If you are dealing with a neurologist who knows well how to use the 14-3-3 test then, the likelihood of an incorrect diagnosis is small. The 14-3-3 is best applied when the PRETEST probability of having CJD is HIGH..in other words, just on clinical history and physical examination the neurologist believes that CJD is high on the list of possibilities. Assuming the clinical diagnosis is highly likely to be CJD, the neurologist will likely pursue other testing measures such as an EEG and MRI of the brain with FLAIR and DWI sequences (more sensitive and specific in most patients than the 14-3-3 assay). The neurologist will also work very hard to rule out all possibilities of any other type of infectious or demyelinating illnesses (including inborn errors of iron/copper/zinc metabolism) as well as reversible or treatable forms of dementia in categories such thyroid encephalopathy and B12 deficiency. Under these circumstances then, the clinician will have done everything possible to find every other diagnosis. Therefore, if this type of comprehensive investigation does not yield any positive results then, what you are left with is the original presumptive differential which should be then, diagnosis of the most likely clinical diagnosis. This could be verified upon autopsy but in my experience it is rarely if ever the case that families will ask for that kind of confirmation if the workup as I ve described has been carried out. In other words, the diagnosis is as certain as it can be under these conditions. If, however, this type of workup has NOT been pursued then, there is still more to do in my opinion to solidify the final thoughts and judgments of what your husband may or may not have. Just as an aside- I understand the implications and use of the 14-3-3 CSF assay in quite a bit of detail since it was originally developed and tested at my training institution during the time I was a neurology resident. The doctor who headed up the initial discovery of the protein and its subsequent approval for CJD screening by the FDA was Head of the Neuropathology Division at that time. Trust me when I tell you that we were intensely trained on when and how to use this test as well as its interpretation as well as when NOT to use it and when NOT to put very much stock into the results. Feel free to send more questions to: www.bit.ly/drdariushsaghafi and I would also appreciate your 5 STAR rating of our interaction.