CASE 15941 Published on 22.07.2018

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (melas) syndrome: a 2 year follow-up

Section

Neuroradiology

Case Type

Clinical Cases

Authors

Andrés Cárdenas, MD; Silvia Cárdenas, MD.

Diagnóstico Maipú; Av. Maipú 1668 1638 Buenos Aires, Argentina; Buenos Aires University. Email:andresco1988@gmail.com

Patient

4 years, female

Categories

Area of Interest Neuroradiology brain ; Imaging Technique MR, MR-Spectroscopy, MR-Diffusion/Perfusion

Procedure Teleradiology, Complications, Technical aspects ; Special Focus Metabolic disorders ;

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Clinical History

A 4-year-old female with recent and progressive bilateral sensorineural hearing loss, extrapyramidal symptoms and hyperlactacidaemia, came to our institution and a MRI was performed. She returned two years later for a control with right anacusia, left hearing loss and strength and motility deterioration. A second MRI was performed.

Imaging Findings

The first MRI, no significant findings are found in the morphological sequences; However, spectroscopy shows moderate increase of the lactic acid peak. On the second MRI, brain atrophy is observed. T2 and FLAIR images reveal abnormal hyperintensity with cortical and juxtacortical involvement over both cerebral hemispheres. They are located predominantly on both sides of the parasagittal convexity, perisylvian and perirolandic areas, as well as in the inferior and medial occipital cortical regions. These lesions have high signal on diffusion-weighted images (DWI), with variable values in the apparent diffusion coefficient (ADC). The spectroscopy again reveals a lactate peak although to a lesser degree.

Discussion

Mitochondrial diseases (MD) are a heterogeneous group of disorders with symptoms of organ dysfunction across multiple body systems and occur when alteration of mitochondrial respiratory chain complex function caused by genetic mutation produces a detectable disease state [1]. Clinical features manifest typically in tissues with the highest energy requirements including skeletal muscles, brain, myocardium, and endocrine systems [2]. Several distinct MD syndromes have been described, comprising mitochondrial encephalomyopathy and lactic acidosis stroke-like episodes [3, 4, 5]. Clinically it presents with signs and symptoms of encephalomyopathies, growth disturbance, seizures, and stroke-like events that might be reversible or irreversible with permanent neurologic deficits [6, 7]. Muscle biopsies reveal the presence of ragged red fiber.
MRI remains the main imaging technique to evaluate metabolic disorders [8]. In an acute episode the disease appears on CT as hypodense cortical areas usually located in one or both parieto-occipital lobes and not confined to single vascular territory [9]. On MR, T2 hyperintense lesions may appear with a predilection for the cerebral cortex rather than underlying white matter. These lesions migrate over time, and have some predilection to occipital and parietal lobes [10, 11]. Progressive atrophy of the basal ganglia with calcifications, temporal- parietal-occipital cortex with preservation of hippocampal, entorhinal structures, and multifocal basal ganglia, deep white matter hyperintensities are chronic manifestations [12].
DWI shows high signal during acute episode, with variable ADC [13, 14]. Recent studies suggest that the development of cytotoxic oedema as represented by decreased ADC is likely due to initial neuronal energy insufficiency. Subsequent development of extracellular oedema in surrounding region leads to increased ADC signal [15].
MR spectroscopy shows a characteristic large lactate peak at 1.3 ppm [16], usually reflects anaerobic metabolism, though it has been reported to occur even in the normal-appearing brain [17]. Lactate peak has also been associated with increased disease severity and reduced survival. Elevated lactate in affected regions of the brain tends to gradually resolve as these lesions evolve further into cerebral atrophy [16].

There is no specific treatment for individuals with MELAS. Therapeutic compounds may ameliorate symptoms in individual cases; however, the available therapeutic interventions are not able to affect the essential progression of this disease. Some of the most frequently prescribed agents include ubidecarenone, idebenone, edaravone, levoarginine [18], complex B vitamins, vitamin C, E and levocarnitine.

Think MELAS in patient with acute "stroke-like" cortical lesion that crosses usual vascular territories.

Written informed patient consent for publication has been obtained.

Differential Diagnosis List

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (melas) syndrome

Ischaemic stroke

Kawasaki disease

Leigh’s disease

Status epilepticus

Myoclonic epilepsy with ragged-red fibres

Final Diagnosis

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (melas) syndrome

References

[1] Chinnery PF (1993) Mitochondrial disorders overview. GeneReviews (PMID: 20301403)

[2] Parikh S, Goldstein A, Koenig MK, et al. (2014) Practice patterns of mitochondrial disease physicians in North America. Part 1: diagnostic and clinical challenges. Mitochondrion 14(1):26–33 (PMID: 23891656)

[3] Valk J, van der Knaap (2005) MS: Mitochondrial encephalopathy with lactic acidosis, and stroke-like episodes. in Valk J, van der Knaap MS (eds): Magnetic Resonance of Myelination, and Myelin Disorders.Berlin, Germany, Springer-Verlag, 2005 pp 204-211

[4] Barkovich AJ (2005) Toxic and metabolic brain disorders. in Barkovich AJ (ed): Pediatric Neuroimaging (ed 4). New York, Raven Press pp 76-189.

[5] Iizuka T, Sakai F. (2005) Pathogenesis of stroke-like episodes in MELAS: analysis of neurovascular cellular mechanisms. Curr Neurovasc Res 2(1):29–45. (PMID: 16181098)

[6] Barkovich AJ, Good WV, Koch TK, et al (1993) Mitochondrial disorders: Analysis of their clinical and imaging characteristics. AJNR Am J Neuroradiol 14:1119-1137 (PMID: 8237691)

[7] Johnson EC, West TW, Ko NU, Strober JB. (2011) A 41-year-old man with new headache and altered mental status. Neurohospitalist 1(1): 48–54. (PMID: 23983837)

[8] Wang YX, Le WD. (2015) Progress in Diagnosing Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes. Chin Med J (Engl) 128(13):1820–5. (PMID: 26112726)

[9] Kim IO, Kim JH. (1996) Mitochondrial myopathy-encephalopathy-lactic acidosis and stroke-like episodes (MELAS) syndrome: CT and MR findings in seven children. AJR Am J Roentgenol 166(3):641–45. (PMID: 8623642)

[10] Malhotra Konark, Liebeskind David S (2016) Imaging of MELAS. Current pain and headache reports 20 (9), 54. (PMID: 27477183)

[11] Goodfellow JA, Dani K, Stewart W, Santosh C, McLean J, Mulhern S, et al. (2012) Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes: an important cause of stroke in young people. Postgrad Med J 88(1040):326–34. (PMID: 22328278)

[12] Moroni I, Bugiani M, Bizzi A, Castelli G, Lamantea E, Uziel G (2002) erebral white matter involvement in children with mitochondrial encephalopathies. Neuropediatrics 33(2):79–85 (PMID: 12075488)

[13] Wang XY, Noguchi K, Takashima S, Hayashi N, Ogawa S, Seto H. (2003) Serial diffusion-weighted imaging in a patient with MELAS and presumed cytotoxic oedema. Neuroradiology 45(9):640–3. (PMID: 12898076)

[14] Yoneda M, Maeda M, Kimura H, Fujii A, Katayama K, Kuriyama M. (1999) Vasogenic edema on MELAS: a serial study with diffusion-weighted MR imaging. Neurology 53(9):2182–4. (PMID: 10599803)

[15] Kim JH, Lim MK, Jeon TY, Rha JH, Eo H, Yoo SY, 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 (PMID: 21228936)

[16] Abe K, Yoshimura H, Tanaka H, et al (2004) Comparison of conventional and diffusion-weighted MRI and proton MR spectroscopy in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like events. Neuroradiology 46(2):113–17. (PMID: 14673554)

[17] Moller HE, Kurlemann G, Putzler M, Wiedermann D, Hilbich T, Fiedler B. (2005) Magnetic resonance spectroscopy in patients with MELAS. J Neurol Sci 229–230:131–9. (PMID: 15760631)

[18] Koga Y, Akita Y, Nishioka J, Yatsuga S, Povalko N, Katayama K et al (2007) MELAS and L-arginine therapy. Mitochondrion 7(1-2):133-9. (PMID: 17276739)

Case information

URL:	https://eurorad.org/case/15941
DOI:	10.1594/EURORAD/CASE.15941
ISSN:	1563-4086

License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Figure 1

AXIAL FLAIR, T2 and DIFFUSION weighted MR images don't show relevant abnormal signal or important structural changes.

Multi-voxel spectroscopy (TE 144 ms), at the level of the left basal ganglia reveals an inverted peak at 1.33 ppm, a finding that is characteristic of lactate accumulation.

Figure 2

Second study

AXIAL T2 FLAIR images show abnormal hyperintensity with cortical and juxtacortical involvement predominantly on both sides of the hemispheric parasagittal convexity, perisylvian and perirolandic areas, as well as the inferior and medial occipital cortical regions.

AXIAL and CORONAL T2-weighted MR images show mild to moderate prominence of the sulci and slight dilatation of ventricles.

AXIAL-DWI shows hyperintensities with low ADC value on both sides of the cortical hemispheric parasagittal convexity and perirolandic areas, and high signal with high ADC value on inferior and right medial occipital cortical region.

Spectrum from MR spectroscopy performed with an echo time of 144 msec with the voxel placed over the region of interest (left basal ganglia) reveals slight increase of inverted lactate peak.