Diagnosing PPMS; not an easy task!

PubmedKelly et al. A proposed modification to the McDonald 2010 criteria for the diagnosis of primary progressive multiple sclerosis. Mult Scler. 2012 Nov.

BACKGROUND: The diagnostic criteria for primary-progressive multiple sclerosis (PPMS) have undergone revision over the last 20 years. Cerebrospinal fluid oligoclonal bands (CSFOBs) have received less emphasis in recent revisions of the McDonald criteria. The aim of this study was to examine the sensitivity of the diagnostic criteria for PPMS with particular reference to spinal cord criteria and examine the utility of CSFOBs in a cohort of PPMSers.

METHODS: All new PPMS diagnoses between 1990 and 2011 were identified. Baseline clinical details and paraclinical evaluations including MRI of the brain, spinal cord, CSF and visually evoked responses (VERs) were assessed. The proportion of MSers who met the requirements for diagnosis of PPMS on the basis of Thompson's and the McDonald Criteria (2001, 2005, 2010) were determined.

RESULTS: There were 88/95 PPMSers who had at least two diagnostic investigations. The sensitivity of Thompson's and the McDonald 2001 criteria was 64%; the McDonald 2010 revisions gave the highest sensitivity (77%); the McDonald 2005 criteria had intermediate sensitivity (74%). The combination of CSFOBs and MRI of the brain yielded the greatest number of MSers demonstrating dissemination in space (DIS) on only two investigations. VERs did not aid diagnosis. Reducing requirements for the number of spinal cord lesions (symptomatic or not) to one increased diagnostic sensitivity to 84%.
CONCLUSION: An alternative criterion requiring two of: i) MRI of the brain with one or more lesions in two of three regions typical for demyelination; ii) the presence of one T2-weighted spinal cord plaque (typical for demyelination); iii) CSFOBs; would increase the diagnostic sensitivity for PPMS

"The problem with this paper is that the author's have not really considered what a diagnosis of MS means? The truth is that the "gold standard", i.e. the 2001 criteria have never been validated. Therefore I prefer to use the the term accuracy. True validation requires a post-mortem follow-up to check that the ante-mortem diagnosis (in-life) is confirmed in death. Another issue is the positive and negative predictive value of the criteria, with PPMS this is critical; i.e. if you fulfil the contemporary criteria what is the likelihood that you have PPMS or more importantly the likelihood you do not have PPMS? The negative and positive predictive values vary depending on how common PPMS is in the part of the world the criteria are being tested or applied." 

"This rant may be confusing; I promise to post a piece on it to simplify the message in the near future."

"I never make a diagnosis of PPMS without spinal fluid analysis; it is vital to exclude MS mimics and to make sure that there is evidence of immune activation within the CNS or spinal cord. More recently it has been shown  that PPMSers with a negative spinal fluid analysis do better than PPMSers with a positive CSF analysis.Why? I think this suggests  that they may be two different diseases. As a result of this observation the two PPMS trials that are currently running (fingolimod and ocrelizumab) both require trial subjects to have abnormal CSF findings. So despite the current diagnostic criteria not requiring an abnormal CSF the steering committees who designed these trials have rejected the 2010 and 2005 criteria and have applied the 2001 criteria. Good on them!"

"I am sure a lot of you will have questions and comments on this post. For example, my neurologist has diagnosed me with PPMS without doing a lumbar puncture? Is that okay?"

Labels: ,