On-Line Table 2: Cortical Gyri, Subgyral Regions, and Deep Paren

On-line Table 1: Clinical diagnostic criteria for MELAS syn- On-line Table 2: Cortical gyri, subgyral regions, and deep paren- drome (Yatsuga et al,1 2012)a chymal structures assessed for the presence of new lesions in Clinical Diagnostic Criteria patients with MELAS syndrome Category A criteria Regions Assessed Headaches with vomiting Temporal lobe Parietal lobe Seizures Superior temporal gyrus Postcentral gyrus: medial-third Hemiplegia Middle temporal gyrus Postcentral gyrus: middle-third Cortical blindness Inferior temporal gyrus Postcentral gyrus: lateral-third Acute focal lesions on neuroimaging Lingual gyrus: anterior Superior parietal lobule Category B criteria Fusiform gyrus Supramarginal gyrus High plasma or CSF lactate Hippocampal gyrus Angular gyrus Mitochondrial abnormalities on muscle biopsy: ragged-red Temporal pole Parietal operculum ﬁbers, strongly succinate dehydrogenase–reactive blood Temporal operculum Paracentral lobule: posterior vessels Precuneus A MELAS-related pathogenic variant on genetic testing: most common is MT-TL1 m.3243A.G (80% of cases) Frontal lobe Occipital lobe a A clinical diagnosis of MELAS can be made in an individual with at least 2 cate- Precentral gyrus: medial-third Cuneus: inferior: pericalcarine gory A and 2 category B criteria. Precentral gyrus: middle-third Cuneus: superior Precentral gyrus: lateral-third Lingual gyrus: posterior Paracentral lobule: anterior Superior occipital gyrus Superior frontal gyrus Middle occipital gyrus Middle frontal gyrus Inferior occipital gyrus Inferior frontal gyrus Occipital pole Lateral orbital gyri Medial orbital gyri Gyrus rectus Frontopolar cortex Medial frontal gyrus Insula: long gyrus Insula: short gyri Frontal operculum

Limbic lobe Basal ganglia Hippocampus Caudate: head Amygdala Caudate: body Fornix Caudate: tail Cingulate gyrus: anterior Putamen Cingulate gyrus: posterior Globus pallidus Hypothalamus Thalamus: anterior Thalamus: dorsal Thalamus: ventral Thalamus: pulvinar

Posterior fossa Midbrain: tegmentum Midbrain: tectum Pons Medulla oblongata Superior cerebellar peduncle Middle cerebellar peduncle Inferior cerebellar peduncle Cerebellar vermis Dentate nucleus Cerebellar hemisphere

AJNR Am J Neuroradiol :2020 www.ajnr.org E1 On-line Table 3: Anatomic location of 41 new lesions in 8 patients with MELAS Anatomic Location No. of Lesions Function and BA Total 41 From 17 MRI studies Cortical lesions 36 Lobe Parietal 11 Occipital 10 Frontal 9 Temporal 6 Limbic 2 Gyrus/component involved Pericalcarine cuneus 5 Primary visual cortex: BA 17 Postcentral gyrus: middle-third (anterior 5 Primary somatosensory cortex (hand/arm region): BA 3 cortical surface) Cerebellar folia: posterior lobe 3 Coordination of muscle movement Superior temporal gyrus 3 Primary auditory cortex: BA 41 and 42 Precentral gyrus: middle-third 2 Primary motor cortex (hand/arm region): BA 4 Precentral gyrus: lateral-third 2 Primary motor cortex (facial region): BA 4 Occipital pole 2 Primary visual cortex: BA 17 Inferior occipital gyrus 2 Secondary visual cortex: BA 18 Lingual gyrus: anterior 2 Perirhinal cortex (visual perception/memory): BA 35 Superior parietal lobule 2 Spatial orientation: BA 5 Angular gyrus 2 Reading, number processing, attention: BA 39 Middle frontal gyrus 2 Dorsolateral prefrontal cortex: BA 46 Medial frontal gyrus 2 Supplementary motor cortex and frontal eye ﬁelds: BA 6 and 8 Cingulate gyrus: posterior 2 Default mode network, emotion-memory interaction: BA 31 Fusiform gyrus 1 Facial recognition: BA 37 Precuneus 1 Visuomotor coordination: BA 7 Lingual gyrus: posterior 1 Secondary visual cortex: BA 18 Paracentral lobule: anterior 1 Primary motor cortex (leg region): BA 4 Deep lesions 5 Ventral posterolateral thalamus 4 Spinothalamic tract relay to sensory cortex Red nucleus 1 Gait, arm swinging Symmetric new lesions 6 Studies Symmetric lesions present in 6 of the 11 studies that demonstrated multiple new lesions Pericalcarine cuneus 1 Pair Postcentral gyrus: middle-third 1 Pair Precentral gyrus: middle-third 1 Pair Precentral gyrus: lateral-third 1 Pair Superior temporal gyrus 1 Pair Middle frontal gyrus 1 Pair

E2 Bhatia 2020 www.ajnr.org