In one of the original natalizumab studies a 46-year-old woman unfortunately died from progressive multifocal leukoencephalopathy (PML) after having received 37 doses of natalizumab. Although PML was confirmed at post-mortem there was no pathological evidence that this person had MS.
According to the established definition of MS used at the time the patient should probably not have been diagnosed as having MS. The following letter to the journal high-lighted this issue very well.
"In all likelihood this patient probably did not have MS. The great tragedy is that she died of a complication of receiving natalizumab."
"The lesson here is not to rush into making a diagnosis of MS; if there is uncertainty it is better to wait for the disease to fully declare itself. To quote one of my great clinical mentors Professor Tom Bothwell: 'Time is often the best diagnostician'."