Black Toenail Sign in MELAS Syndrome

Whitehead, Matthew T.; Wien, Michael; Lee, Bonmyong; Bass, Nancy; Gropman, Andrea

doi:10.1016/j.pediatrneurol.2017.06.017

Cited by 20 publications

(11 citation statements)

References 26 publications

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“…Less commonly, there were reversible lesions that did not restrict acutely or undergo volume loss. The reversible pattern is well-described in early MELAS imaging literature (transient "fleeting" cortical lesions), [4][5][6]20,22 but our more common pattern of intracortical necrosis is increasingly recognized 10,[17][18][19]23,36 and may reflect earlier imaging with enhanced sequence protocols across time. Reversible lesions may represent limited neuronal damage that does not reach the threshold for irreversible cell damage.…”

Section: Cortical Laminar Necrosis and Temporal Evolutionmentioning

confidence: 99%

“…10,15,16 In the subacute phase, cortical lesions may develop T2 hypointensity ("black toenail sign") and T1 gyriform hyperintensity, in keeping with cortical laminar necrosis. [17][18][19] In the chronic stage, gyral infarcts evolve into areas of encephalomalacia, volume loss, and progressive multifocal cerebral and cerebellar atrophy, with associated cognitive decline. 3 Symmetric basal ganglia calcifications have also been described.…”

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confidence: 99%

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Acute Cortical Lesions in MELAS Syndrome: Anatomic Distribution, Symmetry, and Evolution

Bhatia

Krishnan

Kortman

et al. 2019

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder affecting children and young adults. Stroke-like episodes are often associated with acute cortical lesions in the posterior cerebral cortex and are classically described as asymmetric and transient. In this study we assessed the anatomic distribution of acute cortical lesions, the incidence of symmetry, and the temporal evolution of lesions. MATERIALS AND METHODS:This was a retrospective cohort study of patients who had a confirmed genetic diagnosis of a pathogenic variant associated with MELAS and MR imaging performed at our center (2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018). Each MR imaging study was assessed for new lesions using T1, T2, FLAIR, DWI, ADC, and SWI. The anatomic location, symmetry, and temporal evolution of lesions were analyzed.RESULTS: Eight patients with the same pathogenic variant of MELAS (MT-TL1 m.3243A.G) with 31 MR imaging studies were included. Forty-one new lesions were identified in 17 of the studies (5 deep, 36 cortical). Cortical lesions most commonly affected the primary visual cortex, the middle-third of the primary somatosensory cortex, and the primary auditory cortex. Thirty of 36 cortical lesions had acute cortical diffusion restriction, of which 21 developed cortical laminar necrosis on subacute imaging. Six of 11 studies with multiple lesions showed symmetric cortical involvement.

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Section: Cortical Laminar Necrosis and Temporal Evolutionmentioning

confidence: 99%

mentioning

confidence: 99%

Acute Cortical Lesions in MELAS Syndrome: Anatomic Distribution, Symmetry, and Evolution

Bhatia

Krishnan

Kortman

et al. 2019

AJNR Am J Neuroradiol

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“…3 This case is a pointer to the unusual presentation of MELAS with multiple movement disorders, with a learning point that black toe nail sign on brain MRI (see Fig. 2 for a better example reproduced from previously published literature) can be a diagnostic clue to MELAS 1 …”

Section: Discussionmentioning

confidence: 78%

“…1). 1 His MRI angiography, venogram, electrocardiogram, echocardiography, electroencephalography, Anti‐nuclear Antibody (ANA), and Anti‐Phospho‐Lipid Antibody (APLA) were normal. All of these pointed to a possibility of mitochondrial encephalopathy with lactic acidosis and stroke‐like episodes (MELAS) 2 .…”

Section: Case Reportmentioning

confidence: 99%

A Boy with Spells of Unusual Movements After Failure in Exam

Desai

2021

Movement Disord Clin Pract

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“…7 Conventional brain magnetic resonance imaging (MRI) findings in MELAS syndrome include stroke-like lesions (SLLs) in regions not corresponding to vascular territories, a peculiar pattern of gyral necrosis affecting the cortex and juxtacortical white matter referred to as the "black toenails sign," signal changes in pallidal nuclei, nonspecific T 2 white matter hyperintensity, and supratentorial and infratentorial brain atrophy. 16,17 The prevalence of all these features in MELAS and MSS patients remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Brain MRS correlates with mitochondrial dysfunction biomarkers in MELAS‐associated mtDNA mutations

Gramegna

Evangelisti

Vito

et al. 2021

Ann Clin Transl Neurol

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Objective: The purpose of this study was to investigate correlations between brain proton magnetic resonance spectroscopy ( 1 H-MRS) findings with serum biomarkers and heteroplasmy of mitochondrial DNA (mtDNA) mutations. This study enrolled patients carrying mtDNA mutations associated with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS), and MELAS-Spectrum Syndrome (MSS). Methods: Consecutive patients carrying mtDNA mutations associated with MELAS and MSS were recruited and their serum concentrations of lactate, alanine, and heteroplasmic mtDNA mutant load were evaluated. The brain protocol included single-voxel 1 H-MRS (1.5T) in the medial parieto-occipital cortex (MPOC), left cerebellar hemisphere, parieto-occipital white matter (POWM), and lateral ventricles. Relative metabolite concentrations of N-acetyl-aspartate (NAA), choline (Cho), and myo-inositol (mI) were estimated relative to creatine (Cr), using LCModel 6.3. Results: Six patients with MELAS (age 28 AE 13 years, 3 [50%] female) and 17 with MSS (age 45 AE 11 years, 7 [41%] female) and 39 sex-and age-matched healthy controls (HC) were enrolled. These patients demonstrated a lower NAA/ Cr ratio in MPOC compared to HC (p = 0.006), which inversely correlated with serum lactate (p = 0.021, rho = À0.68) and muscle mtDNA heteroplasmy (p < 0.001, rho = À0.80). Similarly, in the cerebellum patients had lower NAA/ Cr (p < 0.001), Cho/Cr (p = 0.002), and NAA/mI (p = 0.001) ratios, which negatively correlated with mtDNA blood heteroplasmy (p = 0.001, rho = À0.81) and with alanine (p = 0.050, rho = À0.67). Ventricular lactate was present in 78.3% (18/23) of patients, correlating with serum lactate (p = 0.024, rho = 0.58). Conclusion: Correlations were found between the peripheral and biochemical markers of mitochondrial dysfunction and brain in vivo markers of neurodegeneration, supporting the use of both biomarkers as signatures of MELAS and MSS disease, to evaluate the efficacy of potential treatments.

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Black Toenail Sign in MELAS Syndrome

Cited by 20 publications

References 26 publications

Acute Cortical Lesions in MELAS Syndrome: Anatomic Distribution, Symmetry, and Evolution

Acute Cortical Lesions in MELAS Syndrome: Anatomic Distribution, Symmetry, and Evolution

A Boy with Spells of Unusual Movements After Failure in Exam

Brain MRS correlates with mitochondrial dysfunction biomarkers in MELAS‐associated mtDNA mutations

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