Article Figures & Data
Figures
- Fig 1.
MR imaging. Axial FLAIR T2 images from 2 of the 7 patients with MNGIE at the supra- and infratentorial levels. Case 1 does not show any infratentorial involvement, while a more diffuse supra- and infratentorial signal intensity increase can be seen in case 5.
- Fig 2.
Proton MR spectroscopy. A, Axial FLAIR T2-weighted image shows the localization of the 8-cm3 1H-MR spectroscopy volume of interest in the left parieto-occipital white matter in case 5. Proton MR spectra from the VOI in case 5 (B) and in a healthy control (C). The relative content of metabolites is similar in the patient and healthy subject. Note the higher level of noise in the patient and smaller metabolite peaks.
- Fig 3.
Histologic features of brain vessels in patient 7 with MNGIE. A, Representative image of a penetrating arteriole showing increased collagen deposition in the tunica media (arrow) (H&E, original magnification ×40). B, Loss of smooth-muscle cells of the tunica media in a penetrating vessel, especially evident at the outermost layer (smooth-muscle actin, original magnification ×40). C, A thick fibrous coat completely replaces the 3-layer structure of a penetrating vessel (PicroSirius Red, original magnification ×40). D, Fibrous replacement is associated with luminal narrowing in a small brain vessel (PicroSirius Red, original magnification ×40). E, Perl iron stain consistent with hemosiderin deposits close to a brain capillary (Perls stain, original magnification ×40). F, Perivascular gliosis (glial fibrillary acidic protein, original magnification ×40).
- Fig 4.
The mtDNA amount in the brain of patient 7 with MNGIE. A, mtDNA amount in smooth-muscle and endothelial cells microdissected by laser capture from an MNGIE brain and controls (n = 3) (expressed as mtDNA copy per nucleus). B, The mtDNA amount in different cerebral regions microdissected by laser capture from MNGIE and controls (n = 3) (expressed as mtDNA copy per nucleus). SN indicates substantia nigra; CTR, controls.
Tables
Case No. Age at MRI (yr)/Sex TYMP Mutationa Mutation Type TP Activity Age at Neurologic Onset Age at Gastroenterologicb Onset 1 23/F c.1249 dupC Frame shift Undetectable 20 yr (ptosis/CPEO) Childhood 2 29/F c.1160–2A>G and c.1382_1383insC Splice defect Frame shift Undetectable Childhood (CPEO) Childhood 3 28/M c.215–1G>A and c.328C>T Splice defect p. Q110X Undetectable 24 yr (ptosis/CPEO) 20 yr 4 27/F c.1160–1G>A Splice defect Very low 20 yr (ptosis/CPEO) Childhood 5 38/M c.522T>A Splice defect Undetectable 37 yr (ptosis/CPEO) 30 yr 6 25/M c.1160–1G>A Splice defect Very low 25 yr (peripheral neuropathy) 19 yr 7 36/M c.457G>A p. G153S Undetectable Childhood (ptosis) 25 yr - Table 2:
1H-MRS white matter parieto-occipital metabolite absolute concentrations, ratios, and water signal intensity, and T2 values in patients with MNGIE and healthy controls
Patients with MNGIE (n = 7) (mean ± SD) Healthy Controls (n = 9) (mean ± SD) P Valuea Metabolite concentrations (mM) NAA 6.98 ± 0.79 9.81 ± 0.94 <.001a,c Cr 4.15 ± 0.48 5.97 ± 0.55 <.001a,c Cho 1.53 ± 0.23 1.89 ± 0.24 .01a mIns 4.46 ± 1.14 5.44 ± 0.76 .06a Metabolite ratios NAA/Cr 1.85 ± 0.18 1.80 ± 0.11 .57b Cho/Cr 0.39 ± 0.06 0.33 ± 0.04 .04b mIns/Cr 0.99 ± 0.27 0.85 ± 0.08 .16b Water signal (a.u.) SBW (0) (14.0 ± 9.0)×1010 (10.8 ± 2.0)×1010 .370 SCSF (0) (4.0 ± 7.5)×1010 (1.3 ± 0.6)×1010 .23a T2 water T2BW (ms) 112 ± 24 75 ± 8 .001a,c T2CSF (ms) 520 ± 185 776 ± 344 .098a Note:—a.u. indicates arbitrary units; SBW (0) and SCSF (0), water signals corresponding to brain and cerebrospinal water, respectively; T2BW and T2CSF, water relaxation times corresponding to brain and cerebrospinal water, respectively.
↵a Statistical significance was set at P < .0125 after Bonferroni correction for multiple comparisons.
↵b Statistical significance was set at P < .0167 after Bonferroni correction for multiple comparisons.
↵c Significant.
ROI MD (Mean ± SD) FA (Mean ± SD) AD (Mean ± SD) RD (Mean ± SD) PO-WM MNGIE 1.09 ± 0.16 0.27 ± 0.05 1.40 ± 0.16 0.93 ± 0.16 Controls 0.79 ± 0.05 0.40 ± 0.02 1.14 ± 0.07 0.61 ± 0.05 P Valuea <.0001b <.0001b .0001b <.0001b OR MNGIE 1.15 ± 0.20 0.41 ± 0.07 1.69 ± 0.19 0.88 ± 0.21 Controls 0.81 ± 0.05 0.59 ± 0.09 1.35 ± 0.12 0.54 ± 0.06 P Valuea <.0001b .0003b .0002b <.0001b PLIC MNGIE 0.78 ± 0.06 0.61 ± 0.07 1.40 ± 0.06 0.47 ± 0.08 Controls 0.69 ± 0.05 0.70 ± 0.04 1.36 ± 0.11 0.35 ± 0.05 P Valuea .0019b .0008b 0.36 .0003b CC MNGIE 0.88 ± 0.08 0.66 ± 0.06 1.64 ± 0.11 0.49 ± 0.10 Controls 0.81 ± 0.09 0.76 ± 0.06 1.72 ± 0.19 .35 ± 0.08 P Valuea .12 .0012b 0.37 .0028b
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