Marieke van Rosmalen

Chapter 8 144 healthy controls (n = 10 – 18). 30,66–73 As large and systematic studies are currently lacking, we performed a relatively large cross-sectional study in chapter 6 and evaluated quantitative MRI techniques (i.e. DTI, T2 mapping and fat fraction analysis) in patients with CIDP, MMN, MND and healthy controls. We found that CIDP is characterized by a lower FA and a higher RD than MMN, MND and healthy controls. Fat fraction was decreased and T2 relaxation times were increased in patients with CIDP. In the light of the earlier assumptions on diffusion parameters and histology, we think that the increase of RD and the decrease of fat fraction most likely reflects demyelination in our patients with CIDP. Myelin detachment and myelin loss induced by macrophages around the (inter)nodal regions have been reported in several studies on biopsies in CIDP. 74–80 We explain the increased T2 relaxation as a result of oedema surrounding the nerves, caused by an inflammatory reaction. RD values differed between patients with MMN and patients with CIDP, but not between patients with MMN, MND and healthy controls. This is one of our most remarkable findings as it emphasizes important differences in the underlying pathophysiologies of CIDP and MMN. We think that demyelination is probably not the dominant pathophysiological process in MMN and this is supported by scarce histological reports and electrophysiological studies that report a changed axon structure but largely intact myelin sheets. 81–84 Also, observational studies have noted that most patients with MMN suffer from cold paresis, a feature that is not compatible with demyelination. 85 The similarities in abnormalities across diagnostic NCS, nerve ultrasound and qualitative MRI in clinical practice are therefore remarkable as well. These similar abnormalities are more likely to present common endpoints of different pathophysiological mechanisms rather than comparable etiologies, although this should be established in comparative studies that evaluate both histology and DTI. Future studies on quantitative MRI and histology The major limitation in the interpretation of the results of quantitative MRI studies is a lack of knowledge of the exact correlation between quantitative MRI parameters and histological changes. There are no human studies available, mostly due to the obvious ethical concerns. The ultimate, albeit theoretical, study should, in my opinion, include nerve biopsies in patients with CIDP, MMN and healthy controls, for example of nerve sites that showed conduction blocks on NCS, combined with MRI DTI, T2 mapping and fat fraction analysis of these sites. Nerve biopsy is an invasive procedure and could result in persistent nerve damage and loss of nerve function and is therefore not feasible. An alternative could be a post-mortem study in patients with CIDP or MMN but inclusion rate would probably be low and results could reflect mostly end stage disease. Abetter alternative is therefore the use of animal models such as experimental autoimmune neuritis (EAN) or equivalents, which is used to model Guillain-Barré syndrome and CIDP and can be induced in rats, mice, rabbits and guinea pigs. 86 Animals start to develop ataxia and weakness 2 weeks after immunization with peripheral nerve myelin proteins or other constituents. Quantitative MRI and NCS should be performed under anesthesia at baseline, after 1 week, 2 weeks and after full development of symptoms and its