Wednesday, March 26, 2014

How To Act When We Don't Know Something!

After three years of grueling, hands-on training in Internal Medicine at one of our nation’s greatest hospitals, I’d like to think I’ve seen it all.  But the truth of the matter is that I have just skimmed the surface of the ocean of disease that is out there.  I sometimes found that even my senior attendings, after decades of having cared for patients, would get stumped at times.  This got me thinking.  What guides us in treating patients whose diagnoses remain a mystery or are not the “bread and butter” cases that we are taught in medical school or residency?

In November of 2010, I was called to the Emergency Department to evaluate a woman who had been sent in by her rehabilitation facility because she was not acting herself.  Ms. Jackson (as I will refer to her here in order to keep her identity confidential) was a 51 year-old woman who had recently been diagnosed with the Human Immunodeficiency Virus (HIV) infection.  She had been sent to the rehabilitation facility after presenting to a local hospital with weakness and was found to be anemic.  Further testing revealed that she had some inflammation of her stomach lining, so this was treated and she seemed to be improving.  But in the ensuing days, her ability to perform higher-level cognitive skills began to decline over the span of two weeks.  Her daughter noticed it first, and then medical personnel began to pick up on overt signs of “encephalopathy” – a generalized disturbance of brain function.  So they brought her to the hospital, and this is where I met her for the first time.  

Ms. Jackson was not the typical case of encephalopathy that came through our emergency room doors.  Most of the time, in the barrage of blood tests and imaging that most patients with this symptomatology are subjected to by the first physician who treats them, a hint is usually uncovered which oftentimes leads to the answer.  And then I start appropriate treatment as they continue being cared for on the medical ward, and the patient sometimes gets better.  Things were different for Ms. Jackson.  Her blood tests and imaging were of no help.  I even drew fluid from around her brain and spine – the infamous “spinal tap”.  Even this was not helpful.

So I reset my thoughts and started over with her.  There were a few aspects to her physical exam that were a bit unusual.  For one, she was extremely cachectic.  This pointed to the chronicity of her disease, and was most likely due to the HIV infection itself.  She was also “catatonic” – her facial expressions were largely frozen in place, and it seemed as if she wanted to speak but did not have the energy to even move her mouth.  The most curious part of her exam was her apparent loss of the usual spinal reflexes in her arms and legs.  We asked specialists in neurology to assist in the diagnosis, and their recommendation was to send her blood to be tested for the presence of certain antibodies that can attack nerve cells – specifically, one that is named GQ1b.  The problem with the test for this antibody is that the answer is unavailable for up to two weeks.  In the meantime, we tried every antibiotic and steroid available to us to treat Ms. Jackson, hoping that one of them would spark her recovery.  But her illness prevailed, and eventually she began to have seizures and difficulty breathing.  After many lengthy discussions with the family, we decided it would be best to pursue comfort-care for Ms. Jackson so that she would no longer suffer.  After two weeks of merciless testing, imaging, and experimenting, Ms. Jackson left our ward to die at home in peace.

The next day, her GQ1b antibody test resulted – much to our surprise, she was found to have a small amount of this rare antibody circulating in her blood!  Now what?  Over the last week of her hospitalization, her family had begun the coping process that had ultimately culminated in them accepting her imminent death.  Was it ethical for me to call her family and tell them to bring her back to the hospital?  What does the presence of this antibody even mean?

I went to the medical literature for guidance.  It turns out that the GQ1b antibody is not very well understood.  What we know is that the nerve cells in our brain and spinal cord are made up of a substance called “ganglioside” that can sometimes be the victim of an antibody that our own body can spontaneously produce as a result of an intestinal infection or other abnormality of the bone marrow.  It is rarely observed, and because of this, much of what we know about the diseases caused by this antibody is from individual case reports.  This antibody has been connected to the Miller-Fisher syndrome and Bickerstaff brainstem encephalitis, both of which are very rare conditions – both of which shared features that were present in Ms. Jackson.  Albeit the quantity of antibodies present in Ms. Jackson’s blood were less than the usual patient with these potential syndromes, the laboratory result in front of us brought up the question of the next step.  In a patient still currently hospitalized, there would be a discussion of whether trying a procedure called “plasma exchange” would be beneficial.  It would involve plugging a very large tube into one of the patient’s large central veins, removing blood from the patient’s body, filtering it through a dialysis-like machine, and then returning the cleaned blood to the patient, free of any harmful antibodies.  But laboratories sometimes make errors, and what if the low level of antibody to GQ1b present in Ms. Jackson’s blood was a mistake and didn’t mean anything at all?

With Ms. Jackson, there remained the bigger question of whether interrupting a coping family’s mourning of a soon-to-be-departed family member was justified in the midst of a potential neurologic diagnosis whose outcomes after treatment are not predictable or guaranteed by any means.  And what about a single laboratory test whose significance is not fully understood and, frankly, may not mean anything at all?  As a comparison, some patients have detectable levels of rheumatoid arthritis antibodies circulating in their blood without ever developing symptoms of arthritis.  For these uncertainties, we decided not to interfere with the dying process.  This was not a blocked coronary artery that would lead to certain death if left untreated.  With Ms. Jackson, there were too many “ifs”.  So she passed peacefully with family at her side, and we were left to wonder whether pursuing aggressive therapies in this dying young woman would have changed anything.

With regards to our current practice of medicine, what we do now is based simply on what we know.  And what we know is heavily dependent on our past experiences of human disease.  Yet we know that there is a plethora of knowledge to be discovered, and hundreds of diseases still to be named.  So why should anything ever be deemed impossible?  One hundred years ago, we thought that heart attacks could only be treated with bedrest – now we have stents and surgery that have allowed people to take back their lives.  Thirty years ago, we believed all stomach ulcers were caused by stress – now we know a large portion of them are caused by bacteria that can be successfully treated with antibiotics.  In fifty years, I may look back at Ms. Jackson’s case and see a clear diagnostic or therapeutic option that we had never tried.  But such are the shortcomings and beauties of medicine.  Practicing medicine in the 21st century where our imaging and laboratory testing have sometimes accelerated past our knowledge of new human disease, it has never been more important to uphold the ethical principle of non-maleficence (i.e. “First do no harm”) to help guide us in making these tough decisions for our patients and their families.

Doc Veritas

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