Original ArticleBlack Toenail Sign in MELAS Syndrome
Introduction
Mitochondrial encephalopathy with lactic acidosis and strokelike episodes (MELAS) syndrome is a mitochondrial disorder causing progressive brain injury and neurological dysfunction in the form of recurrent strokelike episodes and/or seizures in most patients. The most common mitochondrial gene defect causing MELAS is mt.3243A>G, which is present in roughly 80%.1, 2 In addition to MELAS gene mutations, diagnostic criteria include encephalopathy (early strokelike events or seizures), headache with vomiting, cortical vision loss, lactic acidosis, and focal brain lesions.3, 4, 5
Progressive posterior predominant cerebral lesions are typical in MELAS.6, 7, 8, 9, 10, 11, 12 The cortex and juxtacortical white matter are generally involved, but lesions do not tend to respect large arterial territories.6, 7, 10, 11, 12, 13, 14 Acute brain lesions are characterized by regional cortical or subcortical swelling and edema, which may either resolve or evolve into a permanent brain injury.5, 15, 16, 17 Chronically injured parenchyma shows magnetic resonance (MR) signal changes representing encephalomalacia and gliosis, and, in severe insults, coagulative necrosis. Neuronal loss, gliosis, and necrosis in the involved cortex and white matter have been confirmed histologically.11, 12, 18, 19, 20, 21, 22 Necrosis manifests signal suppression on T2-fluid attenuation inversion recovery (T2/FLAIR) sequences, with the degree of hypointensity corresponding to the degree of necrosis as the signal approaches the cerebrospinal fluid, the signal for which the FLAIR inversion pulse is targeted. This hypointense T2/FLAIR signal localizes to the deep gyral cortex and juxtacortical white matter, resembling toes with black nails. In this study, we aim to characterize the imaging features and natural history of MELAS-related gyral necrosis.
Section snippets
Materials and Methods
This retrospective study was performed after an institutional review board approval. The imaging databases from two academic children's hospitals were queried for all brain MRs from patients with MELAS syndrome performed over a 15-year span. In each case, the electronic medical record was reviewed to verify the diagnosis and to document the disease duration. Examinations lacking T2-FLAIR sequences and studies with substantial motion artifact were excluded. Studies were performed on either 1.5
Results
A total of 124 examinations from 14 unique MELAS patients (nine female, five male), with a mean age of 16 ± 3 years (range 6 to 22 years) met the inclusion criteria (Table). All patients except one had imaging at different time points with the number of follow-up studies ranging from two to 27 (two to 11-year follow-up interval). The most common clinical indications for the examinations were stroke (41 of 124), seizure (38 of 124), and headache (13 of 124). All 14 patients had a genetic
Discussion
Gyral necrosis is a common finding in MELAS syndrome. Moreover, the number of necrotic lesions correlates with the disease duration and tends to start in the posterior cerebrum without regard to large arterial territories. These gyral necroses resemble the appearance of black toenails on T2/FLAIR sequences: deep cortical/juxtacortical hypointense signals surrounded by a hyperintense signal.
Neuronal loss, necrosis, and gliosis in the involved cortex and white matter, with cortical laminar
Conclusions
The black toenail sign signifying gyral necrosis is a common imaging feature in MELAS syndrome. Gyral necrosis extent correlates with disease duration.
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2020, Journal of the Neurological SciencesCitation Excerpt :In some cases, particularly those with recurrent SLLs, SLLs end up as permanent structural lesions. These include white matter lesions (WMLs), cysts, LCN, also known as pseudolaminar necrosis, cortical or subcortical, focal atrophy, or the “toenail sign” [1,21]. LCN is characterised by gyriform T1-hyperintensity in the chronic stage [4,7,21].