Marieke van Rosmalen

Chapter 6 104 DISCUSSION With this study, we show that quantitative MRI techniques reveal differences in the brachial plexus between patients with CIDP, MMN, MND and healthy controls. CIDP is characterized by lower FA and higher RD than MMN, MND and healthy controls, whilst MMN is characterized by higher FA values than CIDP and MND. Patients with MMN and healthy controls did not differ. These differences between CIDP and MMN are the most remarkable and important finding as they emphasize important differences in the underlying pathophysiologies. This is the first comparative quantitative MRI study in a relatively large cohort of patients with CIDP and MMN. Diffusion parameters obtained from the sciatic, tibial, median, ulnar and radial nerves were previously reported in smaller cohorts. 14–17,19 The absolute differences of the measured parameters are around 2% between study groups, which indicates that differences are probably only found in larger groups. However, the finding of a decreased FA and an increased RD in our study patients with CIDP is in agreement with previous findings, indicating that this DTI profile is characteristic for CIDP and can be found throughout the peripheral nervous system. 14–17,19 Experimental animal studies showed that increased RD may correspond with loss of myelin integrity. 10–12 The combination of decreased FA and increased RD has also been reported in patients with Guillain-Barré syndrome (GBS) and demyelinating types of Charcot-Marie-Tooth (CMT), which corroborates that this reflects the disturbance of myelin integrity in peripheral nerves caused by inflammation. 32–35 The longer T2 relaxation times and lower fat fraction in the CIDP cohort compared to the MND cohort indicate the presence of free water, which may also be due to inflammation, and have also been reported at the lumbosacral plexus. 21,22,36 Although decreased FA in combination with increased RD is a robust finding in patients with CIDP, absolute diffusion values differ between proximal and distal nerve sites. 14–17,19 This is probably explained by the proximal to distal decrease in the diameter of fascicles with a corresponding increase in the density of the perifascicular connective tissue. 37 In the well-organized tissues of the distal peripheral nerves, water molecule movement is more restricted in specific directions, which results in larger isotropic diffusion and a higher FA. The FA values of the brachial plexus in our study were lower than in previous studies of distal peripheral nerves in arms and legs, which is in line with this hypothesis. 14–17,19 FA and MD are summary measures from eigenvalues. Changes in FA and MD are therefore driven by changes in AD or RD. In CIDP, the increase in RD seems to drive the changes in FA and MD. RD indicates less hindrance of diffusion for water perpendicular to the nervous tissue. This can be the result of various cellular mechanisms, such as demyelination or a disturbance of the cytoskeleton caused by a loss of neurofilaments and microtubules. We think that our findings may reflect demyelination rather than a disturbance of the cytoskeleton as histological studies reported myelin detachment and myelin loss without damage to axons induced by macrophages around the