Tuesday, June 11, 2024

Searching Hard for Evidence of Strokes Causing Loss of Episodic or Conceptual Memories, They Come Up Short

The word "amnesia" is what you can call a "loaded" word. When a person thinks of amnesia he may think of some movie or TV show in which a person asks "who am I" and seems not to be able to remember who he is. But the term "amnesia" is defined as "a total or partial loss of memory."  Total memory loss is virtually never reported in the literature.  Almost always when people use the word "amnesia" they are talking about some memory difficulty that is much smaller than total memory loss.  

One of the most common forms of amnesia is what is called transient global amnesia. During an episode of such amnesia, a person may not recognize how he got to his current location. The person may repeatedly ask the same question, as if his ability to learn is temporarily blocked. Symptoms typically last  less than 24 hours, with complete recovery. It is interesting that transient global amnesia is not usually associated with any kind of brain injury. The cause of transient global amnesia is unknown. 

The medical literature reports two more long-lasting types of amnesia: retrograde amnesia (involving a problem in accessing already-formed memories) and anterograde amnesia (involving a problem in forming new memories or learning or memorizing).  Although many people define "retrograde amnesia" as an inability to access old memories, all or almost all case reports of such a thing are something much less than a complete inability to access old memories. In fact, the term "retrograde amnesia" is loosely used to describe all kinds of cases in which someone is slow or imperfect in accessing old memories or previously acquired knowledge.  So when you hear a claim of "retrograde amnesia," it is typically something much, much less severe than the way such a term is commonly defined.  Similarly, the term "anterograde amnesia" is loosely or carelessly used for a wide variety of learning or memorization shortfalls. So typically when such a term is used, someone is talking about a problem much less severe than a complete inability to form new memories. 

A group of scientists tried hard to get evidence that strokes can cause amnesia or memory loss. We read about the technique they used:

"The Medline database was searched through 2017 by combining the search terms 'stroke,' or 'cerebrovascular,' or 'ischemia,' or 'hemorrhage,' with the terms 'amnesia,' or 'memory'. The criteria not 'subarachnoid,' not 'dementia,' not 'cardiac arrest,' not 'transient global amnesia' were also added and search returns were limited to human studies. This search returned 4855 possible matches. These returns were limited to English language articles, and the titles of 1000 papers most related to the search criteria were reviewed, identifying the most relevant 500 papers. These abstracts were reviewed, identifying the most relevant English language papers. Abstract review looked for articles on human studies, primarily about a patient with memory loss, memory loss acquired by a lesion, and the etiology was not transient global amnesia, not Alzheimer’s disease-related, and not a brain tumor or other non-acquired lesions. From this set, we reviewed 250 full-text articles and included reports that fit the following criteria: (1) Case report format or individual case description; (2) Adult population; (3) Clinically relevant episodic memory deficits by bedside or neuropsychological tests attributed by the authors to an acute brain lesion; (4) Availability of a CT or MRI image depicting the lesion location(s) of sufficient quality that the lesion could be transcribed onto a standard brain template (Supplementary Fig. 1). Fifty-three cases of amnesia were found with identifiable causative brain lesions (mean age 57.5 ± 13 years, range 27–72, 66% male). '

To get a list of the 53 papers, you must consult Table 1 of the Supplemental Information part of the paper, which can be read here.  At the end of the table listing the papers, we read this:

"References for the 53 case studies meeting inclusion criteria for our analysis, taken from 50 unique journal articles. All 53 lesion cases were classified as “severe” amnesia (the memory deficit was clinically apparent even without formal neuropsychological testing), involved anterograde memory loss, and included documented impairment in verbal memory. 30/53 cases reported a formal measure of amnesia severity, but the metrics varied. The most common metric was the Weschler Memory Scale general score (13 cases) followed by Cambridge Cognitive Examination memory score (five cases). Only nine cases provided both a Wechsler Memory Scale  general score and IQ score to allow for the calculation of a WMS discrepancy score. 19/53 cases reported whether there was some element of retrograde amnesia: 18/53 reported impairment while one reported that retrograde memory was intact. Only one case reported a score for retrograde amnesia via neuropsychological testing. 20/53 cases reported whether visual memory was impaired, all 20 of which reported impairment. Seven cases reported formal scores for visual memory impairment using the Benton Visual Memory Task. Finally, other characteristics of amnesia were rarely reported such as impairment in semantic memory (four cases), autobiographical memory (two cases), or temporal order memory (one case)."

The confession at the end is interesting. The authors confess that they found almost no evidence of semantic memory being disturbed by strokes, and almost no evidence of autobiographical memory being disturbed by strokes. That is not something we would expect under the hypothesis that memories are stored in brains. Under such a hypothesis you might expect to very often hear of someone whose autobiographical memories were damaged after he had a stroke. 

Below is a table I made discussing some of the cases listed in Table 1 of the paper, as many as I can find.  I may note that many of the titles and quotes use inappropriate adjectives and nouns.  A neuroscientist wishing to maximize his chance of getting a paper published may tend to use the word "amnesia" for something that is a mere performance shortcoming, and may also use the word "severe" to describe something that is not very severe at all.  The more dramatic the report sounds, the higher the chance will be that the paper will be published, to the benefit of such a neuroscientist.  We must remember that scientists live in a "publish or perish" culture in which it is as if the key goal of their lives is to get as many papers published, with as many citations as possible.  In such a culture exaggeration is to be expected. In fact, in today's world of neuroscience it is massively common for papers to have titles that do not accurately describe the research findings made, and it is also massively common for papers to have claims in their abstracts that are not justified by any findings reported. 

In quite a few of the cases I will discuss below,  amnesia or "amnesic syndrome" is claimed, but inadequate evidence is given for such a claim. You can only reliably verify a claim of long-lasting amnesia by careful tests done on multiple days. There are any number of short-term reasons why a person might perform poorly on some quick memory test on a particular day. The person might be distracted or indifferent or in pain or not paying attention or in a foggy state of mind.  So, for example, the fact that a patient is asked to repeat words he was told to remember (after a gap of five minutes) is no strong evidence of "anterograde amnesia."  There are any number of reasons why someone might say "I don't remember" when asked to remember something like words he was told to remember five minutes ago, or asked for the names of the presidents before the current president. Explanations such as lack of effort or indifference or distraction (extremely common effects) are the most plausible explanation for such failures rather than the exotic explanation of stroke-produced amnesia. The visual below illustrates the point:

amnesia

Here is the table showing the papers from Table 1 of the paper mentioned above. I omit almost all papers that were behind paywalls, making it too difficult to find the relevant details. 


Paper

Description

Comment

Amnesia after a discrete basal forebrain lesion

A man had surgery for a 5 mm. aneurysm in his brain. "Immediately after the surgery, he developed disorientation and agitation." 

Although the man's state is  described in the paper as amnesia, nothing very serious-seeming is described.  We hear vague mentions of "difficulties" without much in the way of specifics. 

Teaching NeuroImages: amnesia due to fornix infarction

We hear vaguely of "acute confusion and short-term memory difficulties, including significant retrograde and anterograde amnesia," but get no specifics. 

The abstract fails to convincingly link this case to any brain problem. We hear a claim that "small vessel disease" was "the most likely cause," but no evidence to support that claim. 

Clinical Reasoning: A puzzling case of amnesia

A woman "could not recall events that occurred in a 2-week period surrounding neurosurgery."  Since that sentence does not use "any events," we do not know how serious a memory difficulty was involved. 

We get no specifics documenting that any real amnesia occurred.   The report is too vague to conclude that amnesia really occurred to any large degree. 

Fractionation of memory in medial temporal lobe amnesia

We hear of a patient RH with mild memory difficulties and a patient JC with poor visual and verbal recall,  Regarding Patient RH, we read, "the volume of her right hippocampus was 58.6% smaller than her left hippocampus." Patient RH "with selective right hippocampal damage, performed well on several verbal memory tests and her estimates of recollection and familiarity for words were normal." But "RH’s performance on standard tests of prose recall and a test of delayed recall for names was poor."  We read, "RH performed normally on tests employing human faces."  But "the bilateral hippocampal amnesic, JC, showed a profound verbal memory impairment."

Neither of the cases is  amnesia according to common understanding of the word.  We seem to have learning difficulties related to speech, visual perception or language processing.  Although we are given evidence Patient RH had brain damage, we are given no convincing evidence that Patient JC had any brain damage.  The paper claims that JC had "bilateral hippocampal damage" but provides no compelling evidence to back up such a claim, and we are told his  "neurological examination was unremarkable," contradicting such a claim.. 

Pure amnesia after unilateral left polar thalamic infarct: topographic and sequential neuropsychological and metabolic (PET) correlations

 15 days after experiencing severe turbulence on a flight, a woman admitted to a hospital was "unable to recall her profession." "During the first few days, she was slow, easily tired, and disoriented in time, but she always knew that she was in a hospital and found her way around easily. Her behaviour and contact with the examiners was always adequate. Spoken and written language, praxias, visuocognitive functions, and spatial orientation were largely preserved.... with the exception of difficulties in naming objects and people." "Memory testing ... revealed sparing of short term memory and preserved learning of new skills, but major deficits in episodic memory and in acquisition of new material. The latter deficit was always more severe for verbal than non-verbal material." "The patient read fluently and, 4 months after the onset of the illness, was able to recall a read story." 

Despite the "pure amnesia" in the title, the evidence prevented for memory dysfunction is spotty.  We read of a small one-centimeter lesion found in the patient's brain, but we don't knew whether this was the cause of her problem.  Some of the trouble might be related to psychological trauma from the flight turbulence. 

"Frontal Verbal Amnesia"

A man "noted the sudden onset of difficulty in speaking and weakness of the right side of his body."  "The patient performed normally on a wide range of language tasks and exhibited a normal verbal IQ. In spite of his at least relatively normal language skills, however, he has a marked verbal memory deficit with sparing of nonverbal memory."

It seems misleading for the authors to have called this case "amnesia." The dysfunction documented is very limited. 

"Cognitive disconnective syndrome by single strategic strokes in vascular dementia.


Six cases are described in too sketchy a manner for one to draw any conclusion about memory effects of a stroke. 

"Amnesia following thalamic hemorrhage. Another stroke syndrome"

"Results of standard psychometric tests indicated above-average intellectual ability. On the Weschler Adult Intel1igence Test his verbal IQ was 111, performance IQ 108, and full-scale IQ 110. No obvious verbal performance discrepancy was present, but administration of the Weschler Memory Scale yielded a memory quotient below normal and impaired ability for new verbal learning." The patient soon died. 

Another case of the inappropriate use of the word "amnesia" for mere sub-normal test performance.  No evidence for amnesia is documented. 

"Memory loss from a subcortical white matter infarct."

"He was able to repeat four numbers forward, could not recall any of three objects after 3 minutes, but was able to remember recent presidents. Spontaneous speech was grammatically correct with mild hesitancy on initiation of sentences and a tendency towards echolalia. Repetition, naming, reading and writing were all preserved. Verbal comprehension was mildly impaired only when dependent upon understanding complex syntactic relationships. Finger naming, right/left orientation and calculations were normal. Visual-spatial testing of spontaneously drawn and copied figures was normal. ... Neuropsychological assessment included Form I of the Wechsler Memory Scale. Despite scoring nearly flawlessly on the personal information (6/6) and orientation (4/5) subtests, the patient only recalled 4/24 and 2/22 memories from the logical memory subtest (about 2 SD below that expected for his intelligence and age).... In contrast, nonverbal memory function was less affected, as shown by his visual reproduction subtest score (4/14), only 1 SD below mean."

Another misleading paper title. After an apparent stroke, the subject seemed to have only a minor performance defect in memory tests. 

"Bilateral hippocampal infarction and amnesia:A case report"

"The mild confusion was present in the form of constant repetition of the same questions as well as the temporal and spatial disorientation." But the patient scored 23 and three months later scored 25 on the MMSE test, the second score requiring fairly good memory (a score of 26 being normal). And the patient scored normally on a Digits Span Forward memory test and  Digit Span Backward memory test. 

The paper claims "Severe anterograde amnesic syndrome, related to the domain of episodic memory, dominated," and claims that "the patient was unable to recall any of the previously presented information."  The claims are not backed up by robust evidence, and are contradicted by the MMSE scores given and the Digit Span scores given. 

"Acute bilateral thalamic infarction as a cause of acute dementia and hypophonia after occlusion of the artery of Percheron."


No claim of amnesia is made, and no proof is given that the patient suffered from dementia. We merely read the hesitant claim that "after all these tests and the total clinical assessment of the patient, thalamic dementia was under a reasonable consideration." 

No evidence is given for amnesia, and the only evidence given for dementia is a single MMSE test with a score below 18. 

"Where am I?’ –An unusual stroke presentation"

We read of a man who had a stroke, and we hear the claim that he "he had no recollection of events of the past decade." Since this statement does not contain the word "any" we have no idea of how bad the memory problem was. 

The paper is a very short one, and we have no specifics of memory tests. So it is unclear how bad this person's memory problem was. It is also not clear that stroke caused any memory problem the man had. 

"Retrosplenial amnesia without topographicdisorientation caused by a lesion in the nondominanthemisphere"

An old man had "normal remote memory," and the claim is made he had trouble navigating in the hospital because of "amnesia."  We have the claim that "he could not learn the disease name, patient room number, and the primary physician's name, suggesting mainly anterograde amnesia." But no proof is provided for such a claim. 

There could be details supporting the claim of anterograde amnesia, but none are found outside of a paywall. We don't know whether other issues might have caused the patient to fail to learn the items mentioned. 

"The paramedian diencephalic syndrome: a dynamic phenomenon"

We read of an attorney who had a variety of problems after a heart operation. We hear of a downward gaze, lack of attention to doctors and confabulation. and we get a vague reference to "amnesic syndrome."  

We don't get specific details about memory loss. We read that the patient did well on "repetition" and "naming," and that on reading and writing his performance varied from normal to grossly deficient. 

"Migrainous stroke causing thalamic infarction and amnesia during treatment with propranolol"

We hear a claim that a patient  "had significant confusion and amnesia."  But we get no details backing up that claim, and no mention is made of a chronic memory problem.


"Amnesia due to fornix infarction"

We hear that a 71-year-old with brain lesions had " anterograde amnesia for verbal and visual information,"  although we don't hear of much to support that claim.  We read, "Her immediate memory for the Rey-Osterreith Complex Figure... was at the first percentile, and after a delay, it was nonexistent. Her performance was average on the Boston Naming Test and Wisconsin Card Sorting Test."  We read, "On the follow-up visit 1 month later, she showed significant improvement in her short-term memory. She was able to recall 3 objects after 5 minutes and displayed marked progress in her ability to register verbal and visual information. However, she had no recall of the events of her hospitalization." 

No evidence has been given here of serious amnesia, other than forgetting events of a hospitalization. 

"Amnestic Syndrome of the Subcallosal Artery: A Novel Infarct Syndrome"


The paper is half-way behind a paywall. The part we can read makes no mention of loss of episodic or conceptual memories, but merely claims "severely impaired recall of both verbal and visual information," and mentions an inability to recall three words after three minutes. 


Unilateral Amnesic Stroke

The paper confesses "reports of amnesic syndromes due to unilateral stroke have appeared infrequently and unsystematically." It presents six cases it claims are examples of "amnesic stroke." No evidence is presented of any serious long-lasting amnesia in any of the six patients.  We merely hear spotty reports of imperfect performance on some memory tests (such as remembering 3 words after 3 minutes, but not after 5 minutes), and a few anecdotal reports of scattered failures such as a failure to name past presidents. 

The authors are using the term "amnesic stroke" without adequate warrant.  The old people described have memory shortcomings common in old people. I may note that failing to name three words you were asked to remember after five minutes is never convincing evidence of memory impairment, unless verified in multiple tests on different days. There are any number of reasons (pain, distraction, indifference, etc.) why a person might not answer such a question at a particular time. 

"Bilateral posterior cerebral artery infarction"

Other than mention of confusion upon being admitted to the hospital, we hear mention only of a short-term memory problem, but no specifics. 

We have here an example of writers making unjustified use of the term "amnesic syndrome." We read: "There was evidence of a profound amnesic syndrome with impaired delayed recall (0/3 on Mini-Mental State Examination recall). He could not remember why he had been brought to the hospital." The MMSE mention is a mere mention of failing to recall three words you were asked to remember.  There are any number of reasons why a person might fail such a request other than amnesia (distraction, indifference, etc.).  Failing to remember why you were brought to hospital is no strong evidence of amnesia. 

Hippocampal Lesion Patterns in Acute Posterior Cerebral Artery Stroke

We have some memory tests on patients who had damage to the hippocampus because of a stroke infarct, who are referred to below as HI patients (hippocampal infarct patients).  We read, "In the MMSE, the patients reached a score of 24.30±3.91 (lying in the mildly impaired range), with no difference between groups, t(18)=1.33, P=0.202. In the Clock Drawing Test, the patients reached a score of 2.84±1.26 (at the border of the normal range), with no difference between groups, t(17)=0.51, P=0.618."  In regard to results of a RBMT test of long-term verbal memory, we read this: "Compared to normative samples, the scores of patients with left HI were within the mildly impaired range, whereas the scores of patients with right HI were only slightly below the mean of the normative sample." 

The results defy common claims that the hippocampus is crucial for memory. We have hippocampus- damaged patients who have performed fairly well on memory tests. 

"Diaschisis after thalamic stroke: a comparison of metabolic and structural changes in a patient with amnesic syndrome"


The paper wrongly claims it has a patient with "classic amnesic syndrome," but it provides no data backing up that claim. The patient's MMSE score (largely a memory test) was above-average for a patient of her age, and we merely read of a "mild semantic memory disorder." 


"Amnestic Syndrome and Vertical Gaze Palsy: Early Detection of Bilateral Thalamic Infarction by CT and NMR."


We read of a 27-year-old acting in a strange and sleepy manner. Her memory performance is spotty. "Long term memory was affected in an uneven fashion. Previous addresses, jobs, and acquaintances were recited accurately, but she was unable to give her phone number, and could not name present or past California governors or U.S. presidents. Digit span, however, was excellent — seven digits forward and five in reverse. Affect was characterized by indifference, facetiousness, and paucity of spontaneous speech."  We are told, "At three months she was felt by friends and family to have entirely recovered, and on neurologic exam was normal." 

The case was too short-lived and spotty to be called a serious case of amnesia. 

"A case of amnestic syndrome due to right thalamic infarction"

A 66-year-old is described with only minor mental symptoms, and she seems to have near-normal memory performance.  No justification is given for a claim of "amnesic syndrome." 


 "Preserved complex emotion-based learning in amnesia"

We have a report of an 85-year-old man with some bad memory performance, and we hear that he had a stroke. But there is no evidence given that his bad memory was a sudden result of his stroke. Strangely the same person performed above-average on some memory tasks. 

It is well-known that very many very old people have memory problems. The paper does not make clear whether this person's memory problems came on gradually, or resulted suddenly from a stroke. 

"Retrospinal amnesia"

We read of a 39-year-old man who was hospitalized with a severe headache. He apparently had some kind of stroke or infarction, and had a brain operation while hospitalized. We read, "All language and language-related functions were intact, as was performance on tasks associated with frontal-subcortical functions (i.e., Verbal Fluency (Benton, 1968; Lezak, 1976), Proverb Interpretations, Stroop, Visual-Verbal Test (Siegel, 1957))." We hear a claim that he had "profound amnesia," but that is followed by a claim that "His remote memory, however, appeared intact, as assessed by the Albert Remote Memory Battery (Albert el al., 1979)."  We hear of poor performance on verbal memory tests asking a subject to remember words and stories, but we are told "he performed much better on nonverbal recent memory tasks."  We are told, "T.R.'s memory deficit was to some extent material-specific. Verbal tasks showed a consistent deficit; while tests of nonverbal memory, except for the Rey-Osterreith Complex Figure Test, were performed normally."  We are told he "he had remarkably intact general intellectual functions.' 

The patient seems to have had some brain problem causing some kind of  deterioration in verbal processing.  No very strong evidence has been given of a loss of old  episodic or conceptual memories, other than some scattered anecdotes. 

"THE SEPTO-HIPPOCAMPAL PATHWAYS AND THEIR RELEVANCE TO HUMAN MEMORY: A CASE REPORT."


We hear of a young man who went to the hospital with a bad headache, and who then had a brain operation. We read, "Autobiographical memory revealed an almost complete loss of information from the two months prior surgery. Otherwise, major personal events were preserved, although some details, particularly events of the preceding year, were no longer available. His domain-specific (professional) knowledge was by and large spared."  We hear about a low performance in memory tests, but also are cautioned that the patient had low motivation, which might have produced scores lower than could have been produced if he were motivated. 


"Diencephalic amnesia and apraxia after left thalamic infarction"


We read of a 78-year-old woman speaking only Hungarian hospitalized in Australia because of strange behavior.  The evidence value of the report is limited by the lack of any test scores, and by the fact that the woman was questioned not directly by the doctor, but through an interpreter, because she spoke a language the doctor did not speak.  We have no idea of how accurate the translation was (presumably those who speak Hungarian are rare in Australia). We read this: " She acknowledged she was in a hospital, but maintained it was in Budapest and the year was 1947. Although her recollections regarding her early life and wartime Hungary seemed accurate, she confabulated when asked for details of recent events." But how long did this strange state last? We are not told. We are merely told that 3 months later the woman still had some kind of memory problem. 

The lack of a detailed follow-up report on this strange case is suspicious. We may reasonably suspect that the strange described condition was a short-term thing, and we may wonder whether some glitch in language translation was largely responsible for the strange report. We have no clear evidence of a stroke, but merely read of an fMRI showing something "consistent with a stroke."

"Acute Korsakoff Syndrome Following Mammillothalamic Tract Infarction"


We have this claim about a 56-year-old man: "In addition to anterograde amnesia, he also had retrograde amnesia and could not recall events of the previous 4 years."  The lack of the word "any" in such a sentence leaves it unclear how bad the man's recall of events of the past four years was. The only specifics we are given is the claim that the man did not believe that his father had died, which has occurred two years earlier.  We are told, "The level of general intelligence, previously learned skills, immediate recall, and ability to calculate in short formulae were retained."  We read a claim that the man's memory had not improved 4 weeks later and 8 weeks, although no evidence is given for such claims, except for the claim that the man still did not believe his father had died. 

We have no test scores and no specifics to back up the claim of either antegrade or retrograde amnesia, other than a vague statement that the patient "could not recall events of the previous 4 years" without making it clear whether the author meant "any events," and the claim that the patient did not acknowledge his father's death (which might have occurred for any number of reasons not related to memory).  The patient could have had amnesia, but the paper fails to document such a condition in any convincing way. 

I must reiterate some important points here:

  • Scientists and many doctors live in a "publish or perish" culture in which they are largely judged on the basis on how many scientific papers they have produced, and how many citations such papers have got. In such a situation we should expect for there often to occur exaggerated claims in scientific papers, and that does occur massively. So we should be suspicious of all uses of the word "amnesia" or claims of "severe amnesia" or "acute amnesia," and wonder whether such language has been chosen to maximize the chance of paper publication and paper citation. 
  • Extraordinary claims of amnesia require very strong evidence, which is typically lacking in the reports above. 
  • It is fallacious to cite a single case of low performance on a memory test as proof of amnesia, as there are any number of reasons other than amnesia why a person might perform poorly on a memory test (reasons such as distraction or indifference or failing to understand the speaker).  Patients often don't understand English well, and doctors often speak English in a thick accent, a factor that by itself can explain poor performance on a verbally-given memory test. 
  • You have given no clear evidence of amnesia by a claim such as "the patient could not remember events of the past year," because such a statement (lacking the word "any") leaves it unclear whether the patient could not remember any events or merely could not remember some events. 
  • It is usually impossible to tell when a stroke occurred and often impossible to tell if a stroke occurred, so claims of a stroke cause in the cases above are typically questionable, and often involve guesswork.  A paper claiming that brain scan results are "consistent" with a stroke has typically not shown that a stroke occurred, and has not shown that stroke caused the observed memory performance shortfall. 

The end result here is that none of these papers convincingly demonstrate a permanent loss of episodic memories or conceptual memories from a stroke event.  Overall, the results are consistent with the claim that memories are not stored in the human brain. 

No comments:

Post a Comment