Profiles of paediatric patients experiencing stroke-like episodes associated with mitochondrial disease

Gülhan Karakaya Molla^1*Özlem Ünal Uzun²Khanim Baba Zada³Emine Genç⁴Zümrüt Arslan Gülten⁵Tarık Yıldırım⁶Aydan Ersoy⁷Belkıs Ak⁸Aliye Gülbahçe⁹Sevil Yıldız¹⁰Nafiye Emel Çakar¹¹Meryem Karaca⁸Tanyel Zubarioglu³Burcu Öztrük Hişmi¹²Şahin Erdöl¹³Hasan Önal¹⁴Bülent Kara¹⁵GÜLDEN GOKÇAY⁸

• ¹Departmet of Child Health and Diseases Child Metabolism,, Tekirdag City Hospital, Tekirdag, Türkiye
• ²Department of Child Health and Diseases Child Metabolism, Kocaeli Universitesi Tip Fakultesi, Izmit, Türkiye
• ³Department of Child Health and Diseases Child Metabolism, Istanbul Universitesi-Cerrahpasa Cerrahpasa Tip Fakultesi, Fatih, Türkiye
• ⁴Department of Child Health and Diseases Child Metabolism, Marmara Universitesi Tip Fakultesi, Istanbul, Türkiye
• ⁵Departement of Child Health and Diseases Child Metabolism, TC Saglik Bakanligi Sisli Hamidiye Etfal Egitim ve Arastirma Hastanesi, Şişli, Türkiye
• ⁶Department of Child Health and Diseases Child Metabolism, TC Saglik Bakanligi Basaksehir Cam ve Sakura Sehir Hastanesi, Başakşehir, Türkiye
• ⁷Department of Child Health and Diseases Child Metabolism, Bursa Uludag Universitesi Tip Fakultesi, Nilüfer, Türkiye
• ⁸Department of Child Health and Diseases Child Metabolism, Istanbul Universitesi Istanbul Tip Fakultesi, Istanbul, Türkiye
• ⁹Department of Child Health and Diseases Child Metabolism, Kocaeli şehir Hastanesi, Kocaeli, Türkiye
• ¹⁰Department of Child Health and Diseases Child Metabolism, TC Saglik Bakanligi SBU Bursa Yuksek Ihtisas Egitim ve Arastirma Hastanesi, Bursa, Türkiye
• ¹¹Department of Child Health and Diseases Child Metabolism, TC Saglik Bakanligi Adiyaman Istanbul Prof Dr Cemil Tascioglu Sehir Hastanesi, Istanbul, Türkiye
• ¹²Marmara Universitesi Tip Fakultesi, Istanbul, Türkiye
• ¹³Bursa Uludag Universitesi Tip Fakultesi, Nilüfer, Türkiye
• ¹⁴TC Saglik Bakanligi Basaksehir Cam ve Sakura Sehir Hastanesi, Başakşehir, Türkiye
• ¹⁵Department of Child Health and Diseases Child Neurology, Kocaeli Universitesi Tip Fakultesi, Izmit, Türkiye

ABSTRACT Introduction: Stroke-like episodes (SLE) are defined as events characterized by the sudden onset of neurological symptoms with clinical manifestations similar to those of a stroke. However, they are distinguished by the presence of radiological lesions that do not conform to single vascular territory. MELAS syndrome, which is characterized by metabolic encephalopathy, lactic acidosis, and SLE, has been identified as the first genetically defined and most widely known mitochondrial cause of SLE. It has been demonstrated that SLE may occur in the course of a variety of mitochondrial diseases, including those that are the result of nuclear DNA mutations. Objective: In this retrospective, multicenter, observational cohort study, we sought to determine the clinical, radiological, EEG, and genetic characteristics of patients with mitochondrial gene mutations presenting with SLE and the frequency and treatment of SLE. Methods: Thirty-four patients with a genetically diagnosed mitochondrial disease from 9 paediatric metabolic disease centres in the Marmara Region of Turkey were included in the study, of whom 13 pateints had SLEs. Demographic characteristics, symptoms, clinical features, cranial MRI, EEG findings, and genetic characteristics were evaluated. Conclusion: In this study, stroke-like episodes in genetically defined mitochondrial disorders were most frequently observed in MELAS and POLG mutations, and rarely in CoQ10 deficiency, Leigh syndrome cases. Cranial MRI findings are often frontotemporal in location and inconsistent with vascular distribution, and focal epileptiform activity on EEG are diagnostically significant. In MELAS, clinical improvement was observed in patients when L-arginine was initiated in the acute period. The findings emphasise that SLE should be evaluated in the differential diagnosis of sudden onset neurological symptoms in mitochondrial diseases.