“Certain dogmas about PPMS have crept into the field and have become entrenched as facts that need challenging; in particular that (1) PPMS in non-inflammatory, (2) PPMSers don’t have relapses and (3) PPMS is a different disease to relapse-onset MS.”
“The following pathology study done at Queen Square when I was doing my PhD clearly showed that PPMS is inflammatory, albeit at a slightly lower level than SPMS. The dogma has crept in because PPMSers have fewer focal lesions on MRI. This however does not mean that there is no inflammation; focal inflammation is simply occurring at a sub-MRI level. What MRI sees in relation to focal lesions is simply the tip of the iceberg. The PPMS iceberg simply looks different with less above the surface.”
Background: The dynamics of primary progressive multiple sclerosis differ from those of the more common secondary progressive form. The observation by MRI that the frequency of enhancement with gadolinium-DTPA, a marker for blood-brain barrier dysfunction, is significantly less in the primary progressive form, has led to the hypothesis that inflammation is less intense in this group.
|Slaying the dogma beast: which head should we cut-off?|
“In almost all PPMS trials done to date a proportion, albeit a small proportion, of PPMSers go onto have relapses. For example in the Rituximab trial in PPMS (Olympus Trial), 11 out of 439 (2.5%) of study subjects had a relapse during the 96 weeks of the trial.”
Hawker et al. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol. 2009 Oct;66(4):460-71.
“Similarly, about 5% of study subjects in the glatiramer acetate PPMS, or PROMISE, trial had relapses. Unfortunately, the exact number of relapses is not reported in the main manuscript. What is reported is MRI activity; 14% of 938 study subjects had Gd-enhancing lesions on MRI during the study. The latter is the MRI equivalent of relapses. Can we say that PPMS is non-relapsing?”
Note: “Please note that I have started refer to Gd-enhancing lesions as sub-clinical relapses in the hope that NICE will begin to accept MRI activity as a surrogate for clinical relapses. “
Wolinsky et al. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol. 2007 Jan;61(1):14-24.
Dogma 3: PPMS is a different disease to SPMS – WRONG!