Amnesia in Medical Practice

465 Conferences and Reviews Amnesia in Medical Practice Discussant JAMES A. TULSKY, MD This discussion was selectedfrom the weekly staffconferences in the Department ofMedicine, University ofCalifornia, San Francisco. Takenfrom a transcription, it has been edited by Nathan M. Bass, MD, PhD, Associate Professor of Medicine, under the direction ofLloyd H. Smith Jr, MD, Professor ofMedicine and Associate Dean in the School of Medicine. (Tulsky JA: Amnesia in medical practice. West J Med 1993;1 59:465-473) HOMER A. BOUSHEY, MD*: The topic chosenfor discus- peared preoccupied. His nurse feared he was having a sion in this conference involves the impairment ofmem- stroke and called an internist who worked in a nearby of- ory, a common problem among the elderly. The disorder fice. He did not examine the patient but reassured the that James A. Tulsky, MD, will discuss differsfrom most nurse that everything was probably OK and asked that she fonns ofmemory loss in the abruptness ofits occurrence call him back if this behavior continued. and its reversibility. At the end of the day the patient left his office and went to retrieve his car at the parking garage. One of the JAMES A. TULSKY, MDt: To introduce a discussion of am- attendants found him wandering aimlessly, for he could nesic syndromes, I present an illustrative case: not recollect where he had parked. His wife drove down- Case Presentation town, helped him find his car, and took him home. By this time, he was acting normally. His personal physician ex- The patient, a 71-year-old male physician without any amined him two days later and found no abnormalities. serious medical problems, awoke one morning to a world Two years later a similar episode occurred. This time that seemed "unreal." Despite this feeling of detachment, the physician was giving a lecture to a group of internal he went to the hospital, entered the operating room, and medicine residents. He last remembers walking into the performed a scheduled vaginal hysterectomy. He com- conference room and seeing someone "with a beard." Al- pleted the procedure in 45 minutes and without complica- though he does not recall giving the talk, he did receive a tions. He dictated his operative report and then looked in complimentary thank you note a week later. When he ar- on several patients. Although no mishaps occurred, to this rived at the office his nurse recognized his behavior from day he has no recollection of performing the operation. two years earlier. She called his son, a medical student in The obstetrics-gynecology resident who scrubbed on psychiatry rotation at a nearby hospital, and asked him to the case noticed that something was wrong, as the sur- come to the office. "Your father's having one of his geon repeatedly announced each step of the operation. 'spells' again," she said. When the son arrived, the patient For example, he said, "Now I am taking the cardinal liga- was perplexed and asked, "What are you doing here?" ment," over and over again while doing that procedure. "I came down because your nurse called and said you This behavior was unusual, even for this man who was weren't feeling well," replied the son. well known to teach during surgery. "I feel fine," responded the patient emphatically. His office nurse also began to suspect that something Then, with an expression on his face ofjust noticing his was wrong. Every hour that morning he called her up and son, he asked, "What are you doing here?" asked when his first patient was scheduled. She patiently After this sequence was repeated several times, the told him that his first appointment was a new patient patient changed topics and asked, "Where's Mother?" scheduled at noon. Because his office hours always "She's in Israel; she'll be coming back tomorrow," started at noon, these calls seemed unnecessary and answered the son. bizarre. At 1 PM he strolled into his office an hour late, un- With an expression of shock, the physician replied, aware that anything was wrong. His nurse noticed that he "Israel? How long has she been there?" looked "detached." He saw all the patients on his roster The son informed him, "She left three weeks ago." that afternoon, but spent little time with them and ap- Exasperated, the patient declared, "Israel. She's been *Professor and Vice Chair, Department of Medicine, University of California, gone three weeks? Oh, my, something is very wrong." San Francisco (UCSF), School of Medicine. tRobert Wood Johnson Chief Medical Resident, Department of Medicine, Then, after a slight pause and again with a fresh expres- UCSF School of Medicine. sion, he asked, "Where's Mother?" Reprint requests to James A. Tulsky, MD, Health Services Research Division, VA Medical Center, Duke University Medical Center, 501 Fulton St, Durham, NC 27705. 466 AMNESIA IN MEDICAL PRACTICE oped the ventricular localization theory that identified ABBREVIATIONS USED IN TEXT memory as a specific function of the brain located in the CT = computed tomography fourth ventricle. This theory was illustrated in a famous MRI = magnetic resonance imaging woodcut that appeared in his encyclopedia of the sci- NMDA = N-methyl-D-aspartate ences, the Marginata Philosophica (Figure 1). Rene Descartes (1596-1650), following up on this work, placed This last exchange was repeated at least ten times. As memory in the pineal gland. In 1664 Thomas Willis hard as he tried, the son could not break the cycle. Over (1621-1675) published the Cerebri Anatome, the most the next hour and a half, however, the patient's mentation complete and accurate description of the nervous system began to clear, and he was able to remember what was to that date. In addition to describing the cranial arteries told to him. He recognized that his memory was not nor- and nerves and coining the word "neurology," he recog- mal and repeated again and again, "God, I can't believe nized that the cerebrum was the organ of thought and that what happened." memory was located in the cortical gyri. Like most scientists of the time, Willis depended more on imagination Discussion This patient suffered from an episode of transient global amnesia. As would be expected from this bizarre, poorly understood, and benign disease, the patient is doing extremely well eight years later, having never experi- enced another episode. I have chosen to discuss transient global amnesia and the related disorders for three reasons. First, this is a surprisingly common problem that often presents to primary care physicians and yet about which little is known. Second, study of the amnesic syndromes has helped unlock the door to understanding the anatomy and pathophysiology of memory, a subject of enormous interest. And, finally, this patient was my father. Transient global amnesia is one of a group of amnesic syndromes that includes posttraumatic amnesia, drug-in- duced amnesia, Korsakoff's syndrome, and others. Al- though clinically separate and distinguishable, these vari- ous disorders share similar structural pathways. Our understanding of these diseases is a result of work in three fields: neuroanatomy, neuropsychology, and neurophysi- ology. After providing a background of the work in each of these fields, I shall discuss the individual clinical syndromes. Neuroanatomy of Memory Two thousand years of history passed before scientists learned that memory is formed and stored in the brain. The exploration of memory is rarely mentioned in classi- cal studies of medical history, and until this century, it Figure 1.-This woodcut by Gregor Reisch illustrates the ventric- was the purview of only a handful of neuroanatomists. ular localization theory of psychological functions. Messages from Hippocrates (circa 460-377 BC), the first great physi- the organs of hearing, sight, taste, and smell were thought to cian, never explicitly discussed memory. He did, how- unite in the sensus communis in the forepart of the front ventricle and to produce fantasy and imagination. Thought and judgment ever, understand that epilepsy was a function of the brain resided in the middle ventricle. Memory is located in the poste- and that damage to one side of that organ produced paral- rior fourth ventricle (Memoritiva). ysis and convulsions on the other side of the body. Plato (427-347 BC) mentioned memory and thought it was lo- than empiricism. Nevertheless, many of his descriptions cated in the mind. Aristotle (384-322 BC) placed it in the were surprisingly accurate. heart. Galen (131-201 AD), the accepted medical author- The power of modern neuroanatomic investigation of ity for centuries, never mentioned amnesia. Given that he memory has been the ability to correlate functional attended to injured gladiators and must have been witness deficits with anatomic lesions. Two famous cases pro- to episodes of posttraumatic amnesia, this oversight is pe- vided the basis for most of the knowledge until the intro- culiar.' duction of modern x-ray imaging techniques. The first of After a long period during which few important dis- these was "HM," a 27-year-old man who in 1953 un- coveries were made, Gregor Reisch (1467-1525) devel- derwent bilateral resection of the medial temporal lobe THE WESTERN JOURNAL OF MEDICINE * OCTOBER 1993 159 * 4 467 developed and confrm the earlier findings. A study of patients with permanent amnesia found substantial hip- pocampal abnormalities. A second study found patients with Korsakoff's disease to have damaged mamillary bodies and normal temporal lobes whereas patients with the characteristics of bitemporal amnesia had the opposite findings.34 Studies of monkeys have also helped to uncover the functional anatomy of the memory system.5 By using MRI imaging and stereotactic neurosurgery, monkey preparations have been created to evaluate the loss of each component of the medial temporal lobe memory system.

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