Screening for MELAS mutations in young patients with stroke of undetermined origin

Abstract

Worldwide, cryptogenic strokes account for 8.3-55% of ischemic strokes in young patients [1][2][3][4][5] . It has been suggested that mitochondrial disorders may present oligosymptomatically and may be responsible for up to one third of cryptogenic ischemic strokes in the young 6 . Even though clinical features vary widely in mitochondrial diseases, distinctive syndromes such as MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) have been described [7][8][9] . Stroke-like episodes can appear at any age in MELAS and occur in around 50% of the patients with the A3243G mitochondrial DNA (mtDNA) mutation 10 . In most cases, episodes occur before the fifth decade. The occipital lobe is the most commonly affected area but the reason for this predilection is unclear 11 . The A3243G mutation has been reported in approximately 80% of cases of MELAS and other mtDNA mutations such as T3271C have also been described 12 . The degree of heteroplasmia (the proportion of normal and mutant mitochondrial DNA in each tissue) is an important factor influencing variability of phenotypical presentation.If the full-blown syndrome does not develop but mitochondrial dysfunction is present and contrib- Screening for MeLAS MutAtionS in young pAtientS with Stroke of undeterMined origin

Acute mitochondrial encephalopathy reflects neuronal energy failure irrespective of which genome the genetic defect affects

“…The MSCAE data were based on our own material (n = 36), which has been previously published (Tzoulis et al, 2006(Tzoulis et al, , 2010. Ninety-four MELAS cases were collected from the literature (n = 89) (Goto et al, 1992;DiMauro and Hirano, 1993;Takahashi et al, 1998;Watanabe et al, 1998;Yoneda et al, 1999;Ohshita et al, 2000;Oppenheim et al, 2000;Bataillard et al, 2001;Deschauer et al, 2001;Kim et al, 2001Kim et al, , 2011Iizuka et al, 2002Iizuka et al, , 2007Crimi et al, 2003;Jeppesen et al, 2003;Kolb et al, 2003;Wang et al, 2003Wang et al, , 2010Chung et al, 2005;Betts et al, 2006;Bi et al, 2006;Mizrachi et al, 2006;Tzoulis et al, 2006Tzoulis et al, , 2010Chan et al, 2007;Conforto et al, 2007;Malfatti et al, 2007;Chou et al, 2008;Ito et al, 2008;Stoquart-Elsankari et al, 2008;Hsu et al, 2009;Karkare et al, 2009;Tzoulis and Bindoff, 2009;Herrero-Martin et al, 2010;Tsujikawa et al, 2010;Glatz et al, 2011) and our own unpublished material (n = 5). This was a non-systematic review that included all large case series of patients fulfilling the clinical criteria for MELAS ...…”

“…Diabetes mellitus, heart disease and nephropathy are seen in MELAS. Acute liver necrosis occurs in POLG-related disorders either spontaneously or precipitated by the antiepileptic drug sodium valproate, but has not been reported in genetically confirmed MELAS (Goto et al, 1992;DiMauro and Hirano, 1993;Takahashi et al, 1998;Yoneda et al, 1999;Bataillard et al, 2001;Deschauer et al, 2001;Iizuka et al, 2002;Crimi et al, 2003;Jeppesen et al, 2003;Kolb et al, 2003;Wang et al, 2003Wang et al, , 2010Betts et al, 2006;Tzoulis et al, 2006Tzoulis et al, , 2010Conforto et al, 2007;Malfatti et al, 2007;Hsu et al, 2009;Tsujikawa et al, 2010;Glatz et al, 2011;Kim et al, 2011).…”

“…While high T 2 signal lesions of the thalamus are rare in MELAS, and lesions of the inferior olivary nuclei not reported, both are common features of MSCAE. Calcification of deep grey matter structures such as the caudate, lentiform and dentate nuclei is common in MELAS, but does not occur in MSCAE (Takahashi et al, 1998;Watanabe et al, 1998;Yoneda et al, 1999;Ohshita et al, 2000;Oppenheim et al, 2000;Kim et al, 2001;Wang et al, 2003;Chung et al, 2005;Bi et al, 2006;Mizrachi et al, 2006;Chan et al, 2007;Conforto et al, 2007;Iizuka et al, 2007;Chou et al, 2008;Ito et al, 2008;Stoquart-Elsankari et al, 2008;Karkare et al, 2009;Tzoulis and Bindoff, 2009;Herrero-Martin et al, 2010;Tsujikawa et al, 2010;Tzoulis et al, 2010).…”

Differenzialdiagnostik seltener Schlaganfallursachen

“…Die MR-Tomografie zeigt typischerweise Ischämien im Be-reich der okzipitalen Hirnrinde, wenngleich die Läsionen nicht auf bestimmte Versorgungsgebiete beschränkt sind [80]. Wenngleich positive Effekte der Behandlung mit Coenzym Q10 beschrieben sind [81], ist bislang keine kausale oder evidenzbasiert wirksame Therapie vorhanden.…”

23. MELAS: Clinical features, muscle biopsy and molecular genetics

“…Since its first description, few patients with this disease have been identified in Brazil [8][9][10] . In this study we analyze the clinical and laboratory manifestations, brain images, histological and molecular findings in 10 Brazilian patients suffering from MELAS.…”