changes
and abundant senile plaques indicative of AD. There was no selective loss
of neurons in the Sommer sector. Microscopic examination of sections of embedded
blocks of tissue stained with the Bodian silver method also showed widespread
changes of AD. The substantia nigra was well preserved. Purkinje cells were
normal.
Comment
The main feature of this patient's illness was the unexplained sudden
amnesia of a most severe degree involving a retrograde amnesia for some 60
years and a virtually total anterograde amnesia. In view of the later neuropathologic
finding of AD, it can be speculated that the unusual dysphasic manifestations
that were present 4 years after the onset reflected that process producing
a combination of amnesia and aphasia. The picture may have been colored by
the patient's unusual native talents.
The diagnosis of symptomatic AD is definite. No abnormalities were disclosed
that might account for the sudden, permanent amnesia. There was no evidence
of ischemic thalamic damage or healed encephalitis. The gross and microscopic
neuropathologic examinations were extensive. However, the state of the entire
hippocampus and fornix on each side may not have been fully scrutinized. A
brain weight of 1540 g in an 86-year-old man with AD is remarkable.
No medical or psychological assessment of the patient's cognitive function
was made in the 4 years after the onset of the illness. There is no reason
to doubt the wife's account of the acute amnesia. Whether AD was present and
progressing during the initial years is an important question. According to
the medical history he could translate a foreign tongue into English in the
first year but not thereafter. If this is true, it can be assumed that deterioration
occurred. Also his wife did not notice word-finding difficulty early on. There
is the history that the patient discontinued tending his garden after 2 years.
In the final year of the illness, the course was rapidly progressive. It is
possible or even likely that the patient's wife did not recognize a slow,
gradual, incremental decline in a mental state already complex and devastating.
In the absence of such an explanation, it would be necessary to explore a
possible direct relationship between loss of memory and the aphasic disturbance.
In an elderly person could an extremely severe amnesia give rise to elements
of an unusual dysphasia? There is no report of such in the literature. For
now the aphasic element must be attributed to AD. The acute amnesia is then
assigned to another mechanism, one of unknown nature.
CASE 2
Report of Case
A bank president, aged 70 years, came down to breakfast on the morning
of November 24, saying that he felt dizzy. His wife suggested that he drink
a little brandy and the patient opened a bottle. Twenty minutes later he asked
who opened the bottle and denied doing it himself. He was unable to find his
keys and stamps. It was evident to his family that his memory was severely
impaired. He did not recall visiting his daughter the day before. Prior to
the episode he had been extremely active and effective. There was no headache
at the time or in the past. He had not fallen. He was taking no medication.
He had received an influenza vaccination 10 days before.
When examined 10 days later, the family reported that there had been
no change in the interim. His day-to-day memory remained absent. Results of
a detailed neurological examination were normal except for memory. He was
affable, animated, and cooperative. There was no abulic delay in his responses.
He did not recall the national holiday of September 5th or the presidential
election day of November 2nd. He did not recall the last bank meeting 6 weeks
before. He knew that he had had a heart attack but did not realize it was
18 years ago. His memory for events of the past 20 years was impaired. Recall
of his high school and college years appeared to be adequate. There was no
aphasia. Reading and writing were performed normally. Proverbs were correctly
interpreted. There was no confabulation. Serial subtraction of 7 from 100
was done rapidly with 1 error (55). Given the sentence "Tom and Bill went
fishing, they caught 3 striped bass," he repeated it accurately after 12 minutes.
After 27 minutes, he recalled none of it even with prompting and when the
sentence was repeated, he disclaimed having heard it before.
The following laboratory tests and procedures were normal: skull x-ray
film, computed tomographic scan, electroencephalogram (awake and asleep),
bilateral carotid and left vertebral angiograms, cerebrospinal fluid examination,
and 20 blood chemistry studies (thyroxine level, 5.3 µg/dL [68 nmol/L]).
An electrocardiogram showed no conduction abnormality. A pneumoencephalogram
showed enlargement of the left temporal horn.
During the hospital stay of 12 days, memory function did not change.
An explanatory diagnosis was not achieved. A temporary cardiac arrest during
sleep was considered but against that interpretation is the fact that cerebral
low blood flow states do not cause ischemia of the hippocampi but rather of
the cerebral border-zones. The acute onset of the deficit and the finding
of normal spinal fluid exclude acute encephalitis.
The patient was examined each year thereafter. Ten years later his memory
loss was essentially unchanged. He could remember nothing from hour to hour.
He spent his time walking, reading, and playing solitaire. He kept a daily
diary. He did family chores under his wife's direction. His general health
was excellent. There had been no seizures or cardiac symptoms. Findings from
neurological examination were unremarkable. On the memory question, "Tom and
Bill went fishing, they caught 3 striped fish," after 5 minutes he did not
recall having been given a test. The sentence was given again and he repeated
it twice. After another 4 minutes, he recalled being given a test but could
not say what it was. His memories of high school and college were still preserved.
His memory for events of the previous 10 years was entirely missing and for
the 20 years before that, it was impaired as it had been on the original examination
10 years before. The family said that while he was normally volatile, he was
now docile.
At this time magnetic resonance imaging showed hyperintensity of the
hippocampus and hippocampal gyri bilaterally on T2 sequences (Figure 1).
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Axial magnetic resonance image showing increased T2 signal of medial
temporal lobes with some loss of tissue.
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He died suddenly of acute myocardial infarction at the age of 85 years.
According to his physician and the family, his amnesia and behavior did not
change during the entire 15 years.
Comment
A severe impairment of memory developed overnight in a 70-year-old,
healthy man. The deficit remained about the same for the next 10 years at
which point magnetic resonance imaging showed extensive, bilateral medial
temporal lobe abnormalities, resembling the picture reported in transient
global amnesia on diffusion-weighted imaging in the 2 to 28 hours after onset,
and clearing in the follow-up period.1 No report
of a similar case was found in the literature. As a possible mechanism one
could consider the process that underlies transient global amnesia in which
the insult was not transient but permanent. No such event has been reported.
CONCLUSIONS
