Over-reliance on negative test results

In some cases, the correct diagnosis can be made based solely on information obtained from the history and physical examination. In other cases, we have a strong clinical suspicion regarding the diagnosis, which is then confirmed with specific ancillary testing. But, not uncommonly, the process is less direct and includes the formulation of a list of diagnostic possibilities, some of which are then eliminated based on additional studies. This activity is often referred to as “ruling out” this or that condition and common medical jargon reflects this process, so that the differential diagnosis is sometimes formulated as a list of “rule outs”. As we embark on this process, it is important to have a critical awareness of the limitations of the tests that we use. When a test comes back with negative results, did we in fact “rule out” that disease?

Falsely negative test results may occur for several reasons. In rare instances, a mishap in laboratory handling, such as mixing up the specimens from two patients, produces an incorrect test result. In other cases, falsely negative results are related to technical problems in performing the test. An example of this is an obese patient with headaches and papilledema whose CSF pressure is spuriously low via lumbar puncture performed under fluoroscopy.

In some cases, false negative test results are related to the inherent limitations of the particular test. As revolutionary as MR scanning has been to the practice of neurology, there are certain dis-

eases that just do not produce visible changes on neuro-imaging, and we look at a few such examples in this chapter. In other instances, a test may be quite sensitive when the disease process is generalized but is far less so when clinical manifestations are localized. This is often true for serum markers. For example, antineutrophilic cytoplasmic antibodies (ANCA) are positive in 97% of patients with systemic Wegener’s granulomatosis but in only 40% of those with “limited” disease, e.g. isolated sino-orbital manifestations. Similarly, the angiotensin converting enzyme (ACE) level is less likely to be elevated in cases of sarcoidosis confined to the optic nerve than in cases with pulmonary involvement. In the case of giant cell arteritis, the multi-focal nature of the disease process leads to occasionally false-negative temporal artery biopsies.

The common thread in these cases is a discrepancy between the clinical findings and the results of ancillary testing. Increasing reliance on test results is a striking trend of modern medical practice. There is no question that it takes less time to order a test and read the results than it does to piece out the diagnosis from a detailed history and physical examination. But when the test results do not match the clinical diagnosis, it is important to have the confidence to set aside the report and pursue the diagnosis, and sometimes initiate treatment, based on one’s clinical judgement. To this end, it is crucial to have a solid grounding in the clinical