The woman struggled to get her 53-year-old husband out of the car and into the just-borrowed wheelchair. She rolled him through the crisp February air to the Emergency Department at Lawrence and Memorial Hospital in New London, Conn. They had driven straight from the neurosurgeon’s office, where the physician assistant was shocked by how weak the man had become, how much worse he was than six weeks earlier when he last saw the patient.
In the E.R., the man lay moaning quietly on the stretcher. His blood pressure was low, his heart rate was high. He could barely move his legs on his own, and when the E.R. doctor lifted each leg and let go, he couldn’t hold them up. The doctors were worried something was compressing the man’s spinal cord. The patient needed an M.R.I. right away.
After the test, the man was given fluids. He hadn’t been eating or drinking much for the past few weeks, his wife told the nurse. The M.R.I. showed wear and tear in his neck and some narrowing of the spinal column in his lower back, but it didn’t seem enough to cause this profound weakness. Even so, the neurosurgeon who reviewed the results thought they should start him on intravenous steroids to bring down any swelling that might not have been seen on the M.R.I.
That night, after his wife went home, the patient, tired and a little confused, could only provide the admitting doctor with a very basic story. His legs had started hurting a few months earlier. It began with a pins-and-needles feeling in his feet that over time moved upward. And he had terrible leg cramps. He couldn’t sleep. He couldn’t work. Then he couldn’t walk. And now he was here.
The doctor found the rest of the history in his chart. Back in September, his primary-care doctor sent him for an M.R.I. and tested him for B12 deficiency and, because this was Connecticut, for Lyme disease. His B12 was low, so she started him on a supplement. He didn’t have Lyme disease. And that M.R.I. showed some osteoarthritis and mild compression, so she sent him to a neurosurgeon. He was given oral steroids and referred for physical therapy. Neither helped.
By December, he was unable to leave the house. He fell several times. By January he was having problems with his memory. He missed appointments; didn’t get ordered lab work. The patient had a long history of drinking, the doctor noted. The previous year, he was found guilty of driving under the influence and had to go to a court-ordered alcohol program. He was drinking less, he told the doctor. But still drinking. He had a drink earlier that day, he admitted. But only one.
Many Treatments, but No Improvement
The lab tests ordered in the E.R. showed some signs of heavy alcohol use. Drinking could cause a serious neuropathy, though usually it was a loss of sensation rather than the profound weakness he had. Alcohol-use disorder has long been associated with severe nutritional deficiencies because of poor food intake, and because heavy drinking can impair nutrient absorption. His vitamin B12 was better; he was taking that at home. But his vitamin B1, also known as thiamine, was undetectable. Both of those deficiencies could cause weakness and the kind of nerve pain he had. The memory issues, too, and the confusion. He was started on vitamin B1 and high-dose intravenous steroids. The vitamin B12 was continued.
Dr. Bishal Khanal was worried when he took over the case on the patient’s 19th day in the hospital. The patient remained unable to walk and was confused. Reviewing the chart, it wasn’t clear that he had improved much with the steroids, the vitamin B12 or the thiamine.
The patient underwent dozens of tests. His thyroid hormones were normal, so were his vitamin B12 and now his B1 too. His spinal fluid was sent to the Mayo Clinic to look for autoimmune diseases that could attack the brain and the nervous system. The results were not back, but his doctors started him on the treatment for an autoimmune issue just in case. He was seen by neurosurgery, by neurology, by gastroenterology, by rehabilitation medicine and by psychiatry. All departments made suggestions, but none had discovered the cause of his weakness or his persistent confusion.
Finally, Khanal went in to meet the patient. The man’s wife was at his bedside, as she had been every day. The patient was not able to lift either leg. His arms were weak and shook so ferociously that he could not drink from a glass. His wrists were almost powerless. His wife was frustrated and worried. He had been in the hospital for so long and still could not get out of bed. Why couldn’t the doctors help him?
Khanal was struck by all the nutritional issues that the man had from his alcohol use. And yet, according to the testing, they all seemed to be getting better. His albumin and prealbumin, which can decrease when a patient is malnourished, had been low when he first got to the hospital. They were improving. Indeed, all his labs were getting better, but the patient was not. What were they missing?
There was another B vitamin that hadn’t been tested for: vitamin B6, an essential component in dozens of bodily functions. It’s found in many foods, so deficiency seemed unlikely, but Khanal thought it was worth checking.
Another possibility came to mind as well: insufficient dietary copper could mimic the symptoms of vitamin B12 deficiency. But this was usually only seen in those with some kind of gastrointestinal disorder. In rare cases, it could be caused by excessive zinc intake. But alcohol use? A quick review of the medical literature showed a handful of case reports of copper deficiency associated with heavy drinking. So maybe. The dietary requirement for this mineral was tiny, but it could cause the kind of profound weakness this patient had. He would check for these two deficiencies and wait for the rest of the results to come back.
The findings of the many studies continued to trickle in. The Mayo Clinic identified no sign of an autoimmune disease. The B6 level that Khanal ordered was low but in the normal range.
The Missing Piece
Finally, after three days, the results of the copper test came back. The patient had only half as much of this vital element as he should. Copper is essential for many of the chemical functions of the body and brain, and deficiency can cause both short- and long-term damage to the frontal lobes, which are involved in thinking and memory storage, and the cerebellum, the coordinating center for both body and brain.
Khanal started the patient on intravenous copper. The results were surprisingly fast. Within a day, the terrible tremor disappeared, and he could drink from a glass. And, after five days, he was able to get out of bed and walk, albeit with a walker and closely followed by a nurse pushing a chair on wheels. His wife cried with joy and relief.
I met the patient and his wife recently. He has been home from the hospital and subsequent rehabilitation for nearly four months. He uses a cane and moves carefully, as if still not quite sure how it’s done. His memory is still poor; it is possible it will never get better. Both copper and thiamine deficiency can cause permanent changes.
In medicine we like to work with the idea of Occam’s razor — that the simplest single explanation is most likely to be right. But there was a 20th-century American doctor, John Bamber Hickam, who offered a counterpoint: that a patient’s symptoms might come from multiple diseases at once rather than from one simple cause. In this case, Hickam’s dictum, as it’s called, was right. The patient had deficiencies of many necessary nutrients. Khanal came up with the one that others had missed, but it was all the deficiencies together that caused the damage.
The patient and his wife have been together since they were teenagers. They tell me there were good years and bad years. His drinking was at the heart of their worst years. He hasn’t had a drink since he entered the hospital and is determined to never drink again. His wife is confident that he will not. They vowed for better or for worse, she told me solemnly. But at least now, she is certain, the worst is over.
Lisa Sanders, M.D., is a contributing writer for the magazine. Her latest book is “Diagnosis: Solving the Most Baffling Medical Mysteries.” If you have a solved case to share, write to her at [email protected].
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