mtRNA Leu (MTTL1) A3243G mutations: Pathology

MELAS Syndromes

Patient Ages: 2nd & 3rd decades

Muscle Pathology

Muscle fibers
Perimysial vessels

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

Mitochondrial Proliferation: Scattered muscle fibers with Increased SDH staining

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

Mitochondrial Proliferation: Scattered muscle fibers with Increased COX staining

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

MELAS: SDH staining of intramuscular vessels is Increased

Succinic dehydrogenase (SDH) stain
  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

Brain pathology in MELAS

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.

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