Advertisement

Reversible cerebral artery constriction accompanied with stroke-like episode in MELAS: A case series

  • Author Footnotes
    1 These authors contributed equally to this work.
    Yuying Zhao
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
    Xiaolin Yu
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Geriatric Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
    Search for articles by this author
  • Kunqian Ji
    Affiliations
    Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
    Search for articles by this author
  • Yan Lin
    Affiliations
    Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
    Search for articles by this author
  • Xuebi Xu
    Affiliations
    Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
    Search for articles by this author
  • Wei Wang
    Affiliations
    Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
    Search for articles by this author
  • Chuanzhu Yan
    Correspondence
    Corresponding author at: Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107 West Wenhua Road, Jinan, Shandong 250012, China.
    Affiliations
    Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China

    Mitochondrial Medicine Laboratory, Qilu Hospital (Qingdao), Shandong University, Qingdao, Shandong 266035, China

    Brain Science Research Institute, Shandong University, Jinan, Shandong 250012, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.

      Highlights

      • Segmental stenosis of major cerebral arteries was found at acute phase of MELAS.
      • SLE lesions were located within the stenotic arteries territory.
      • Dilation at distal portions of the stenotic arteries was also observed.
      • Stenosis was resolved after the acute stage of SLE.
      • Reversible constriction of cerebral arteries may participate in SLE of MELAS.

      Abstract

      Objective

      The pathophysiology of stroke-like episode (SLE) in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) was uncertain, though mitochondrial metabolic crisis of cortical neurons and mitochondrial proliferation in small vessels of brain have been considered. However, the involvement of major cerebral vessels was debated. We aimed to investigate whether major cerebral vessels participate in SLE.

      Methods

      We retrospectively collected the clinical and neuroimaging data of MELAS patients diagnosed in our center. Through follow-up, the cases harboring reversible cerebral artery constriction on brain magnetic resonance angiography (MRA) examination were included in this study.

      Results

      There were 20 patients with intact brain MRA data at acute and non-acute phases. Only 3 cases with m.3243A > G mutation were enrolled. They suffered once or twice SLEs manifesting headache, blurred vision, seizures or mental and behavior disorder. New lesions were present in temporo-parietal and/or temporo-occipital regions. Segmental stenosis at middle cerebral artery and/or posterior cerebral artery, proximal portions in particular, was ipsilateral to the lesions at acute phase in all the 3 patients, which was resolved during the subacute or chronic stages. Moreover, the SLEs lesions were located within the stenotic arteries territory. In addition, dilation at distal portions of the stenotic arteries was observed at acute phase as well in 2 patients.

      Conclusion

      Reversible constriction of cerebral arteries may contribute to SLE of MELAS. MELAS should be a differential diagnosis when stenosis of major cerebral vessels is present at acute phase of SLE.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Yatsuga S.
        • Povalko N.
        • Nishioka J.
        • et al.
        MELAS: a nationwide prospective cohort study of 96 patients in Japan.
        Biochim. Biophys. Acta. 2012; 1820: 619-624
        • Yeh H.L.
        • Chen Y.K.
        • Chen W.H.
        • et al.
        Perfusion status of the stroke-like lesion at the hyperacute stage in MELAS.
        Brain and Development. 2013; 35: 158-164
        • Iizuka T.
        • Sakai F.
        • Suzuki N.
        • et al.
        Neuronal hyperexcitability in stroke-like episodes of MELAS syndrome.
        Neurology. 2002; 59: 816-824
        • Ohama E.
        • Ohara S.
        • Ikuta F.
        • et al.
        Mitochondrial angiopathy in cerebral blood vessels of mitochondrial encephalomyopathy.
        Acta Neuropathol. 1987; 74: 226-233
        • Noguchi A.
        • Shoji Y.
        • Matsumori M.
        • et al.
        Stroke-like episode involving a cerebral artery in a patient with MELAS.
        Pediatr. Neurol. 2005; 33: 70-71
        • Yoshida T.
        • Ouchi A.
        • Miura D.
        • et al.
        MELAS and reversible vasoconstriction of the major cerebral arteries.
        Intern. Med. 2013; 52: 1389-1392
        • Li Y.
        • Xu W.
        • Sun C.
        • et al.
        Reversible dilation of cerebral macrovascular changes in MELAS episodes.
        Clin. Neuroradiol. 2019; 29: 321-329
        • Minobe S.
        • Matsuda A.
        • Mitsuhashi T.
        • et al.
        Vasodilatation of multiple cerebral arteries in early stage of stroke-like episode with MELAS.
        J. Clin. Neurosci. 2015; 22: 407-408
        • Goto Y.
        • Nonaka I.
        • Horai S.
        A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies.
        Nature. 1990; 348: 651-653
        • Koga Y.
        • Povalko N.
        • Nishioka J.
        • et al.
        Molecular pathology of MELAS and L-arginine effects.
        Biochim. Biophys. Acta. 2012; 1820: 608-614
        • Rossignol R.
        • Faustin B.
        • Rocher C.
        • et al.
        Mitochondrial threshold effects.
        Biochem. J. 2003; 370: 751-762
        • Sparaco M.
        • Simonati A.
        • Cavallaro T.
        • et al.
        MELAS: clinical phenotype and morphological brain abnormalities.
        Acta Neuropathol. 2003; 106: 202-212
        • Zhang Z.Q.
        • Niu S.T.
        • Liang X.H.
        • et al.
        Vascular involvement in the pathogenesis of mitochondrial encephalomyopathies.
        Neurol. Res. 2010; 32: 403-408
        • Takahashi S.
        • Tohgi H.
        • Yonezawa H.
        • et al.
        Cerebral blood flow and oxygen metabolism before and after a stroke-like episode in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).
        J. Neurol. Sci. 1998; 158: 58-64
        • Ikawa M.
        • Yoneda M.
        • Muramatsu T.
        • et al.
        Detection of preclinically latent hyperperfusion due to stroke-like episodes by arterial spin-labeling perfusion MRI in MELAS patients.
        Mitochondrion. 2013; 13: 676-680
        • Tay S.H.
        • Nordli Jr., D.R.
        • Bonilla E.
        • et al.
        Aortic rupture in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes.
        Arch. Neurol. 2006; 63: 281-283
        • Koga Y.
        • Akita Y.
        • Junko N.
        • et al.
        Endothelial dysfunction in MELAS improved by l-arginine supplementation.
        Neurology. 2006; 66: 1766-1769
        • El-Hattab A.W.
        • Almannai M.
        • Scaglia F.
        Arginine and citrulline for the treatment of MELAS syndrome.
        J Inborn Errors Metab Screen. 2017; 5
        • Naini A.
        • Kaufmann P.
        • Shanske S.
        • et al.
        Hypocitrullinemia in patients with MELAS: an insight into the “MELAS paradox”.
        J. Neurol. Sci. 2005; 229-230: 187-193
        • El-Hattab A.W.
        • Emrick L.T.
        • Hsu J.W.
        • et al.
        Impaired nitric oxide production in children with MELAS syndrome and the effect of arginine and citrulline supplementation.
        Mol. Genet. Metab. 2016; 117: 407-412
        • Koga Y.
        • Povalko N.
        • Inoue E.
        • et al.
        Therapeutic regimen of L-arginine for MELAS: 9-year, prospective, multicenter, clinical research.
        J. Neurol. 2018; 265: 2861-2874
        • Yatsuga S.
        • Fujita Y.
        • Ishii A.
        • et al.
        Growth differentiation factor 15 as a useful biomarker for mitochondrial disorders.
        Ann. Neurol. 2015; 78: 814-823
        • Ji X.
        • Zhao L.
        • Ji K.
        • et al.
        Growth differentiation factor 15 is a novel diagnostic biomarker of mitochondrial diseases.
        Mol. Neurobiol. 2017; 54: 8110-8116
        • Fukuda M.
        • Nagao Y.
        Dynamic derangement in amino acid profile during and after a stroke-like episode in adult-onset mitochondrial disease: a case report.
        J. Med. Case Rep. 2019; 13: 313
        • Takahashi N.
        • Shimada T.
        • Murakami Y.
        • et al.
        Vascular involvement in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes.
        Am J Med Sci. 2005; 329: 265-266
        • Vattemi G.
        • Marini M.
        • Ferreri N.R.
        • et al.
        Overexpression of TNF-α in mitochondrial diseases caused by mutations in mtDNA: evidence for signaling through its receptors on mitochondria.
        Free Radic. Biol. Med. 2013; 63: 108-114
        • Singhal A.B.
        • Topcuoglu M.A.
        • Fok J.W.
        • et al.
        Reversible cerebral vasoconstriction syndromes and primary angiitis of the central nervous system: clinical, imaging, and angiographic comparison.
        Ann. Neurol. 2016; 79: 882-894
        • Zhu K.
        • Li S.
        • Chen H.
        • et al.
        Late onset MELAS with m.3243A > G mutation and its association with aneurysm formation.
        Metab. Brain Dis. 2017; 32: 1069-1072
        • Mancuso M.
        • Montano V.
        • Orsucci D.
        • et al.
        Mitochondrial m.3243A > G mutation and carotid artery dissection.
        Mol Genet Metab Rep. 2016; 9: 12-14
        • Iizuka T.
        • Goto Y.
        • Miyakawa S.
        • et al.
        Progressive carotid artery stenosis with a novel tRNA phenylalanine mitochondrial DNA mutation.
        J. Neurol. Sci. 2009; 278: 35-40
        • Finsterer J.
        • Zarrouk-Mahjoub S.
        Macroangiopathy is a typical phenotypic manifestation of MELAS.
        Metab. Brain Dis. 2017; 32: 977-979