Cortical venous disease severity in MELAS syndrome correlates with brain lesion development
Tóm tắt
MELAS syndrome is a mitochondrial disorder typified by recurrent stroke-like episodes, seizures, and progressive brain injury. Abnormal mitochondria have been found in arterial walls implicating a vasculogenic etiology. We have observed abnormal cortical vein T2/FLAIR signal in MELAS patients, potentially representing wall thickening and sluggish flow. We sought to examine the relationship of hyperintense veins and brain lesions in MELAS. Imaging databases at two children’s hospitals were searched for brain MRIs from MELAS patients. Artifact, sedated exams, and lack of 2D–T2/FLAIR sequences were exclusion criteria. Each exam was assigned a venous score based on number of T2/FLAIR hyperintense veins: 1 = <10, 2 = 10 to 20, 3 = >20. Cumulative brain lesions and venous score in MELAS and aged-matched normal exams were compared by Mann-Whitney test. A total of 106 exams from 14 unique MELAS patients (mean 16 ± 3 years) and 30 exams from normal aged-matched patients (mean 15 ± 3 years) were evaluated. Median venous score between MELAS and control patients significantly differed (3 versus 1; p < 0.001). In the MELAS group, venous score correlated with presence (median = 3) or absence (median = 1) of cumulative brain lesions. In all 8 MELAS patients who developed lesions, venous hyperintensity was present prior to, during, and after lesion onset. Venous score did not correlate with brain lesion acuity. Abnormal venous signal correlates with cumulative brain lesion severity in MELAS syndrome. Cortical venous stenosis, congestion, and venous ischemia may be mechanisms of brain injury. Identification of cortical venous pathology may aid in diagnosis and could be predictive of lesion development.
Tài liệu tham khảo
Goto T, Nonaka I, Harai S (1990) A mutation in the tRNA leu (UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 348:651–653
DiMauro S, Hirano M (2001) MELAS. GeneReviews® [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK1233/. Updated 21 Nov 2013
Demarest ST, Whitehead MT, Turnacioglu S, Pearl PL, Gropman AL (2014) Phenotypic analysis of epilepsy in the mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes-associated mitochondrial DNA A3243G mutation. J Child Neurol 29(9):1249–1256
Hirano RE, Koenigsberger MR, Defendini R, Pavlakis SG, DeVivo DC, DiMauro S, Rowland LP (1992) MELAS: an original case and clinical criteria for diagnosis. Neuromuscul Disord 2:125–135
Yatsuga S, Povalko N, Nishioka J, Katayama K, Kakimoto N, Matsuishi T, Kakuma T, Koga Y, Taro Matsuoka for MELAS Study Group in Japan (2012) MELAS: a nationwide prospective cohort study of 96 patients in Japan. Biochim Biophys Acta 1820:619–624
Malhotra K, Liebeskind DS (2016) Imaging of MELAS. Curr Pain Headache Rep 20(9):54
Tschampa HJ, Urbach H, Greschus S, Kunz WS, Kornblum C (2013) Neuroimaging characteristics in mitochondrial encephalopathies associated with the m.3243A>G MTTL1 mutation. J Neurol 260(4):1071–1080
Lorenzoni PJ, Werneck LC, Kay CS, Silvado CE, Scola RH (2015) When should MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) be the diagnosis? Arq Neuropsiquiatr 73(11):959–967
Kaufmann P, Engelstad K, Wei Y et al (2011) Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. Neurology 77(22):1965–1971
Barkovich AJ, Good WV, Koch TK, Berg BO (1993) Mitochondrial disorders: analysis of their clinical and imaging characteristics. AJNR Am J Neuroradiol 14:1119–1137
Friedman SD, Shaw DW, Ishak G, Gropman AL, Saneto RP (2010) The use of neuroimaging in the diagnosis of mitochondrial disease. Dev Disabil Res Rev 16(2):129–135
Matthews PM, Tampieri D, Berkovic SF et al (1991) Magnetic resonance imaging shows specific abnormalities in the MELAS syndrome. Neurology 41:1043–1046
Kim JH, Lim MK, Jeon TY et al (2011) Diffusion and perfusion characteristics of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode) in thirteen patients. Korean J Radiol 12(1):15–24
Li R, Xiao HF, Lyu JH, Wang, JJD, Ma L, Lou X (2016) Differential diagnosis of mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) and ischemic stroke using 3D pseudocontinuous arterial spin labeling. J Magn Reson Imaging
Wang Z, Xiao J, Xie S, Zhao D et al (2012) MR evaluation of cerebral oxygen metabolism and blood flow in stroke-like episodes of MELAS. J Neurol Sci 323(1–2):173–177
Ohama E, Ohara S, Ikuta F, Tanaka K, Nishizawa M, Miyatake T (1987) Mitochondrial angiopathy in cerebral blood vessels of mitochondrial encephalomyopathy. Acta Neuropathol 74(3):226–233
Mizukami K, Sasaki M, Suzuki T et al (1992) Central nervous system changes in mitochondrial encephalomyopathy: light and electron microscopic study. Acta Neuropathol 83(4):449–452
Gilchrist JM, Sikirica M, Stopa E, Shanske S (1996) Adult-onset MELAS. Evidence for involvement of neurons as well as cerebral vasculature in strokelike episodes. Stroke 27(8):1420–1423
Sparaco M, Simonati A, Cavallaro T et al (2003) MELAS: clinical phenotype and morphological brain abnormalities. Acta Neuropathol 106(3):202–212
Bonneville F (2014) Imaging of cerebral venous thrombosis. Diagn Interv Imaging 12:1145–1150
Toyoda K, Ida M, Fukuda K (2001) Fluid-attenuated inversion recovery intraarterial signal: an early sign of hyperacute cerebral ischemia. AJNR Am J Neuroradiol 22(6):1021–1029