Assessment of Citrullinated Myelin by 1H-MR Spectroscopy in Early-Onset Multiple Sclerosis

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Fig 1.
Patient 12. A, Short-echo single-voxel ¹H-MR spectroscopy (PRESS; TR, 1500 ms; TE, 30 ms; voxel size, 15 × 15 × 15 mm³) obtained from a right frontal CDL. B, Spectral narrowing with a resultant augmentation between 2.75 and 3.5 ppm shows the citrulline peak (arrow) between Cho and Cr peaks. C and D, No citrulline peak is present in the left frontal NAWM (C) and in the right temporal EDL (D).
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Fig 2.
A and B, Patient 4. A small citrulline peak (arrow) is shown between Cho and Cr peaks (A) in a voxel obtained from the left frontal NAWM, whereas it is absent in the voxel from the right frontal lesion (B) on short-echo ¹H-MR spectroscopy. C, Patient 1. The voxel from the left NAWM again shows a citrulline peak (arrow).

Table 1:

Presence and distribution of the citrulline peak in patients with MS according to the VOI site revealed by ¹H-MR Spectroscopy

Patient No.	Citrulline Peak on ¹H-MR Spectroscopy
Patient No.	NAWM	CDL	EDL
1	+	–	na
2	na	–	–
3	na	–	na
4	+	–	–
5	–	na	na
6	+	+	na
7	+	+	na
8	–	–	na
9	+	–	na
10	–	–	+
11	–	–	na
12	–	+	–
13	+	–	na
14	–	–	–
15	–	–	–
16	–	–	na
17	–	na	na
18	+	+	–
19	–	–	na
20	–	–	na
21	+	+	–
22	–	+	na
23	–	–	na
24	–	+	na
25	–	–	na
26	–	–	na
27	–	–	na

Note:—na indicates that MR spectroscopy could not be performed due to absence of such a VOI site; +, present; –, absent; MS, multiple sclerosis; VOI, voxel of interest; NAWM, normal-appearing white matter; CDL, chronic demyelinating lesions; EDL, enhanced demyelinating lesions.

Table 2:

Mean NAA/Cr, Cho/Cr, and mIns/Cr ratios obtained from the WM of healthy subjects, NAWM in MS, CDL, and EDL

VOI Site	NAA/Cr (P^* Value)	Cho/Cr (P^* Value)	mIns/Cr (P^* Value)
WM of healthy subjects	1.610	1.016	0.414
	(.704)^†	(.810)^†	(.907)^†
	(.175)^‡	(.211)^‡	(.003)^‡
	(.279)^§	(.326)^§	(.849)^§
NAWM in MS	1.560	1.033	0.411
	(.704)^*	(.810)^*	(.907)^*
	(.647)^‡	(.111)^‡	(.000)^‡
	(.845)^§	(.939)^§	(.423)^§
CDL	1.452	1.110	0.557
	(.175)^*	(.211)^*	(.003)^*
	(.647)^†	(.111)^†	(.000)^†
	(.917)^§	(.928)^§	(.097)^§
EDL	1.455	1.120	0.404
	(.279)^*	(.326)^*	(.848)^*
	(.845)^†	(.940)^†	(.423)^†
	(.917)^‡	(.928)^‡	(.097)^‡

Note:—NAA indicates N-acetylaspartate; Cr, creatine; Cho, choline; mIns, myo-inositol; WM, white matter.
* Value in comparison with the WM of healthy subjects.
† P value in comparison with the NAWM of MS.
‡ P value in comparison with CDL.
§ P value in comparison with EDL.