Why etiology matters

Could you have solved this medical mystery? The author used what she learned from a shrewd CME lecturer to help an ailing friend.

By Hilary A. Tindle, MD
Internist/Vancouver, WA

Headaches," said neurologist Martin Samuels, his eyes intense, his forehead creased, "are normal."

My husband, Matt, and I were seated in the front row of a packed convention hall with about 200 other physicians, thoroughly engaged. We were there to hear Samuels, a professor of neurology at Harvard Medical School, deliver his annual "Neurology for the Non-neurologist" lecture at the American College of Physicians-American Society of Internal Medicine conference last year.

His brand of CME was as entertaining as it was useful, and usually everyone came away riding high after two hours of good medical cheer. This year, after a talk on headaches and movement disorders, I came away with something more.

Dr. Samuels polled the audience to see who had never had a headache. A lone attendee raised his hand.

"See? Headaches are normal!" said Dr. Samuels. "And everybody knows that everybody has headaches. So if it's normal, and everybody knows it's normal, why do people visit a doctor so frequently for headaches?"

Laughter rippled along the rows of seats and a whisper propagated through the crowd as several people answered in unison, "Brain tumor."

"That's right!" said Samuels. "They're worried about a brain tumor. They're afraid the headache represents a serious underlying disease.

"So, my lesson for today is this: No patient will ever be cured of headache until you look the patient straight in the eye and say, 'By the way, this is not due to a brain tumor.' The patient won't get better until you say these words. You must say them, and with a high degree of certainty."

Everyone laughed.

I recalled the scores of patients I had sent home without any such blessing. After all, it was common practice to deal with many conditions empirically—that is, merely manage the symptoms.

But perhaps I had become a bit too cavalier. More than once I had caught myself listening to the tired little voice inside that urges, "Just treat the patient! Does it really matter if you know the exact etiology of the condition?" But in Samuels' book, securing a firm diagnosis for each and every ailment was a necessary component of the healing process, not just a pie-in-the-sky medical school standard.

His humorous cajoling didn't dilute the essential truth he spoke: Patients need to know that they're not dying. In order for that to happen, Samuels was telling us, the physician must offer a diagnosis. Or at least definitively rule out the worst-case scenario.

Mysterious pain fells a budding surgeon

Ironically, the night before Dr. Samuels' lecture, I had heard about a case that perfectly illustrated his point. It involved the younger brother of my best friend from medical school. David and Lora, as I'll call them, had been raised in a small Jewish community in Cape Town, and had emigrated to America. They remained very close, and David visited his sister whenever he was, as he put it, "on holiday." Not surprisingly, he and I had grown close as well.

David's carefree demeanor and good looks seemed best suited to a life in front of the camera; anyone who knew him had to ask why he hadn't gone into modeling instead of medicine. Now he was a 27-year-old surgery resident.

Matt and I were staying at Lora's place during the ACP-ASIM conference, and the three of us were in her living room catching up when she broke the news about her brother. "You wouldn't recognize him," she confided with tears in her eyes. "He has such bad leg pains that he's on narcotics. The meds make him nauseated and he's lost 30 pounds."

"Pain from what?" I asked, struggling to picture David 30 pounds lighter. The kid brother who had been a poster boy for good health apparently now looked like a skeleton.

"Painful fasciculations. He can't stand in the OR for more than an hour. It's been like this for months. Now he's been asked to take an indefinite leave of absence."

I went through my differential diagnosis for bilateral calf pain, but most of the common stuff had already been ruled out. Cautiously, I broached the topic of wasting syndromes. Lora assured me that he had been tested and was HIV negative.

Then she added an intriguing fact: She and David had a distant cousin who began experiencing severe leg cramps when he was in his mid-20s. The cousin had never received a formal diagnosis, but was now in his 50s and was symptom-free on a daily, long-acting magnesium preparation.

A short while later, Matt remembered a patient he had treated during residency. The man had presented with a peripheral neuropathy that turned out to be a paraneoplastic syndrome. By definition, such a syndrome is triggered by a tumor. In this particular case, the man's peripheral neuropathy was associated with underlying B-cell lymphoma.

There was an uncomfortable silence in the room. None of us wanted to go there.

"What about depression?" I offered. Lora acknowledged that David's usual good cheer was gone, but she was certain that her brother's mental state was secondary to his inability to do any of the things he wanted to do—operating, socializing, sleeping, in short, existing—without pain.

David had seen an internist, a rheumatologist, a gastroenterologist, and a neurologist. The neurologist had gone so far as to obtain a muscle biopsy, but it revealed nothing. Idiopathic leg pain, the doctors finally concluded. Six months into his progressive illness, David had no diagnosis, and he was shutting down emotionally. After several hours of racking our brains, we had gone to bed disillusioned.

Can the expert provide the answer?

When my thoughts returned to the lecture, Dr. Samuels had launched into a systematic review of movement disorders. "When all of the muscle fibers attached to one single anterior horn cell fire synchronously, what is this called?"

"Fasciculations," answered several people.

My pulse quickened. Matt and I exchanged glances as we asked ourselves the same question: Could this man help us with David's diagnosis?

"If your fasciculations bother you," he continued, "you can take magnesium, by drinking milk. Or you can take quinine, a sodium channel blocker, in the form of tonic water, like Schweppes. If that doesn't work, just add some gin to it."

Applauding that final wisecrack, the audience filed out. Matt and I fought our way against traffic to join the small crowd that had gathered like a garland around Samuels. He listened intently while we presented David's case—the progressive nature, the weight loss, the leg pain, the negative muscle biopsy. Samuels rubbed his chin with one hand and squinted. I offered the piece of family history involving the cousin, and he mulled this over for about 15 seconds.

"By themselves, fasciculations are normal, but with the pain and family history, this sounds like Isaacs' syndrome." As I learned later, Isaacs' syndrome is a condition in which the body produces antibodies against its own voltage-gated potassium channels.

"There is a familial form and a paraneoplastic form, so it's very important that he has this looked into," said Samuels. He gave the name of a reference, suggested that David see a movement-disorder specialist, smiled, and went on to the next question. I knew I had just been given a gift, and I had to stop myself from throwing my arms around Samuels and any innocent bystanders.

"And by the way," he said, turning back toward me, "The usual treatment is Tegretol."

A proposed diagnosis raises troubling questions

That evening I began a MEDLINE search while Lora called relatives to get more family history. My husband related everything we had learned to David, who had dropped by his sister's place for a visit. He was visibly worried. No one—let alone a 27-year-old—wants to be diagnosed with a paraneoplastic syndrome. It didn't help that his father had died young from lymphoma.

If this was in fact Isaacs' syndrome, there was about a 50 percent chance of it being the less fearsome, familial version, which meant there was a 50 percent chance that it was not. David would need, among other things, a chest-abdomen-pelvis CT scan to look for any underlying malignancy.

He tried to sound encouraged, but we could see by his expression that the information had only frightened him more. It seemed to take all his resolve just to agree to follow up on the lead. I wanted to be able to tell David that his fasciculations were not due to a serious underlying condition. But I couldn't say that with certainty.

I spoke to Lora a number of times in the ensuing weeks, but was reluctant to ask about David. Then, about six months later, the phone rang. It was David. His voice was strong and jubilant. He had taken Samuels' advice and had seen a movement-disorder specialist. He was pain-free on Tegretol. To everyone's surprise and relief, he had the familial form of the disease. No tumor.

"You have no idea what you've done for me!" He had clearly regained his joy. "I'm back at work full time. While I was sick, I had forgotten what I love about surgery. Now I remember why I went into this field."

David was not dying. At least not today, and not from this particular ailment. But it wasn't until my friend became dangerously ill that I saw how the nameless face of disease—and the generic treatment that often accompanies it—can threaten to ruin a person's life. Does it really matter that you know the exact etiology of a patient's condition? Absolutely.

And if you don't know the answer, find someone—like Martin Samuels—who does.

 

Hilary Tindle. Why etiology matters. Medical Economics 2002;7:130.