When “Mad Cow Disease in Humans” is Misdiagnosed

Mad cow disease is also known as bovine spongiform encephalopathy (BSE). This is because the word “bovine” refers to cows (and other related animals) and the last two words refer to this being a disease of the brain and spinal cord (encephalopathy) that causes it to have a spongy appearance (spongiform). 

Mad cow disease is a deadly condition caused by an abnormal protein known as a prion, which enters the body when cows are fed the remains of other cows or infected sheep. The prions that cause mad cow disease are highly resistant to heat and are very difficult to kill. 

When humans eat cow meat infected with mad cow disease, the prions can enter the body and cause a similar disease in humans. When this happens it is known as variant Creutzfeldt–Jakob  disease (vCJD). The condition presents as a rapidly progressing dementia with hallucinations. Dementia is a progressive loss of cognitive and intellectual functioning without loss of consciousness. A hallucination is a strong sensory perception that one has of an object or event while awake, when no such object or event exists.

There are two other kinds of CJD. One is called familial CJD (fCJD), in which the patient inherits a genetic mutation (abnormality) that leads to the formation of prions that cause the condition. Lastly, there is sporadic CJD (sCJD), in which people develop the condition without any known risk factors. In other words, there is no evidence that they consumed contaminated meat and the condition does not appear inherited. The sporadic form is the most common form of CJD. This has sometimes been referred to as “mad cow disease in humans” (hence the title of this blog post) even though the two are believed to be unrelated.

Sporadic CJD can be very difficult to diagnose because it is such a rare condition. However, a rapidly progressing dementia is the first tell-tale clue. Diagnosis can be made by integrating the clinical history with the results of diagnostic studies such finding the abnormal 14-3-3 protein in a sample of CSF (cerebrospinal fluid, a cushiony fluid that protects the brain and spine and helps distribute nutrients to these structures), finding characteristic spikes on an EEG (electroencephalography, a test that measures electric brain waves), and finding bilateral abnormalities in the basal ganglia on a brain magnetic resonance imaging (MRI). MRI scans produce extremely detailed pictures of the inside of the body by using very powerful magnets and computer technology. The basal ganglia is an area of gray tissue deep inside the brain that controls movement.

In the current issue of JAMA Neurology, researchers from the University of California San Francisco reported the results of a study designed to examine how often patients with sCJD were misdiagnosed, who misdiagnosed them, what conditions they were misdiagnosed with, and when the correct diagnosis was made. The study involved 97 patients eventually proven to have sCJD based on a microscopic analysis of brain tissue.

The results of the study showed that only 18% of patients with sCJD were correctly diagnosed on the first evaluation and when this happened the diagnosis was almost always made by a neurologist.  However, the doctors  who most often made the wrong diagnosis were also neurologists as well as primary care physicians.  The average time from disease onset to correct diagnosis was 7.9 months, which was about two thirds of the way through their fatal disease course.

The study found that the top five misdiagnoses for sCJD were viral encephalitis (inflammation of the brain caused by a virus), paraneoplastic disorder (a disorder that mimics cancer but is not actually cancer), depression, peripheral vertigo (spinning sensation while sitting still), and Alzheimer’s disease (the most common form of dementia).

Suggested reading: The Pathological Protein: Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases
 
Reference:  Paterson et al (2013, in press). Differential Diagnosis of Jakob-Creutzfeldt Disease. JAMA Neurology.