Doctors make assumptions about a case — and those assumptions can sometimes cloud their judgment.The 61-year-old woman lifted the laundry basket, then grimly eyed the steps up from the basement. The climb seemed to get tougher every day. Before she was even halfway up, she could feel her racing heart and hear her ragged, rapid breathing. She gripped the wooden handrail in case she started to feel lightheaded again. Once she made it up to the main floor of her home, she dropped her burden and practically fell into the soft embrace of her living-room sofa.The woman first noticed that she often felt out of breath a few months earlier. She wondered if it was her weight. She liked the way she looked, but suspected that her usual care provider, a much-trusted nurse practitioner with a medical group at Yale School of Medicine, would be happy if she lost a few pounds. Her daughter worried that her shortness of breath could be a result of the Covid infection she had a couple of years earlier. She finally called her P.C.P.’s office when her right leg started to hurt. The combination of shortness of breath and leg pain made her nurse practitioner worry that the patient had a clot in her leg that had broken off and lodged in her lungs. She sent her to get an ultrasound of the leg. There was no clot, which was a relief, but she was still out of breath. Referral to the Long Covid CenterFrom that point on it seemed as if she had a video consultation just about every week. Each visit focused on the newest of her many varied symptoms. One week she was so dizzy it was hard for her to walk. The next week she shared her concerns about her recent weight loss: 10 pounds in just two weeks. Another time she saw the physician who worked with her nurse. As she faced her across the distance of their linked computers, the doctor suggested that the lightheadedness might come from not drinking enough water. Her shortness of breath and rapid heart rate were probably because of a lack of exercise. At the next video visit, her nurse practitioner said she might have POTS — short for postural orthostatic tachycardia syndrome. In this uncommon disorder, patients have a rapid heart rate, or tachycardia, whenever they stand up. It is sometimes seen in patients after they recover from a Covid infection. With every new concern, there were more tests. She had ultrasounds and chest X-rays; an echocardiogram showed that her heart was pumping normally; and something called a Holter monitor, a wearable device that tracks heartbeats for 24 hours, showed only that her heart sometimes beat rapidly. She had an M.R.I. of her brain, a CT scan of her chest and lots and lots of blood tests. After all this, the patient was frustrated and frightened that no one could explain why she suddenly felt so bad in so many ways. She was referred to a neurologist, a cardiologist and Yale’s Long Covid Multidisciplinary Care Center. She was seen first at the Long Covid Center, where I am the medical director. That April morning, she told me that she was out of breath all the time. She had to quit her job as a cashier. Her eyes grew shiny when she described her rapid decline. Her heart and lungs had already been evaluated extensively, and the only abnormality was seen in the Holter-monitor test. Like her nurse practitioner, I wondered if she had developed POTS. Certainly, POTS was something I saw regularly in patients with long Covid. A recent study estimated that up to 14 percent of patients developed POTS after recovering from Covid-19. This disorder can be diagnosed using something called the active-stand test. In this test, the patient’s heart rate and blood pressure are monitored when they are supine and then as they stand in place for 10 minutes. A diagnosis of POTS is made if the blood pressure remains stable while the heart rate increases by at least 30 beats per minute. When the patient was given the test, she became lightheaded and out of breath after only a few minutes, and the test had to be stopped early. Her heart rate had increased — to 140 from 101. POTS is not well understood but is thought to signify an injury to the autonomic nervous system. Normally the act of standing triggers a rapid increase in blood moving from the legs and lower body up to the heart so that it can be redistributed to the upper body and brain. In POTS, that doesn’t happen, and to get enough blood to the brain, the heart must beat faster — usually a lot faster. In this patient’s case, as in many others I’d seen, that increase in heart rate is inadequate and the patient feels lightheaded. POTS often appears after a viral infection. While there are medications that can help, the first line of treatment is to increase the amount of water stored in the body and to use compression garments to help get blood out of the lower extremities back to the heart. I wasn’t sure if all of this patient’s symptoms could be attributed to POTS but thought treating POTS was the right first step. I encouraged her to drink more water and prescribed the needed garments. Two weeks later, when she reported that her heart was still racing, I started her on a medication to slow it down. She returned to the office a couple of weeks after that. Her heart was better, she told me, but she was losing weight: “When I look in the mirror, I barely recognize my face.” Her normally plump, round cheeks looked flat and drawn. She had lost 25 pounds in three months. That stopped me. Weight loss was not a usual symptom of POTS. Had I gotten the diagnosis wrong? Photo illustration by Ina JangAn Essential Step SkippedSuddenly her symptoms took on an entirely different shape. I had been making assumptions about her case based on the fact that the doctors who referred her to our center thought her symptoms were a result of long Covid. But in truth, none of us really knew if she was suffering from long Covid. There is no definitive test that links present symptoms to a Covid infection experienced weeks, months or even years earlier. The first published reports of symptoms that outlasted the viral infection came in April 2020, just months after the virus arrived in the United States. And since then, a wide range of symptoms has emerged. But the links between the symptoms and the hypothesized cause was temporal. There is only the patient’s experience to suggest a connection. But as with so many of the disorders for which there are no definitive tests, this is a diagnosis that can be made only when other possibilities have been ruled out. In seeing this patient, I skipped that essential step. This was a middle-aged woman who had a racing heart, who became short of breath with any exertion, who was rapidly losing weight — a classic presentation of thyroid-hormone overload, a condition known as hyperthyroidism. This tiny gland located in the neck is part of a complex system that controls body metabolism. When too much thyroid hormone is released, the body’s engine revs as if someone had stepped on the gas and not let up. She had all the symptoms of hyperthyroidism, and I had simply not seen it. I sent her to the lab down the hall from my office. Within hours it was clear that her system was flooded with these hormones. I called the patient immediately to explain that, despite the positive active-stand test, she probably did not have POTS and that, instead, her thyroid had gone wild. This is usually a result of an autoimmune disorder known as Graves’ disease, in which antibodies bind to thyroid gland receptors, mistake these normal cells for attacking invaders and trigger a near-continuous release of its hormones. Even before the diagnosis of Graves’ was confirmed, the patient was started on a medication to block hormone production. I have spent the past 20 years writing and thinking about diagnostic errors. And I understand how this one happened. In medicine, most diagnoses are made through a process of recognition. We see something, recognize it and act on what we see. Most of the time we are right. Most of the time. I’ve asked this patient for a photograph to keep on my desk. A reminder, I hope, that the first diagnosis to come to mind can never be the only one considered.As for the patient, she feels much better since starting these medications. Her heart rate is down, and the basement stairs are getting easier. She tells me she stopped losing weight, but she won’t feel as if she is back to her old self until her cheekbones go back into hiding.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 her at Lisa.Sandersmdnyt@gmail.com.

Doctors quickly found the cause of the patient’s excruciating abdominal pain. They had to dig deeper to find what was giving him a peculiar tint.“You are so yellow,” the physician assistant told the 39-year-old man. It was said as a simple statement of fact. In the bright lights of the CityMD Urgent Care center in Ronkonkoma, N.Y., the man could see that this was true; his normally light brown skin now had a distinctly saffron cast to it. You need more than this walk-in center can offer, the P.A. explained. Stony Brook University Hospital wasn’t far away. Would he like her to call an ambulance for him?He could drive himself, he told her, although the thought of climbing back into his car and driving anywhere was unappealing. All he wanted to do was lie down and have someone tell him how he could make this terrible pain in his abdomen stop. Thank goodness for valet parking, he thought as he drove up to the emergency room. He left the key with the attendant and, holding his stomach, made his way to the crowded E.R.He had experienced pain like this in the past, though never this bad. Once or twice a year, he would eat something that didn’t seem to agree with him. He would feel bloated, his stomach tight and achy. Burping sometimes helped. But the pressure would get so bad that he would often make himself throw up to relieve it. The pain came in waves. He would feel a little pressure and know that more was coming. It would ease a bit and then hours later come roaring back, lasting longer. That would continue, each wave more intense than the last, for a day, sometimes two. And once the pressure started, he couldn’t eat. Anything more than water was brutal. Only when the pain stopped could he add broth or juice and build up from that.By the time he was called into the E.R. treatment area, his face and shirt were drenched with sweat. He could barely stand. Eventually he was helped onto a stretcher and placed in a cubicle. A half-dozen people came in, asked him questions, took his blood. He had a CT scan and an ultrasound, and within hours he had an answer: He had stones in his gallbladder. And one of them was stuck in the narrow tube that carries the digestive fluid known as bile from the gallbladder to the small intestine. That blockage was the source of the terrible pain. The stone would probably pass on its own — just as it did in all the painful episodes he had before. If not, it would have to be removed surgically. In any case, he was told, his gallbladder would be removed. He asked the many doctors he saw that night if this explained why he was so yellow. An unsatisfying “maybe” was all the answer he got.The Yellow MatterBy morning, the man was feeling better — the jammed gallstone must have gotten loose and moved on. He was sitting up in bed, reading his phone, when he noticed a small group of doctors collecting outside his door. A young woman gave what he recognized as a description of his own presentation to the emergency room. Then an older doctor began talking about jaundice, the yellowing of the skin and eyes. The color came from a buildup of something known as bilirubin, a breakdown product of red blood cells. Normally there is a constant low level of this dark-colored waste created and disposed of as red blood cells are born and die. But there are diseases that can increase bilirubin levels — either because something happens to block its excretion or because more red blood cells are being broken down, causing more bilirubin to be made. In this patient’s case, the stuck gallstone blocked the flow of bilirubin into the gastrointestinal tract. But that doesn’t usually cause jaundice like this. The whites of a patient’s eyes might be a little yellow — it’s where jaundice is most easily seen — but this man was visibly yellow everywhere. He had far more bilirubin than would be expected in a blocked gallbladder. Our job, he explained to the doctors in training, is to figure out why.“Do you think I’m hemolyzing?” the patient called out from his bed. Silence fell as every face turned toward him. Hemolyzing, they knew, was the destruction of red blood cells. But this wasn’t a word patients usually used. The patient got out of bed and ambled to the doorway. He could see the unasked question in their eyes. He went to medical school, he told the group, though he never went into practice.Dr. Peter Braverman introduced himself and the three doctors in training on the team. Here’s something else interesting, he told the patient and the trainees. If you look at the blood-cell count, you can see that this young man has an anemia — a lower-than-usual number of red blood cells. That’s rare in a man. And the blood cells he does have are very, very small. Usually you see that only with a severe iron deficiency or with some anomaly in the shape of the red blood cells. Normal ones are shaped like SweeTarts candies — disc-shaped, with an indentation on each side. That shape allows the cells maximal flexibility in order to move through the narrowest capillaries in the body. Red blood cells with any other shape are destroyed at a much higher rate. That can give you jaundice, especially if the elimination of the extra bilirubin is blocked. Let’s reach out to the hematology service, the doctor said, to help us figure out the mysteries of this man’s blood.Braverman, meanwhile, was curious. This young man had medical training. What did he make of his yellowed skin and eyes? The patient looked away uncomfortably. Actually, he hadn’t noticed it. During the pandemic, he moved in with his parents and was working from home. He had been quite isolated. Hadn’t been to his office. Hadn’t seen his friends. His parents, who were elderly, hadn’t said a word. And he didn’t look in the mirror much. In past years he noticed that the whites of his eyes sometimes had a yellow tint to them. Based on that, he had diagnosed himself with Gilbert’s syndrome, a benign condition that is caused by not having enough of the enzymes that break down bilirubin. People with Gilbert’s may have a yellowish cast to their eyes, especially during times of physical or emotional stress, when red blood cells are broken down more rapidly. But he never connected the yellow he sometimes saw in the mirror to the bouts of abdominal pains. And he had never been this yellow.Photo illustration by Ina JangStones and SludgeOver the next several days, the yellow in the patient’s skin and eyes faded. He was taken to the operating room. The gallbladder the surgeons removed was filled with dark brown stones and sludge — some of the excess bilirubin accumulated in the sac as pea-size accretions, and the rest continued to the intestines to be eliminated. It’s bilirubin that gives stool its dark color.While still in the hospital, the patient was seen by the hematology team. The small cells weren’t caused by a deficiency in iron. Indeed, he had plenty of iron. Instead, the specialists looked for some inherited abnormality in his red blood cells that caused them to be destroyed at a higher rate. He didn’t have sickle-cell disease. In this disorder, stress causes red blood cells to turn from SweeTarts to crescent moons that become trapped in the circulation and destroyed. Another common cause of the destruction of red blood cells is a deficiency of a protective enzyme called G6PD. Without this enzyme, infections, medications and even some foods can cause red blood cells to hemolyze. Thalassemia was a third possibility. Patients born with this inherited disorder make abnormal blood cells that are often destroyed at a much higher rate. Yet even before the patient left the hospital, his doctors knew he didn’t have any of these common inherited blood diseases.The patient saw the hematology team in its office several weeks later. The specialist sent off a half-dozen more tubes of blood, looking for some of the rare causes of hemolysis. This batch provided an answer: He had hereditary spherocytosis, a disease in which the red blood cells were tiny spheres rather than the usual biconcave discs. This shape makes them much easier to damage as they flow through narrowing blood vessels and other blood pathways, just as a fully inflated balloon is a lot easier to pop than one only half full.The patient asked how he could have inherited the disease. No one else in his very large family had it. Perhaps he was the first to have the mutation, the hematologist suggested. It wasn’t exactly the kind of first the man had imagined for himself. Still, he was glad to finally have an explanation for his episodes of abdominal pain. And really glad to know that now that he didn’t have a gallbladder, he wouldn’t have another.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 her at Lisa.Sandersmdnyt@gmail.com.

She constantly felt the need to clear her throat. Then she started to feel winded on stairs. A flurry of tests narrowed down the cause.One of the first things she noticed was how she had to keep clearing her throat. Everyone does it every now and then, but for her, a healthy woman in her early 70s, it had become constant. Her husband never complained. He was a surgeon, and when the throat-clearing started, he showed her a few breathing exercises. Those were sometimes helpful, but eventually she would be ahem-ing every few minutes again. Even more annoying was that any exertion could trigger a strange, harsh-sounding wheeze. Even when she was on the phone, she often muted herself so friends and family wouldn’t worry. Her primary-care doctor wasn’t worried. Her lungs were clear; her oxygen saturation was fine. She saw a cardiologist, who pronounced her heart to be in good shape after a vigorous stress test. Despite the reassurance, she noticed that she was getting winded more easily. In Europe with her granddaughter, she walked 20,000 steps a day on the mostly flat streets of Paris, but the hilly cobblestones of Montmartre left her huffing and puffing. She knew she had to figure this out. But when she got back to her home in Cupertino, Calif., Covid hit, and everything shut down. During that time, the stairs in her home became her measure. For decades, she went up and down those steps many times a day, no problem. She had become used to the harsh wheeze the stairs seemed to trigger, but now she felt out of breath by the time she reached the top. Then she had to stop halfway up. Then after just a few steps. Finally, when the pandemic eased after a terrible year and a half, she saw her primary-care doctor and then a bunch of specialists. Her lungs sounded clear, and a chest X-ray was normal. Was this asthma, or some kind of allergy? A variety of inhalers and an antihistamine were ineffective; an examination of her nose and throat with a tiny scope found nothing. A CT scan of her lungs wasn’t totally normal: She had a few little nodules, and so seven months later she had another scan to see if any of the tiny dots had changed. They hadn’t — probably just scars from some past infection. It was discouraging to hear that everything was fine and at the same time know that it wasn’t. The doctors didn’t know what else to do, and neither did the patient. Her husband asked his colleagues. He called an old friend, Dr. James Wolfe, in nearby San Jose. Wolfe was a lung doctor as well as an allergy specialist. Even though the antihistamines hadn’t helped, maybe allergies were playing a role. Photo illustration by Ina JangSomething Other Than a WheezeWeeks later, the patient and her husband sat in Wolfe’s exam room. As they waited for the specialist, the husband said to his wife: Can you jump up and down a few times so the doctor can hear what you sound like when you are a little out of breath? It worked. As Wolfe greeted his old friend, he noticed the patient’s noisy breathing. But it was obvious to him that this wasn’t a typical wheeze. Those usually occur during exhalation. This woman’s breath was noisiest when she inhaled — a type of wheeze known as stridor. This is an important observation, because the causes of stridor are different from other types of wheezing. Stridor is usually caused by blockages in the upper airways — from vocal-cord dysfunction or swollen tissues in the nose or throat. That was puzzling; her upper airways had already been examined. They were fine.Wolfe had the patient do a second breathing test when she arrived. The first, done a year earlier, was completely normal. This one wasn’t. The changes were subtle but real. The amount of air she could get out in a forced exhalation was less than it was when she was tested the year before.Could this be some tough form of asthma, considering that the usual medications hadn’t helped? Or was this some kind of slow-growing lung infection? There is a bacterium, a distant cousin of tuberculosis, called mycobacterium avium complex (MAC), which can cause coughing, shortness of breath and phlegm production. It is rare but is most often seen in older women. It’s thought to be caused, at least in part, by a woman’s reluctance to cough and clear mucus and other secretions from her lungs and airways. It’s called Lady Windermere syndrome, after a character in an Oscar Wilde play. Lady Windermere is a very proper young woman of the Victorian era who presumably would be too well behaved to cough or show other signs of illness. The nodules in the patient’s lungs that showed up on her CT scans could be the earliest sign of such an infection.Wolfe ordered a series of tests to look for each of these disorders. He also ordered another CT scan of her lungs — her third — to see if the nodules had changed in the months since her last scan. Flipping Through CT ImagesDr. Emily Tsai, a radiologist who specialized in imaging of the chest at Stanford University School of Medicine, sat in a darkened room looking through the more than 300 images of the patient’s new CT scan. Although you could look at each image separately, it is often more useful to view them sequentially, like a flipbook in which drawings turn into moving pictures. In this way the radiologist can take a three-dimensional tour through the examined chest, following the blood vessels and airways as they appear, progress and end in this animated show. Tsai had developed her own system: First she would look through the image as a whole, seeking obvious abnormalities and getting the lay of the land. She compared the newest views with the earlier images. Then she would focus on the part of the lung where there were reported or expected abnormalities. In this woman’s case, she looked where the reported nodules had been located. There was a little scarring — where the narrow treelike branches of the airways got stretched out and baggy in what was called bronchiectasis. That could certainly go along with a diagnosis of MAC infection. Then she took another careful look at all the other parts of the chest. In images like these, filled with so much information, a radiologist has to review the images as closely as possible. No one can see everything. Maybe artificial intelligence will get there one day. But she tried to see what was there.As she scrolled to the very top of the image, she saw something that seemed a little abnormal. The trachea, the breathing tube that connects the upper airways of nose and mouth to the lower airways of the lungs, seemed to be strangely narrow near the top. The narrowing was less than a centimeter long before it widened out to the normal diameter. Tsai found the same narrowing in the other CTs and reviewed the reports to see what previous radiologists made of this finding. Neither mentioned it at all, perhaps because it looked like a tiny puddle of secretions. The key was that it was the same in all three exams. Secretions move around. This narrowing, whatever the cause, did not. Tsai wasn’t sure what to make of it, but in her report she suggested that it could be contributing to the patient’s symptoms. When Wolfe saw the radiologist’s report, he realized that this narrowing of the trachea could be the cause of all of the patient’s symptoms. How had it happened? She had never needed a breathing tube placed in her trachea during surgery or a serious illness — that was the most common cause of this type of unusual finding. Wolfe ordered further tests to look for possible infections or inflammatory causes of the narrowing. All were unrevealing. It wasn’t MAC or any of the other causes Wolfe could think of or test for. Ruling out everything gave him her diagnosis: She had idiopathic subglottic stenosis. Idiopathic meant that the cause was unknown. Subglottic identified the location in the trachea, just below the vocal cords. It is a rare and poorly understood disorder seen almost exclusively in middle-aged women. Because her narrowing was causing her to be short of breath, the stricture needed to be opened. Wolfe sent her to a surgeon who used a balloon to widen the narrowed tract. The patient told me that she could feel the difference as soon as she woke up. And in the eight months since her surgery, she has regained all that she lost. Within days, she was able to run up and down her hallway stairs once more.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 her at Lisa.Sandersmdnyt@gmail.com.

His vital signs were normal. He didn’t have a fever. A slew of tests couldn’t find the cause. Then a locker-room conversation between doctors led to the diagnosis.“It’s happening,” the 58-year-old man said quietly. Dr. Mark Chelmowski looked over to observe his patient. He was leaning forward, elbows on table, head propped up on his hands. Beads of sweat suddenly appeared on the man’s brow. More popped up on his cheeks, then his jaw. Rivulets ran down the contours of his face, then dripped off his chin onto the table. The man’s eyes were closed. He almost seemed asleep. Chelmowski said his name. “Yes, doctor” was the only response the normally chatty man gave. It was as if he were somehow distracted by the profound sweating. The patient’s vital signs were normal. He didn’t have a fever. His blood pressure and heart rate were normal. Throughout the exam, the patient sat quietly sweating. The collar, front and back of his shirt darkened. Then, as abruptly as it started, it was over. He opened his eyes and looked at Chelmowski. The patient could see the surprise in his doctor’s face. Chelmowski knew about his episodes of sweating — the two of them had been trying to figure them out for the past five months — but he had not yet witnessed one. The first time it happened, the patient was in his car on the way to the gym when suddenly he felt intensely hot. It was a bright July day in the Milwaukee area and seasonably warm. But this heat felt as if it came from inside his body. A vague prickling sensation spread down his face and neck to his chest and back. His heart seemed to speed up and then — pow — he was drenched in sweat. He turned the car around and headed home. He was describing the strange event to his partner when it happened again. And again. Each episode lasted only a couple of minutes, but it was strange. The sweating was so excessive. After a fourth episode, the patient’s partner insisted they go to the emergency room. He had another bout in front of the E.R. doctor, who immediately admitted him to the hospital. He was worried the patient might be having a heart attack. Profuse sweating often accompanies myocardial infarctions, the doctor told him. But it wasn’t his heart. He was discharged the next day and encouraged to follow up with his primary-care doctor. Chelmowski had been trying to figure out these strange episodes ever since. He had never seen anything like it, he told the patient after finally witnessing the strange sweating event. And he really wasn’t sure where else to look. When he saw the patient a week after that first episode, his exam was completely unremarkable. So were the tests that the doctor ordered. His thyroid hormones were normal. He didn’t have an infection. His inflammatory markers were not elevated. And he seemed fine. Whatever it was, the doctor figured, it was over. Then, a month later, it happened again: a half day of intense episodes of drenching sweats and strange distraction, one after the other, each lasting only a few minutes. From that point, the episodes recurred every three to five weeks. A Trip to the TropicsThe pattern made the strange symptom seem even stranger. The patient was in good shape. He ate a healthy diet and exercised regularly. The only medication he took was an acid reducer for his heartburn. He was almost never sick.Chelmowski spent hours trying to figure out what was going on. The patient had traveled to the tropics earlier that year. Repeated tests for malaria were negative. It wasn’t H.I.V. The doctor referred him to an endocrinologist. Could this be a pheochromocytoma — a usually benign tumor that causes the adrenal glands to produce too much of the fight-or-flight hormones? Carcinoid tumors live in the gut and produce a variety of hormones. One key symptom of this tumor is flushing and sweating. He was tested for these abnormalities along with other hormonal disorders. Nothing. The infectious-disease doctors who saw him couldn’t find an infection. A cardiologist ordered echocardiograms and EKGs. Normal. A portable monitor found no abnormal heart rhythms over the course of 30 days. Chelmowski looked for cancers. They can often cause odd symptoms like this. But he found nothing. The patient saw a rheumatologist and a neurologist. They didn’t find anything, either. Chelmowski searched the medical literature for possibilities. He did his own version of crowdsourcing — asking every doctor he ran across if they had any patients with these symptoms. No one had any answers. Chelmowski was stumped and frustrated. What was he missing? He referred the patient to the Mayo Clinic in Rochester, Minn. Maybe they could figure this out. The patient spent two full days in Rochester. He was poked, prodded, imaged, stuck and questioned. Finally, they came up with an answer: Although his testosterone level was in the normal range, perhaps it was less than he was used to. Maybe this was a relative hormonal deficiency akin to a woman’s menopause, a reaction to the natural reduction of sex hormones because of aging. They recommended testosterone-replacement therapy. The patient was skeptical but applied the testosterone gel as directed. He used it for months. It didn’t help. Photo illustration by Ina JangLocker-Room Consultation Chelmowski was beginning to worry that he was never going to figure it out. Early one morning, at his usual spin class, he found himself on a bike next to an old friend, George Morris, who was a neurologist specializing in seizure disorders. Could these weird episodes be seizures? They weren’t like any seizures Chelmowski had ever heard of, but who knows? In the locker room, he approached Morris. “Have you ever heard of seizures characterized by profuse sweating?” he asked. He outlined the patient’s story. Morris nodded his head as he listened. Yes, he had several patients who sweated like this. Chelmowski should send the patient to his clinic to be tested. A few weeks later the patient went to the epilepsy center at Aurora St. Luke’s Medical Center, where Morris was medical director. A 20-minute electroencephalogram was normal. If these were seizures, Morris told him, there was a good chance that they would show up on the EEG only when he was having one. They arranged for the patient to return before his next expected day of sweating. It took about an hour for the electrodes to be placed onto his head for the EEG. He could almost cover the whole array with a baseball cap. He didn’t usually wear one, but it was better than walking around with a head full of wires for all to see. Every morning a technician would come to his house to download the data. He was supposed to be hooked up for seven days, but when no sweating episodes happened, they gave him another weekend. And finally, his long-awaited day of sweating occurred. A couple of days later he got a call. These were seizures. They originated on the left side of his brain, just behind the ear, in what is known as the temporal lobe. A seizure is an episode of abnormal brain activity, and the temporal lobe is in close communication with the autonomic nervous system, which can trigger sweating. Days later, he went back to the center to see Morris and start medications to stop the seizures. He asked the doctor why the episodes came every month. Morris just shook his head. Some seizures have this kind of rhythm. They can be any number of days apart, but a 20-to-30-day cycle is the most common. No one is sure why. It took a while for the patient to get on the right medications at the right dose, but once on it, his seizures stopped. He hasn’t had one in nearly five years. The patient doesn’t know why he started getting seizures at age 58, although he wonders whether it’s linked to a car accident he was in when he was 10 or 11. He was riding in the front seat in the days before seatbelts and smashed his head on the steering wheel. Maybe, Morris told me. That kind of injury can cause seizures many years later. The injured neurons cause abnormalities in surrounding brain cells, which may, eventually, trigger the abnormal activity that results in a seizure. But epilepsy, as recurring seizures are called, often starts in late middle age. Morris attributes it to cerebrovascular disease — what others call ministrokes.This patient isn’t buying it. He still traces it all back to a head-on collision resulting in a close encounter with a hard plastic steering wheel.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 her at Lisa.Sandersmdnyt@gmail.com.

A few weeks after she twisted her ankle, the girl’s foot kept getting worse. Her hand movements cued the doctor to a mysterious disease.The 9-year-old girl was strangely quiet throughout the meal. It was so uncharacteristic that in retrospect her father wasn’t sure why he didn’t notice. But he didn’t — until she started to scream. As tears ran down the girl’s face, she pointed to her foot, which was nestled in her lap.The man scooped his daughter into his arms and hurried out to his car. The crying stopped by the time they reached the urgent-care center near their hotel in Miami Beach, but her foot was still too painful to walk on.In the exam room, the father finally got a good look at his daughter’s foot. He was surprised: It looked completely normal. An E.R. doctor introduced herself and examined the limb. It looked OK to her too, and when the X-ray didn’t show anything, the doctor shrugged. If it keeps hurting, you should follow up with her doctor, she said.The father was baffled. The girl had twisted her ankle a few weeks earlier, but she was swimming and playing in the hotel pool most of the afternoon — enjoying the sun in this midwinter break before heading back to their home in New York City. But that night of pain was only the beginning. His youngest was a tough kid, but after the trip to Florida she complained about her ankle and foot just about every day. She had to sit out most of basketball season. She said it hurt too much to run.She had sprained that ankle several times over the past couple of years. Her doctors blamed weak ligaments and a sports-heavy schedule. They were an active family and recognized that injuries were just part of sports. But this was different. It seemed as if her ankle never got better after that last injury. Over the next few months, she saw a couple of orthopedists at the Hospital for Special Surgery. One ordered an M.R.I. of the ankle. That study was its own kind of nightmare. Holding her foot in the correct position was painful, the girl told them. And holding it still was practically impossible. Her foot had developed a tendency to roll to the side so that the arch and sole faced inward rather than down. And her toes were constantly in motion.The M.R.I. was unremarkable. Physical therapy helped the stiffness but didn’t straighten out her foot. A cortisone shot did nothing. Same with an ankle brace. How could all this grow out of a sprain, the parents asked each other. A rheumatologist was certain that this was juvenile rheumatoid arthritis. The blood tests said otherwise. As spring arrived, the young girl started using crutches to get around. Any weight-bearing was excruciating.Finally one evening, out of a sense of desperation, the father reached out to a high school friend, Joshua Hyman, who was now a pediatric orthopedic surgeon at NewYork-Presbyterian Morgan Stanley Children’s Hospital. He described his daughter’s pain and the strange stiffness that seemed to keep her foot on its side. There was a thoughtful silence on the phone, and then Hyman asked his friend if he was able to move his daughter’s foot — able to put it in a more normal position? He could, the father answered, but it felt as if the foot were fighting him. And as soon as the pressure was released, it would slowly turn back to its side. That’s how it felt best, his daughter told him.There was another pause. “Has anyone mentioned something called dystonia to you?” Hyman asked.A Wrong Message?Dystonia is a movement disorder characterized by persistent or intermittent muscle contractions, which cause abnormal, often repetitive movements or positions, Hyman explained. It can affect any part of the body, and in some cases the entire body. It’s a problem with the brain and the nerves. They send the wrong message to the muscles. There are lots of possible causes, Hyman added: medications, infections, brain injuries, a handful of inherited diseases. Dystonia? the father asked. He wasn’t sure he’d ever heard the word. How did she get this? Why did she get this? Is there a treatment? Hyman was sympathetic but couldn’t answer his friend’s many questions. For that they needed a neurologist — probably one specializing in movement disorders.It was late spring when the family got in to see Dr. Steven Frucht, director of the Fresco Institute for Parkinson’s and Movement Disorders at N.Y.U. Langone Health. As soon as he entered the exam room, Frucht noticed that the girl’s feet were asymmetric. She was sitting on a chair that was too tall for her feet to reach the floor, so they just hung down, at rest. The right foot was straight, as expected. The left pointed inward, toward the right, at a very unnatural angle. Frucht introduced himself and listened as the girl and her parents described her months of ankle pain.He asked if she could put her feet flat on the floor. It was easy to do with the right foot, but the left seemed to curve inward so that only the outer edge of the foot rested on the ground. And the big toe on the left foot moved up and down constantly. The toes on the right were still. “Why are your toes moving?” Frucht asked. “Because it’s uncomfortable,” the girl replied.Photo illustration by Ina JangRapping Her Knuckles on the TableFrucht asked if she had any problems with her hands. “Not really,” the girl answered. “Except I always get cramps when I write.” He gave her a pen and paper and asked her to write something for him. She had been writing for only a few seconds when she put down the pen and rapped her knuckles on the table. She then picked up the pen and started writing again. “Why did you do that?” Frucht asked. It feels better, she said.Frucht shared with the family the diagnosis he’d been considering since he first saw the child. There is a form of dystonia that, while rare, is the most common form of inherited limb dystonia seen in people of Ashkenazi Jewish descent. It is called DYT-TOR1A — named for the gene that is abnormal in this disease.“Whom could she have inherited it from?” the girl’s father asked. Neither parent nor anyone in either family had this problem. Frucht nodded; it is one of the mysteries of this disease. Only one parent has to have the gene to pass it on. Yet most people with this abnormal gene never develop the disease. No one understands why. Her father asked if it was her sports injuries that set her up for this. Probably not, the doctor replied, although there is still so much we don’t know. What we do know, he told them, is that this disease is often progressive. It had spread from her right hand to her left foot. And it may spread farther. Of course, they would need to do a test to see if she had this abnormality. Results would take about a week.When the test came back positive, the doctor started the girl on a drug called Artane, which blocks some of the brain’s abnormal signals to the body. As the dose was increased, the girl and her parents could see the difference. Her walk wasn’t completely normal, but it was much better — so much better that she was able to go to summer camp.But she had to keep increasing the dose of the medication. And by midfall she was starting to have side effects. Her performance in school, which had always been excellent, started to suffer. Frucht had told the family that there was another kind of treatment for this disorder, though he didn’t recommend it for younger children. It was something called deep brain stimulation. A small electrode could be implanted in the part of the brain where movement originates. Tiny electrical pulses would be generated at the site of the implant, and these pulses could block most of the abnormal signals that were driving the girl’s muscles to contract and jump. The parents were worried by the prospect of permanently implanting something in their daughter’s brain, but were even more worried by the progressive nature of this disease. The girl was excited by the prospect of not having to take a pill three times a day, but when one surgeon they saw said she would have to shave her head for the surgery, she immediately said no. She was quite proud of her long dark hair. Her parents kept looking. Finally they found a surgeon who had a lot of experience and would shave only a small patch of scalp.It took awhile, but the surgery has been life-changing. Or perhaps, the family would say, life-normalizing. Because she’s back: She’s back on the basketball court, back to her good grades. She still has her head of beautiful dark hair; and even the tiny patch that was shaved for the surgery is back.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 her at Lisa.Sandersmdnyt@gmail.com.

An M.R.I. ruled out the most common cause of sciatica. Then her rheumatologist asked about her asthma.The 56-year-old woman eased herself into her desk chair. Sitting was wildly uncomfortable these days. She clicked on the link to her Facebook page and began her post: “I’ve been struggling mightily for the past few weeks with sciatica, which is excruciating leg pain caused by a pinched or irritated nerve.” It hurt to stand; it hurt even more to sit — the weight of her body was torture on her thighs. The only times she was mostly pain free were when she was lying down and when she was walking. She was a journalist, and for the past several weeks she had to do all her reporting and writing from her couch. She’d seen her doctor, who gave her a muscle relaxer, and her chiropractor, who adjusted her back. Neither provided any relief. The patient had been healthy her entire life. Then at 50 she wrestled with an ugly bout of colon cancer. She recovered completely with lots of help from surgery and chemotherapy. Four years later, she developed severe asthma out of the blue. A thoughtful pulmonologist helped her get that under control, but she hadn’t felt well since. It was as if she had crossed some threshold. She got these strange bouts of aches and pains, occasional numbness and weakness that lasted for days. Lymph nodes blew up to a painful size, then disappeared. Now this terrible leg pain. Strangely, her back didn’t hurt at all, but her legs, especially the left, were killing her. It was her husband who gave her pain a name — sciatica. But he didn’t know how to fix it. Finally, she decided to ask the crowd — or at least her crowd of Facebook friends. “Any suggestions out there from people who have gone through this?” Within hours she got more than 60 responses. Most offered sympathy, heartfelt and welcome but not helpful. Finally, a Facebook friend who was married to a physical therapist messaged her: See my husband. He can tell you right away if you need an M.R.I. or if P.T. is likely to be enough. Nothing on the M.R.I.She saw her friend’s husband, who gave her some exercises and told her that if they helped, great, but if they didn’t, she probably needed an M.R.I. She was religiously adherent to the prescribed regimen, but the pain persisted. The sciatic nerve is the largest nerve in the body, and the irritation of that nerve that causes the pain better known as sciatica is usually a result of pressure from the bony spinal column. Those points can often be seen on an M.R.I. But not, as it turned out, on her M.R.I. And that was why, three days later, she made her way to the office of Dr. Dustin Nowacek, a neurologist at Bronson Methodist Hospital in Kalamazoo, Mich. The patient detailed her weeks of pain and weakness. Reclining was OK; walking was mostly painless, though she tired out much too quickly. But just about anything else — especially sitting or standing still — was excruciating. Nowacek noted that the patient limped as she moved from the chair to the examination table. On exam, her left foot was clearly weaker than the right. Indeed, she was unable to keep her left foot pointed up when he applied any downward pressure. And on the right, the foot was strong, but her big toe was not. She couldn’t keep it pointed up when he pressed on it with his thumb. When the doctor tapped the Achilles’ tendon on her right leg, the foot twitched in the expected response. But on the left side, nothing: no reflex movement at all. She was a little alarmed when the doctor pulled out a safety pin and explained that he was going to poke her with it to check her ability to feel pain. Oh, she could feel pain, she assured him. And she could feel the sharp tip of the point everywhere — until he pricked the top of her left foot. There she felt nothing. This kind of nerve injury, which affects both the ability to feel and the ability to move, can have many causes. It was patchy rather than symmetrical, which narrowed the possibilities. Could it be caused by her cancer, back after six years? It seemed unlikely. Thyroid disease was possible, but her symptoms didn’t really fit. This was more likely to be some type of infection: Lyme disease, or H.I.V. or hepatitis. Autoimmune diseases could do this as well. Nowacek sent off a slew of blood tests to look for all of these.Photo illustration by Ina JangThe results trickled in. Her thyroid was normal. It wasn’t H.I.V. or Lyme disease, or any of the usual types of hepatitis. Indeed, the only abnormalities were those suggestive of some kind of autoimmune disease. He had no idea which, so he referred her to a rheumatologist in his practice, Dr. Lakshmi Kocharla. As her physician assistant interviewed the patient, Kocharla carefully reviewed her records and test results. This kind of neuropathy was not uncommon in autoimmune disorders. Sjogren’s syndrome and lupus were probably the most common, but there were others. She would have to keep an open mind and look for other symptoms that might narrow the field. These kinds of mysteries were one of the great pleasures of working in rheumatology. The P.A. summarized her findings, and Kocharla entered the exam room and introduced herself to the middle-aged woman and her husband. She’d heard about the painful legs, Kocharla began, but what else has been going on? So much! She had aches and pains everywhere, and she’d lost more than 20 pounds over the past few months. Maybe the pain had stolen her appetite, but she hadn’t really felt well since she developed asthma two years earlier. That seemed to get the rheumatologist’s attention — which surprised the patient. She had told many doctors about her out-of-the-blue asthma, but none seemed to think it was important. Until now. A New List of Symptoms“Hang on a second,” Kocharla said, after hearing this part of the story. She turned to her laptop computer and typed something in it. Then she passed it to the patient. “Do any of these symptoms seem familiar?” she asked. The patient looked through the list. Fatigue: Sure, but who isn’t tired? Weight loss: check. Swollen lymph nodes: check. Muscle pain: check.And she had the asthma and the numbness and weakness in her left foot and right big toe. “I think you have something called eosinophilic granulomatosis with polyangiitis,” Kocharla said. E.G.P.A. was formerly called Churg-Strauss syndrome for the two physicians, Jacob Churg and Lotte Strauss, who first described the condition in 1951. The disease is linked to an elevated level of white blood cells called eosinophils — the cells that respond in allergic reactions. Somehow these cells become involved in the destruction of small blood vessels all over the body. That’s what causes the numbness and the loss of strength and reflexes. These cells can lead an attack on blood vessels anywhere in the body. It is not clear what triggers this disorder, but it is a destructive, sometimes deadly, disease.Kocharla checked the patient’s blood count. Indeed, her eosinophil count was quite high — eight times the level normally seen. The rheumatologist had never seen this disease in a patient before but had certainly learned about it in her fellowship. It would take a biopsy to confirm the diagnosis, but doing that could permanently damage the already-injured nerve. This patient fit nearly all the diagnostic criteria. She started the patient on a high dose of prednisone to weaken the white-cell-led attack. But because she had never seen a patient with E.G.P.A., she wanted the diagnosis confirmed by someone with more experience: She sent the patient to the Mayo Clinic in Rochester, Minn., to get a second opinion. Even before the patient saw the doctors at Mayo, she had no doubt that Kocharla had been right. After just a week on the steroids she felt great. The pain was gone. She could sit and stand. The level of eosinophils dropped to normal. She could go back to work. The rheumatologist at Mayo had seen many cases of E.G.P.A. before and agreed with Kocharla’s diagnosis. They started her on a second immune-suppressing medication. Following her instincts as a reporter, the patient began to read up on the disease. One article suggested that walking can help control this and other autoimmune diseases, so the patient started taking walks. She averages six to seven miles a day. It has allowed her doctors to lower her medication doses, and she says that even though she is sick — in a very real way sicker than she has ever been — she has never felt healthier.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 her at Lisa.Sandersmdnyt@gmail.com.

At the E.R., the patient learned his blood wasn’t clotting. His mother had the same condition — but the trigger turned out to be a surprise.“Hey, come here,” the 19-year-old man called out to his girlfriend. “This isn’t right.” Although it was nearly 2 a.m., the young woman jumped out of bed and hurried to the bathroom. Her partner had been sick on and off for the past few weeks, and they were both too worried to sleep. The water in the bowl was a deep red — the color of cranberry juice. It looked like pure blood when it came out, the young man told her. “You should go to the emergency room,” the girlfriend urged. Not yet, he said. He would rather get a little sleep and call his mother in the morning. She had something like this several years before.The next morning, his mother agreed that he should go to the emergency room, and so the couple drove to the Yale New Haven Hospital. It was a Wednesday morning, and the place was quiet. He explained the bloody urine and was immediately brought back to be evaluated. He didn’t feel sick, but he was worried.The previous night he noticed a strange rash on his arms and legs, he explained to the physician assistant in the E.R. Tiny red dots. They didn’t hurt or itch — just a bunch of flat dots, like freckles, only red. He immediately went to the internet. The specks, he learned, were called petechiae, from a 17th-century Italian word for freckles. Each dot marks the spot where a tiny bit of blood has been deposited under the skin. It usually suggests an abnormally low level of a blood cell type known as platelets. These tiny cell fragments are the first step in creating a clot after an injury. His mother had a platelet problem, he told the physician assistant, and now he thought maybe he did, too.The young woman looked closely at the dots that covered his arms and legs; he was right — they were petechiae. There were other signs that his platelets were low: He had a blood blister on his tongue and a scattering of bloody spots on the inside of his cheek. And of course, he came in because of bloody urine.In Danger of Bleeding to DeathThe blood tests proved the patient right. His platelets were scarily low. He had a platelet count of 2 — that means he had two thousand platelets per microliter of blood. Normal is 150 to just over 400. With so few platelets, the young man was in danger of bleeding to death if he were injured. He was admitted to the hospital for treatment and observation.A hematologist called to the emergency department diagnosed the young man with a disorder known as immune thrombocytopenia (ITP). This is a somewhat mysterious disorder in which a patient’s own immune system destroys completely normal platelets. The cause is often not found. But just over a third of the time, the disorder can be linked to an infection or other disease process that somehow triggers the body’s antibodies to attack these essential clotting components.In either case, the first step is to stop the destruction of the platelets. The patient was given intravenous immunoglobulin while he was still in the E.D. This treatment is made up of antibodies taken from thousands of blood donors. After 40 years of use, it’s still not clear exactly how it works, but these donated antibodies significantly increase platelet counts in most patients with ITP.Dr. Emily Fishman, the intern assigned to care for the patient in the hospital, met the young man when he finally came to the floor. His story, he told her, actually started nearly a month before the rash began to dot his arms and legs. He caught what seemed like a bad cold. He tested himself for Covid-19: negative. And he started to feel better after just a couple of days. But even as he began to recover, he noticed a lump on the left side of his neck. At first it was just a little tender. But soon it became big and tender. It was as if he had a marshmallow buried under his skin. It got so big it scared him. That was the first time he went to the E.D. A CT scan showed what looked like an inflamed lymph node. A test for mononucleosis was negative, so they sent him home after arranging for him to follow up with an ear, nose and throat doctor.Over the next several days, the mass on his neck stopped hurting and then started to shrink. But while his neck felt better, the rest of him felt worse. He was feverish, sweaty and tired. He had no appetite. He considered going back to the E.D. but didn’t feel quite that sick. And after a few days, he felt fine again. That’s when he saw the rash.Photo illustration by Ina JangA Rash of Little ScabsFishman listened to the young man’s story and then examined him. The lump on his neck was obvious. She had seen it from the doorway. But it wasn’t tender and moved easily, the way lymph nodes are supposed to. The rash was also easily seen, but on his arms she noticed something different. “What’s this?” she asked, pointing to some dots that looked like tiny scabs. That’s from my cats, the patient replied. They had four at home. They liked to play and sometimes left marks.After the exam, Fishman excused herself and went out to look for the senior resident she was working with, Dr. Neeharika Namineni. The resident had also seen the patient and reviewed his records. Fishman described what she found and went over the test results from the E.D. His thyroid was normal. He didn’t have antibodies for Lyme or the other tick-borne diseases frequently seen in the Northeast, anaplasmosis and babesiosis. He didn’t have any antibodies for H.I.V. Fishman paused. Still, he could have early H.I.V., at the stage before antibodies are present. It takes four to six weeks to develop a measurable number of antibodies to most infections. Moreover, an acute H.I.V. infection can start with a fever and a rash. So first she would like to send off a test to look for the H.I.V. itself, to make sure he wasn’t in the earliest stages of that infection. He also had these cat scratches. Could this be cat-scratch fever or toxoplasmosis? Each of those diseases can be transmitted from cats to humans through scratches; each can cause a febrile illness and enlarged lymph nodes. Finally, could this be evidence of a hidden cancer — maybe a testicular cancer — that had spread to his lymph nodes?Namineni thought infection more likely, but certainly cancer was possible. Fishman added tests for these pathogens to their orders. If all the tests came back negative, they would look for a cancer.The next morning they met with the attending for the patient, Dr. Lloyd Friedman. Again Fishman described the patient and her thoughts. Friedman’s eyes lit up when the young woman mentioned the cat scratches. “I’m betting on cat-scratch fever,” he announced enthusiastically once she finished her presentation. Friedman wondered aloud if that infection can cause ITP. A quick search of the internet turned up a single case report. So it was uncommon but still possible. Friedman doubled down. The scratches, the fever, the hugely swollen lymph node: This felt to him like cat-scratch fever.The patient got several doses of intravenous immunoglobulin over the next few days. It did its job — his platelet count began to inch back toward normal, going from 2 to 6 to 15 to 30 to 60. The patient hadn’t felt sick since he got to the hospital, and the blood in his urine and the sores in his mouth cleared up after the first dose of immunoglobulin.With his platelet counts improving — though still far from normal — the patient was safe (and eager) to leave the hospital. Even after he left, Fishman monitored the labs for results. It wasn’t toxoplasmosis. It wasn’t acute H.I.V. Finally, they got their answer: He had cat-scratch fever, an infection caused by a bacterium called Bartonella henselae. By then the patient’s symptoms were long gone. Even the swollen lymph node was barely visible.A few weeks later, a test revealed that the young man’s platelets were back to normal. He still wonders if there is a genetic connection from his mother involved in all this. She has ITP that has lasted for years. She has to get infusions of immunoglobulin when her platelets drop. Was it just a coincidence that he got this, too? It’s a question for his mother’s hematologist. But he thinks it’s kind of cool that it’s all in the family.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 her at Lisa.Sandersmdnyt@gmail.com.

The attending physician, a doctor for 45 years, had never seen the obscure problem causing these symptoms.The 69-year-old man rose from his desk at the guard station in the front hall of the Veterans Administration Medical Center in Birmingham, Ala. He usually patrolled the entrance to the busy clinic once or twice an hour. This time, he didn’t take more than a dozen steps into the humid spring warmth before he felt the familiar symptoms he’d come to dread. His vision blurred. And he was lightheaded, but at the same time, he could sense his legs trembling as if he weighed much more than usual. He leaned against the cool brick wall but knew from experience he wouldn’t stay upright for long. He pulled out the radio at his belt and called for help.Within moments he was in a wheelchair, heading for the emergency department. The man was embarrassed by his transient helplessness, even though it had happened many times before. He was supposed to be assisting those who came to the V.A. for their care. Instead, he was the one needing help.In the E.D., the nurse confirmed what he already knew — he had what’s called orthostatic hypotension (O.H.). When his blood pressure was measured while lying flat, it was normal. But it plunged when he sat up. And when the nurse helped him to his feet, it dropped so low he almost fainted. This had been a problem for several years, off and on, but recently, it had become much worse. He ended up in the E.D. a half-​dozen times these past few months. His doctors advised him to drink more water. He did. And he tried to wear the compression stockings he was prescribed. It was hard because they were hot, and when he wore shorts, he felt ridiculous. He tried to remember to get up slowly. That was the only thing that really helped.Orthostatic hypotension occurs when inadequate blood gets to the brain because of a change in position. Normally, sitting or standing will signal the blood vessels in the legs and lower body to constrict, sending blood upward to the heart and ultimately to the brain. That change also tells the heart to beat more rapidly to help the blood get to the brain faster. Dehydration is a common cause of a positional drop in blood pressure. The blood vessels can’t constrict enough to send the blood to where it’s needed because there’s just not enough fluid in the circulation. Nerve problems can also cause O.H. It’s the nerves that tell the heart to beat faster and the vessels to squeeze a little tighter.When this patient came to the E.D., he was often given intravenous fluids to try to fill up a suspected empty tank. It never seemed to help. That made his doctors think that in his case the cause was neurogenic — his nerves weren’t delivering their essential messages. And for this patient, that seemed a reasonable explanation, because it was clear that at least some of his nerves weren’t working well. He had a severe peripheral neuropathy that left his feet mostly numb, though occasionally they burned and tingled as if they were asleep.Photo illustration by Ina JangChecking His Heart RateIt was early morning when Dr. Matt Slief, a resident at the end of his first year of training, saw his newest patient. The cheerful silver-haired man described the strange spells he had when he stood up that more than once had landed him on the floor in a dead faint. “It doesn’t last long,” he told the young doctor, “but it sure is embarrassing.” Slief quickly examined the patient and promised to return later that morning with the rest of the team. After he finished seeing his patients, he hurried to the team room where he was to meet with Dr. Robert Centor, the attending physician. Centor was a couple of years older than the patient but still hard at work — though he described himself as semiretired.After hearing about the patient with the positional changes in blood pressure, Centor asked the young doctor: “What was his heart rate?” Slief quickly checked. Every time the patient’s blood pressure went down, his heart rate went up, he reported. Centor nodded. “In that case, I doubt that his orthostatic blood pressure is caused by his nerves,” he said. If the nerves can’t tell the blood vessels to squeeze, they also won’t be able to tell the heart to beat faster — so in neurogenic O.H., the heart rate remains stable even when the blood pressure drops. And that’s not what happened with this patient.Clearly his problem wasn’t in his nerves. And it didn’t seem to be a problem with blood volume, because giving him fluids never helped. There were other, less common causes to be considered. Centor challenged his team: What else could this be? By the time they next met, Slief had come up with an alternate possibility, but he worried it would sound far-fetched.Years before, the patient had fallen in the bathtub, broken his ribs and punctured a lung. Blood filled his chest and collapsed the lung. He had to be rushed to the hospital. Patients who are stuck in bed while in the hospital are at risk of developing blood clots in the veins of their legs because they are immobilized. Clots form when blood isn’t moving. These patients are usually started on blood thinners to reduce that risk. Because this man had bled into his chest, blood thinners weren’t a good option for him. Clots that form because of immobility block veins and cause swelling and pain, but they can also be deadly if they travel through the body and end up in the lungs or brain. So his doctors had chosen to put a filter in the main vein that brought blood from his legs back to his heart — a vessel called the inferior vena cava — to catch any clots that formed and broke free.These filters are supposed to be removed a few months later when the risk of clotting goes down, but many are not removed on schedule. This one had been left in place for more than 15 years. What if, Slief suggested after explaining this history, the filter had done its job and captured clots and they were now blocking the entire vessel? Could that cause his positional hypotension? Centor listened thoughtfully. He’d been a doctor for 45 years and had never seen this. And yet it was an interesting idea. Certainly worth considering.One of the many advantages of the V.A. Hospital system is that it has computerized medical records going back decades. Slief did a deep dive into this man’s medical history and hit what looked like some promising results. Seven years earlier, the man had a CT scan that showed an almost total blockage of his vena cava. Was it possible that the extra blood that was supposed to go from the legs to the brain when the man stood up didn’t get there fast enough because of the narrowed vena cava?The Daddy-Longlegs DeviceThere was really no way to test this hypothesis, but it made sense. They explained to the patient that the next step was to get the filter out. The patient was eager to try. The team reached out to Dr. Bill Parkhurst at the University of Alabama at Birmingham Hospital, who specialized in this kind of procedure.The patient was sedated for the operation. Parkhurst put a tiny tube through an incision into the patient’s jugular vein in his neck and slowly advanced it down past the heart into the vena cava where the filter was located. These contraptions look like daddy longlegs with tiny hooks at each foot to hold them in place in the vein. Where the body of the insect would be located was a small hook. Parkhurst used a tiny gripping tool to grasp the hook and pull the filter up through the vena cava and out through the small incision in the patient’s neck. Next Parkhurst inserted tiny balloons that he inflated to reopen the threadlike stream through the narrowed vena cava. He then positioned a stent to hold the vessel open. He continued this process down the primary vein of each leg. The procedure took six hours and required nine stents, but finally there was good blood flow between the legs and the heart.The first time the patient stood up after this procedure, he was amazed. The dizziness was gone. It has been four months and it hasn’t come back. No weak legs, no lightheadedness, no falls. His feet are still numb, but he can live with that so long as they remain on the ground and he remains upright.Slief is modest about making this obscure diagnosis. There are only a handful of case reports in the medical literature. Still, Slief told me, it does make you wonder if maybe this is happening more often than reported. He’s certainly going to be looking for it.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 her at Lisa.Sandersmdnyt@gmail.com.

Could the disease be back?The doctor’s voice over the phone was warm and reassuring. The patient, a 62-year-old man, had a chest CT earlier that day, and Dr. David Smith, his longtime P.C.P., was telling him that the radiologist saw a mass. It sounded bad, but it probably wasn’t cancer, Smith told him. “I didn’t want you to see the report and worry,” he added. The report said that the mass in his lungs looked like a neoplasm — the fancy word for tumor. But it went on to acknowledge that it could also just be left over from the really bad pneumonia the man had three months earlier.And it had been a bad pneumonia. First he started coughing. Then he had trouble taking a deep breath. He burned with fever and had a stabbing pain in the upper right part of his back with every breath. He tried to tough it out with cough syrup and ibuprofen, but when it wasn’t getting better, his fiancée insisted that he call his doctor. The nurse who called him back sent him straight to Yale New Haven Hospital. A chest X-ray showed a large cloud of white and gray taking up most of the upper part of his right lung — pneumonia.He was given antibiotics to treat a presumed bacterial infection, and by the next day he started to feel a little better. He was sent home to finish the five-day course. The fever went away, and then the back pain, but the cough lingered. Just taking a breath or talking could trigger a long bout of hacking so violent it left him breathless.Chest X-rays repeated after one month and then two months looked better. The cloud shrank to a blob the size of a peanut. But when it was still there after three months, Smith ordered a chest CT. That was the report that Smith was calling his patient about. The patient listened quietly but was still worried. He already had cancer once, decades earlier, and the possibility that he could have it again scared him.Samples to the C.D.C.Smith knew his patient well and had already reached out to one of the lung-cancer experts at Yale New Haven Hospital to consult her on whether a biopsy was needed. She agreed with the radiologist: It was probably just left over from his pneumonia. Give it a couple of more months, she advised, and if the mass was still there, that’s when you’d do a biopsy.A few weeks later, the cough finally went away, and the man felt quite well. Still, the possibility of lung cancer haunted him. He had never smoked, but he was a woodworker, a sculptor, and often eschewed the mask, even when exposed to airborne particles. As an artist, he sometimes felt that the mask was a barrier between him and his work.When his doctor called after the second CT and told him that the mass in his chest had grown, the man felt a pang of real fear. The biopsy was uncomfortable but not painful. He lay on his back and a long needle was introduced between two ribs. Because of the medications he was given, he felt only an intense pressure. The results were a relief. It wasn’t cancer, they said. Instead, it looked like some kind of infection. A few of the samples showed strange-looking cellular organisms that no one seemed to be able to identify. The pathologist sent pictures of the tissue and the unrecognized organisms to the Centers for Disease Control and Prevention in search of a diagnosis.Days later they sent back their answer. This was, they believed, a fungus called blastomyces. Had the patient been in the Ohio or Mississippi River Valleys recently? Or anywhere in the Midwest or South? Blasto, as it’s called familiarly, lives in the dirt there and few other places. If inhaled, it can cause a serious infection in the lungs called blastomycosis, which could be fatal if not treated. Smith immediately referred the patient to the infectious-disease team. The doctor on service that week was Dr. Marwan Mikheal Azar, who, as luck had it, was an expert in fungal diseases.Azar had only recently finished his specialty training. He had done additional training in microbiology and examined the images that had been sent to the C.D.C. eagerly. After the first look, though, he wasn’t sure the C.D.C. had got it right. The fungi seen in the slides were too big to be blastomyces. Those were tiny organisms — less than one-tenth the diameter of a human hair. The organism shown in these pictures was big in comparison — maybe about the width of that human hair. Moreover, one of the cells had a recognizable pattern. It couldn’t be seen completely but looked like a sack filled with tiny beads.That image suggested a very different fungus, one known as coccidioides. Like blastomyces, cocci (as it’s called) lives in dirt. But it is endemic to a region on the other side of the country — especially the Western desert of Arizona, California and Mexico. If inhaled, the organisms could end up in the lungs and cause a pneumonia called, variously, coccidioidomycosis or desert rheumatism or Valley fever. Each of the tiny beads Azar saw inside the organism was actually a baby fungus. When the beads grew large enough, the sack would rupture, releasing the offspring. Each bead would grow and develop tiny seeds of its own.Photo illustration by Ina JangA Visit to a Dude RanchThe patient was a slender, energetic man who looked younger than his 62 years, Azar noted when he met the man the following week. Informed by the results of the biopsy, the infectious-disease doctor asked the patient the same questions the C.D.C. raised about his recent travel. Had he been to the Midwest or the South in the past year or so? Maybe around the Mississippi or Ohio River Valleys?He had, the patient replied, but not for decades. But, he added, he spent several days at a dude ranch in Arizona a few weeks before he got sick. The pneumonia had been awful, but he felt fine now. Azar felt a moment of satisfaction: He was in Arizona just before getting sick? This probably was coccidioidomycosis. And yet the C.D.C. thought it was blasto. Azar needed to be sure of what he was treating. Blastomycosis was a much more serious disease than coccidioidomycosis, requiring significantly longer treatment. He sent a sample of the tissue taken from the man’s lungs to the C.D.C. for genetic identification of the yeast. In the meantime, Azar started the man on an antifungal medication, itraconazole, that worked against both types of yeast.It took weeks for the results to come back. But finally they had a definitive answer: It was cocci.Relieved to be free of a possible cancer diagnosis, the patient jumped onto the internet to read up on Valley fever. It was all over Arizona. His sister-in-law reminded him later that there used to be a card about the disease in the rooms of the dude ranch they visited every year for the past 30-something years. He quickly found the Valley Fever Center for Excellence at the University of Arizona College of Medicine-Tucson, only a few miles from the dude ranch. It was set up to teach doctors and patients about the infection. Two-thirds of all patients with cocci got it right there in Arizona. These were the real experts in cocci, the patient told Azar. He should call them. Azar wasn’t sure what he could learn from these folks. But he did have some questions. So when the patient brought it up again, he called.He had read the guidelines on the treatment of this disease — written, as it turned out, by the physician who led the Center for Excellence — and their recommendation was to stop treatment if the patient didn’t have symptoms. Could that be right? “I learned so much,” Azar acknowledged to the patient. Most important: The man didn’t need the medication. His body had already neutralized the bug.It’s amazing, Azar told me, that something can be so ordinary in one part of the country and so rare every place else. If that patient had presented to the E.R. in Tucson, it’s more likely that they would have recognized what he had as Valley fever. If he had symptoms, they would have treated him; if he didn’t, they wouldn’t. But they certainly would not have ordered a biopsy. And they would have never thought for a moment that he had cancer.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 her at Lisa.Sandersmdnyt@gmail.com.

She was a young athlete who suffered frequent head injuries. Her family assumed that was the cause of her strange symptoms — then she had a seizure.“What just happened?” The 16-year-old girl’s voice was flat and tired. “I think you had a seizure,” her mother answered. Her daughter had asked to be taken to the pediatrician’s office because she hadn’t felt right for the past several weeks — not since she had what looked like a seizure at school. And now she’d had another. “You’re OK now,” the mother continued. “It’s good news because it means that maybe we finally figured out what’s going on.”To most people, that might have been a stretch — to call having a seizure good news. But for the past several years, the young woman had been plagued by headaches, episodes of dizziness and odd bouts of profound fatigue, and her mother embraced the possibility of a treatable disorder. The specialists she had taken her daughter to see attributed her collection of symptoms to the lingering effect of the many concussions she suffered playing sports. She had at least one concussion every year since she was in the fourth grade. Because of her frequent head injuries, her parents made her drop all her sports. Even when not on the playing field, the young woman continued to fall and hit her head. The headaches and other symptoms persisted long after each injury. She saw several specialists who agreed that she had what was called persistent post-concussive syndrome — symptoms caused either by a severe brain injury or, in her case, repeated mild injuries. She should get better with time and patience, the girl and her mother were told. And yet her head pounded and she retreated to her darkened room several times a week. She did everything her doctors suggested: She got plenty of sleep, rested when she was tired and tried to be patient. But she still got headaches, still got dizzy. She found it harder and harder to pay attention. For the past couple of years, it had even started to affect her grades. Early in September, the mother got a call from her daughter’s high school. Her daughter was ill and needed to go home. “What happened?” her mother asked her later. The girl answered: “I don’t know. I was in class; it had just started. The next thing I knew, class was almost over and everyone was standing around me.” That evening one of the girl’s friends sent the mother a text. I want to tell you what I saw, he said. They were in class, and he noticed that his friend’s hand started to shake. She seemed kind of zoned out, and she was drooling. It only lasted a minute or so, but it was strange, the boy said. Fearing her daughter may have had a seizure, the mother looked for a specialist. She found one in Stamford, a half-hour south of their home in suburban Connecticut. This doctor made an odd request: Keep your daughter awake the night before the appointment. She would need an EEG, and fatigue can lower the threshold to have a seizure and make the problem easier to find, he explained. But the test was normal. She may have had a seizure, the neurologist said, but these are often isolated events. A Very Strange Night But just a few weeks later, on that visit to the pediatrician, it happened again, and right in front of the doctor. After hearing that she might have had another seizure, the young woman had another question. “Can I still go to homecoming?” she asked.“Absolutely,” the doctor answered. The mother was a little surprised, but pleased. Maybe this really was good news. That evening, after the girl left to go to the homecoming dance, the doctor called. “That wasn’t a seizure your daughter had in my office,” he told her. “I think it was a panic attack.” After a seizure, he explained, patients usually have a period of severe fatigue and confusion. “No one who’s had a seizure asks about going to homecoming,” he said. She had been breathing heavily before her strange episode in his office. He thought she was hyperventilating — something that can occur before a panic attack — and gave her a paper bag to breathe into. She had barely put the bag to her lips when she started flailing her arms and legs. Panic attacks are common, especially in this age group. She should probably see a psychiatrist, he added. Hearing this, the mother was stunned. This doctor had been the family’s pediatrician since their son, now 23, was born. He had always been great — the kind of doctor who always goes the extra mile. But this time the mother was certain he was wrong. The young woman was home that night by 8:30. She spent barely 20 minutes at the dance. The music was too loud, she told her questioning parents. The flashing lights gave her a headache. She went straight to bed. Hours later her mother eased open the door to her daughter’s room, to check on the girl before going to bed herself. As she gazed at her daughter, the young woman began to shake. It wasn’t the wild flailing she saw in the doctor’s office. It was like the kind of shaking chills you might get from a fever, but more so. The episode lasted only a few seconds. The mother, far too worried to go to her own bed, lay down next to her daughter to wait for the strange shaking to recur. She was awakened a couple of hours later. The entire bed seemed to be moving. Her daughter’s eyes were closed, and her body was shaking. Again, it lasted only seconds. Was this a seizure? She jumped out of bed and called the pediatrician. The mother didn’t know the doctor who called her back, and she wasn’t reassured by the doctor’s reminder that her daughter had a similar episode that day that was thought to be a panic attack, not a seizure. Hanging up, the mother felt terribly alone. Who would know what she should do? Suddenly she remembered the neurologist who did the EEG. He’d said that it might have been an isolated episode. But clearly it wasn’t. Who has heard of a panic attack happening in the middle of the night?That neurologist wasn’t on call, she was told by the answering service, but someone would call her back. A few minutes later, her phone rang and a lightly accented voice identified the caller as Dr. Cigdem Akman. She was a pediatric neurologist from the NewYork-Presbyterian Morgan Stanley Children’s Hospital in Manhattan. The mother recounted the long day’s events. After describing what happened at the pediatrician’s office she paused, then added, “Her doctor thought it was a panic attack, but my daughter has never been one to lose her head.” Then she described the bed shaking she saw and felt that evening. “I have no doubt that your daughter is having seizures,” the doctor told the mother. There was nothing that needed to be done right then, but her daughter should be evaluated. Akman would arrange for her to be seen in the video EEG lab. A 48-hour study could reveal what was going on. Photo illustration by Ina JangOne Visible Abnormality Mother and daughter traveled to the hospital’s epilepsy-monitoring unit two days later. In the first 24 hours she was monitored, she had eight seizures, one while awake and seven when sleeping. During the seizure when she was awake, the young woman was able to walk and talk intelligibly. The only obvious abnormality was her eyes. She blinked rapidly several times, then her chin lifted slightly and her eyes rolled back. It lasted only seconds but the EEG showed the presence of a type of generalized seizure called an “absence seizure” — characterized by a lack of attention. The strange eye movements indicated a rare type of absence-seizure disorder called Jeavons syndrome. She was immediately started on a potent antiseizure medication. Jeavons was first described in 1977. It usually starts in childhood, though is frequently not diagnosed until adolescence. It is much more common in girls than boys. Affected children have seizures that are very brief, lasting only a few seconds, but often occur many times a day. Untreated, these seizures can impact learning. And they can change from absence seizures to tonic-clonic or grand mal seizures, as this young woman’s had. It took a few months for Akman to find the right medications for her, but since starting that medication, she has had no seizures at all. Once her seizures were under control, she stopped having accidents. The headaches disappeared. So did the fatigue and dizziness. For much of her life, the young woman was known to have episodes of inattention. These had been attributed to her many concussions. Now it was clear that many, if not most, of them were actually seizures. On the antiseizure medication, the young woman’s grades went up. She is now a junior in college, majoring in neuroscience.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 her at Lisa.Sandersmdnyt@gmail.com.