MELAS Pathology

mtRNA Leu (MTTL1) A3243G mutations: Pathology

Patient Ages: 2nd & 3rd decades

Brain
Muscle

Ragged Red Fibers: Scattered

Gomori trichrome stain

Scattered fibers with clear rim

H&E stain

"Ragged red" fibers

Gomori trichrome stain

Gomori trichrome stain

Gomori trichrome stain

SDH stain

Muscle Fibers: Increased SDH stain
Scattered through muscle
Variable degrees

Muscle fiber: Increased SDH stain:
Individual mitochondria within muscle fiber are enlarged
compared to surrounding fibers

Cytochrome oxidase (COX) stain

Succinate dehydrogenase (SDH) stain

Cytochrome oxidase (COX) stain

Muscle fibers with Mitochondrial proliferation (Increased SDH stain)
Muscle fibers with increased SDH stain may also have increased COX stain

Succinic dehydrogenase (SDH) stain

Muscle fibers with increased SDH & COX stain

COX stain

Cytochrome Oxidase (COX) stain: Reduced or Increased
Muscle fibers may have reduced, normal or increased COX staining (Right)

Lipid accumulation
Increased Sudan black stain in muscle fiber
with mitochondrial proliferation

Succinic dehydrogenase (SDH) stain

MELAS
Medium-sized perimysial vessels have increased SDH staining
Contrast with normal staining in MNGIE & Control

Succinic dehydrogenase (SDH) stain

Normal: Mild SDH staining of medium sized perimysial vessels

MRIs during "stroke-like" episodes Cortical lesions (Posterior): Spares white matter Lesion location Not confined to territory of single vessel Involves only part of territory of several vessels Swelling Mutation: A3243G
FLAIR image	T2 weighted image

From: Cindy Ly

CT during episode of homonymous hemianopia
Medial occipital lesion (Arrow)	Enlarged ventricles	Late in disease course MRI: Severe involvement of occipital cortex	Temporal gray matter: Severely abnormal Temporal horn of Ventricles: Enlarged.