The ultimate price of a false diagnosis

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.


Kleinschmidt-DeMasters and Tyler. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med. 2005 Jul 28;353(4):369-74.


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.


Berger and Deisenhammer. Progressive multifocal leukoencephalopathy, natalizumab, and multiple sclerosis. N Engl J Med. 2005 Oct 20;353(16):1744-6; author reply 1744-6.


“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’.”

4 thoughts on “The ultimate price of a false diagnosis”

  1. Hello, I don't understand what the difference is between a lesion and a plaque, and what makes an MS lesion different to other lesions which may show up on an MRI of the spinal cord and brain? Would be grateful for an explanation! Thanks!

  2. Re: "… are you a scientist or an artist?"This refers to my clinical hat! I wish the practice of neurology was a science.

  3. Re: "I don't understand what the difference is between a lesion and a plaque, and what makes an MS lesion different to other lesions which may show up on an MRI of the spinal cord and brain?"A lesion is a non-specific term that must be interpreted in context. On MRI a lesion could be referring to a MS lesion or a lesion caused by a stroke. There are many different diseases that cause lesion on MRI that can look like MS lesions. This is why we have to be careful when making a diagnosis of MS. In comparison a plaque is a term that we use when we are referring to a MS lesion at post-mortem; plaques are the demyelinated lesions that can be seen with the naked eye in the brain and spinal cord.

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