Everything in Its Place

by Oliver Sacks

  It was not apparent that there was anything amiss until March of 2001, when he went to Paris on a business trip. There were hints of disorganization and excitement while he was preparing for the trip, and in Paris, these symptoms became full-blown: he forgot important appointments (which brought matters to his family’s attention), bought more than a hundred thousand dollars’ worth of art books, had altercations with the hotel staff, and assaulted a policeman at the Louvre.

  This precipitated his admission to a French psychiatric hospital, where he appeared “grandiose and disinhibited” and confessed that, unknown to anyone else, he had increased his prednisone dosage to five times his original prescription. He had been at this elevated dose for at least three months. Clearly this high dosage had produced what is known as a “steroid psychosis,” and Mr. K. was diagnosed as having “a manic episode with psychotic features.” He was put on tranquilizers for the mania, and his prednisone dose was reduced to the original ten milligrams twice a day. But this had little effect, and after some days in the French hospital, still noisy and disinhibited, he was returned to New York on April 30, 2001, in the company of a physician.

  Back in New York, Mr. K. was again admitted to a psychiatric ward; despite the drastic reduction in his steroids, he still seemed psychotic and markedly disorganized in his thinking. Neuropsychological tests showed a decline in his previously superior IQ, memory, language, and visuospatial functions.

  Since no evidence could be found for any infectious, inflammatory, or toxic-metabolic cause for Mr. K.’s persisting cognitive deficits, his physicians felt that there must be a rapidly progressing neurodegenerative disease—in addition to (and perhaps predisposing him to or unleashed by) the steroid psychosis. Alzheimer’s disease, Lewy body disease, and especially frontotemporal dementia were considered.

  MRI and PET scan imaging of Mr. K.’s brain revealed reduced metabolism bilaterally—an inconclusive finding, but one that, together with his neuropsychological tests, was compatible with early dementia.

  When Mr. K. was finally discharged home in early June, after six weeks in the hospital, he became more agitated and confused than ever, on one occasion attacking his wife. He now needed round-the-clock supervision, and he was admitted to a locked Alzheimer’s facility. Here things rapidly went from bad to worse. He started to hoard food, to steal belongings from other residents, to become dirty and dilapidated—a drastic change for this previously meticulous dresser.

  His wife, dismayed by the rapid disintegration of her husband, sought a new neurological opinion in mid-July. Mr. K.’s new doctor ordered more tests and began to taper Mr. K.’s dosage of prednisone further.

  By September of 2001, after a year of continuous administration, Mr. K.’s steroids were finally stopped completely. His confusion diminished almost immediately. This was strikingly clear at a family wedding in the middle of the month—Mr. K., restored to his former dapper appearance, recognized most of the guests, greeting and chatting with them in a way that would have been inconceivable a month before, when he had been so grossly demented.

  Mr. K. had already returned to his business, and neuropsychological tests a couple of weeks later showed great improvement in almost all of his cognitive functions, although there were still hints of impulsiveness, perseveration, and some intellectual deficits.

  All this was very reassuring, but perplexing, too, for diseases like Alzheimer’s and frontotemporal dementia are progressive—they do not go away virtually overnight. And yet here was Mr. K., at one point expected to spend the rest of his days in a locked Alzheimer’s facility, now restored to his family, his business, to life as usual—as if suddenly awakened from a hideous, months-long nightmare. (His wife, who wrote a narrative of her husband’s experiences, titled it “A Journey to Hell and Back.”)

  * * *

  —

  I FIRST MET Mr. K. about six months after this, in March 2002. He was a tall, amiable man, well dressed, affable, and voluble. He presented his story rationally and consecutively, but with numerous asides. (It was not clear how much he was recollecting his own experiences, and how much he had been told his story by others, and now had it well rehearsed and fluent.) He was persuasive and charming, and talked freely about other aspects of his life—his interest in art, his wish to write a book about more than a hundred little-known art museums in Europe and to make a virtual online museum of their treasures. He was exuberant, expansive and loquacious when he spoke of all this, and I wondered whether there was an impulsive, “frontal-lobe” flavor to his thinking, as might happen with an incipient frontotemporal dementia. And yet I could not be sure without knowing the patient for a longer time, in depth; perhaps, as his wife insisted, this high-energy ebullience was normal for him.

  Recent neurobehavioral testing had revealed that he still showed a tendency to perseveration, impulsivity, inattentiveness in scanning, and memory retrieval deficits—a pattern suggestive, though not diagnostic, of mild frontal lobe and hippocampal dysfunction.

  My neurological examination of Mr. K. was unremarkable, apart from a tremor of his left hand. He had now been off all drugs for several weeks, and his mild parkinsonism had almost entirely disappeared. It was evident, however, that he and his wife were haunted by the uncertainty his physicians had expressed, and which they themselves shared. “Hopefully a steroid psychosis is what it was,” Mr. K. said, “but there may have been other underlying causes. Maybe the beginnings of Alzheimer’s. What concerns me is that there was no definitive diagnosis. Was it just steroids, or something more serious coming around the bend?” If there was indeed a neurological disease, temporarily unmasked or unleashed by the steroids, was it not still hanging over him, waiting to cause a more irrevocable dementia? Both husband and wife used the term “lurking,” and wondered if there was anything more to be done to provide reassurance and a clearer diagnosis.

  I could not give the definitive answer they wanted—the whole business was a strange one. There was dispute in the neurological literature as to whether such an entity as “steroid-induced dementia” even existed, and, if so, what its prognosis might be—recovery had been reported in some cases, not in others.

  Unable to offer Mr. K. a conclusive diagnosis but reassured by his manifest improvement, I advised him to resume all of his normal activities, hoping that his work, which necessitated much traveling and making complex decisions and negotiations, would give him some reassurance, along with a renewed sense of identity and optimism. When I next saw him, six months later, he told me he had indeed been working very hard: “My illness cost my business dearly. I’m trying to put it back together again.”

  I followed up with Mr. K. at intervals, and in May 2006—five years after his strange attack of dementia—he scored at a very superior level on tests of mental function across the board. He had recently returned from Europe and Turkey, he told me, and planned to open a business in Dubai. He gave me a fascinating capsule history of the fur trade, and said he intended to move ahead with his online museum.

  “Absolutely no carryover from the past,” he said. “Almost as if it never happened.”

  * * *

  —

  DEMENTIA IS OFTEN SEEN as irreversible—and indeed, in the context of a neurodegenerative disease, it may be so. But there are also dementias so severe as to mimic advanced Alzheimer’s disease that may nonetheless be reversible. These are not uncommon in the aging, where inadequate diet and vitamin B12 deficiency can lead to neural decline. And to the many possible causes of such reversible dementias—metabolic and toxic disturbances, nutritional imbalances, even psychological stress—excessive use of steroids has to be added. The danger sign, perhaps, is the feeling of extreme well-being they may produce, the euphoria that Mr. K. was so quick to recognize, yet so powerless to resist.

  Tea and Toast

  Theresa was in her mid-nineties when admitted to Beth Abraham in 1968. She had slid into a gradually
advancing dementia since the age of ninety, though with help from a niece and a visiting nurse, she continued living alone and maintaining a semi-independent existence. But her diet was poor—she lived, her niece told me, on “tea and toast.” And now she was becoming confused and incontinent, and needed the care of a nursing home.

  She had not apparently had any strokes or seizures, and the default diagnosis was therefore one of “senility,” or “SDAT” (senile dementia of Alzheimer type, as we termed it then), a progressive and incurable condition. Outside this there were no abnormalities noted on her general or neurological examination, and routine blood tests showed levels within normal limits. But I was suspicious when I heard of her tea-and-toast diet, and ordered a test that was then somewhat unusual—an assessment of the vitamin B12 level in her serum. The normal range of B12 is between 250 and 1,000 units, but Theresa’s blood level, it turned out, was only 45.

  This condition, pernicious anemia, is sometimes due to an autoimmune disorder, but more commonly it results from a vegetarian diet. Injections of liver extract were once the standard treatment for such anemia, as it had been observed since the 1920s that eating animal foods, and especially liver, could prevent, halt, or reverse what had been seen as a deficiency disease—though the special factor that made meat, and especially liver, so efficacious was unknown. (George Bernard Shaw, a strict vegetarian, had liver extract injections monthly and, with their help, was able to live to ninety-four, active and creative to the last.)

  Repeated attempts to extract the anti-anemia principle in liver were finally successful in 1948—and that same year, when I was fifteen, we had a school visit to the very laboratory where it had been extracted and concentrated from liver (almost as radium had been extracted from pitchblende). We were told that this principle was vitamin B12, or cyanocobalamin, a complex organic compound with a cobalt atom at its center; it had the same beautiful rose-red color characteristic of simple inorganic cobalt salts. This discovery made it possible to test levels of B12 in a patient’s blood and to treat the patient, if necessary, with “the red vitamin.”*1

  Kinnier Wilson, a neurologist of encyclopedic knowledge, had observed early in the twentieth century that pernicious anemia might, in fact, cause only a dementia or a psychosis, without any accompanying anemia, or any neuropathy or spinal cord degeneration—and that such dementia or psychosis might be largely reversible by liver injections, in contrast to the irreversible structural changes that may occur in the spinal cord when the cause is an autoimmune disorder.*2

  Could this be the case with my old lady? Would her dementia prove reversible if we gave her vitamin B12? To our delight and amazement (for we had thought she might have Alzheimer’s disease in addition to B12 deficiency), she started to get better with weekly injections of B12. She regained her fluency and memory; she started to go to the hospital library daily, first to look at newspapers and magazines, then to take out books, novels and biographies, the first real reading she had done in nearly five years. She also started back on crossword puzzles, to which she had been addicted. After six months on vitamin B12 injections, she was fully restored and capable of taking charge of her own life and affairs. At this point, she wanted to discharge herself and go back to living at home.

  We agreed, though we cautioned her to maintain a full diet, have periodic monitoring of her B12 levels, and take injections as long as they might be needed.

  Two years after her discharge from Beth Abraham, Theresa, at ninety-seven, was doing well but still in need of B12 injections. This is the case with many elderly people, whatever their diets, for they often tend to have low gastric acid. (This can be made worse by the medications, such as the proton pump inhibitors, often given for acid reflux, for these can completely prevent the secretion of gastric acid.)

  While Theresa was the first, I have now seen similar confusions and dementias due to vitamin B12 deficiency in a number of old people, and it is not always reversible. But Theresa was lucky. “The red vitamin,” she said, “it saved my life.”

  *1 . It was only in the 1970s that it became possible, in a great feat of synthetic chemistry, to synthesize B12.

  *2 . Sándor Ferenczi, the great psychoanalyst, started developing some very unusual ideas in the early 1930s—that analysts, for example, should lie down on the analytic couch beside their patients. These ideas, albeit a little heretical, were at first seen as expressions of his remarkable originality of mind, but as they grew wilder it became evident that Ferenczi had an organic psychosis, which turned out to be associated with pernicious anemia.

  Telling

  Even before my own medical education, I learned an essential truth about doctoring from my parents, both physicians: that being a physician involves much more than handing out diagnoses and treatment; it involves one in some of the most intimate decisions of a patient’s life. This requires a considerable amount of human delicacy and judgment, no less than medical judgment and knowledge. If there is a serious, perhaps life-threatening or life-altering condition, what should one tell the patient, and when? How should one tell the patient? Should one tell the patient? Every situation is complex, but for the most part, patients want to know the truth, however dire it is. But they want to hear it delivered with tact, with indications if not of hope, then at least a sense of how such life as they have left can be lived in the most dignified, fulfilling way.

  Such telling assumes a whole other order of complexity when a patient has a dementia, for here one is intimating not only a death sentence, but one of mental decline, confusion, and, finally, to some degree, loss of self.

  * * *

  —

  THIS BECAME COMPLEX, tragic, with Dr. M. He had been the medical director of a hospital where I worked, and he had retired at the mandatory age of seventy. But ten years later, in 1982, he came back—this time as a patient with moderately advanced Alzheimer’s. He had started to have major difficulties with recent memory, and his wife described him as often confused and disoriented—and sometimes agitated and abusive. She and his doctors had hoped that admitting him to the hospital where he once worked, with surroundings and people he might find familiar, would have a calming and organizing effect on him. I myself and some of the nurses who had worked for Dr. M. were aghast when we heard of this—first that my former chief was now demented, and then that he was to be institutionalized in, of all places, the hospital he had once ruled over as director. This, I thought, would be horribly humiliating, almost an exercise in sadism.

  A year after his admission, I summarized his state in a note for his chart:

  I have the melancholic task of seeing my former friend and colleague, now fallen upon such evil days. He was admitted here just a year ago, with the diagnosis…of Alzheimer’s disease and multi-infarct dementia….

  The first weeks and months here were exceedingly difficult. Dr. M. showed incessant “drive” and agitation, and was put on phenothiazines and Haldol to calm him. The effect of these, even in very small doses, was to cause severe lethargy and parkinsonism—he lost weight, he fell constantly, he became cachectic, looked terminal. With the cessation of such drugs, he has regained his physical health and energy—walks and talks freely, but requires constant attendance (for he would wander off, and is erratic and unpredictable in the extreme). There is striking fluctuation in his mood and mental state—he shows “lucid moments” (or minutes), and returns to his formal, genial personality, but for most of the time is lost in severe disorientation and agitation. Undoubtedly the relation with a devoted attendant is good—and the best we can do. But, unhappily, he is driven and distraught for [much of the time].

  It is difficult to know how much he “realizes,” and this fluctuates profoundly, almost from second to second.

  He enjoys coming to the clinic and yarning of “the old days” with [the nurses]. He seems most at home here, doing this…and at such times may be amazingly coherent, able to write (even wri
te prescriptions!).

  At such moments, when Dr. M. stepped into his prior role as a hospital director, the transformation was amazingly complete, even if brief. It happened so quickly that none of us quite knew how to react, how to handle this unprecedented situation. But these were rare interludes, I noted, in his frenzied, driven life. In his chart, I wrote:

  He is always “on the go,” and for much of the time seems to imagine he is still a doctor here; will speak to other patients not as a fellow patient but as a doctor would, and will look through their charts unless stopped.

  On one occasion, he saw his own chart, said “Charles M.—that’s me,” opened it, saw “Alzheimer’s disease,” and said, “God help me!” and wept.

  Sometimes he calls out, “I want to die….Let me die.”

  Sometimes he fails to recognize Dr. Schwartz, sometimes he fondly calls him “Walter.” And I had a very similar experience this morning: when he was brought into [my office], he was very agitated and driven, would not sit down, let me talk with him [or] examine him. A few minutes later, by chance, when I passed him in the corridor, he instantly recognized me (having forgotten, I think, that he had seen me a few minutes before), called me by name, said, “He’s the best!” and asked me to help him.

  * * *

  —

  MR. Q. WAS ANOTHER PATIENT, less demented than Dr. M., who resided in a nursing home run by the Little Sisters of the Poor where I often worked. He had been employed for many years as the janitor at a boarding school and now found himself in a somewhat similar place: an institutional building with institutional furniture and a great many people coming and going, especially in the daytime, some in authority, and dressed accordingly, others under their guidance; there was also a strict curriculum, with fixed mealtimes and fixed times for getting up and going to bed. So perhaps it was not entirely unexpected that Mr. Q. should imagine that he was still a janitor, still at a school (albeit a school that had undergone some puzzling changes). But if the pupils were sometimes bedridden or elderly, and the staff wore the white habits of a religious order, these were mere details—he never bothered with administrative matters.