Neuromuscular

Unknowns: Neuropathic disorders

Each of these biopsies is from a patient with a neuropathy.
What is the most likely diagnosis?

A

H & E stain

Image: Small angular muscle fibers
What are causes of small angular muscle fibers?
Answers
    Subacute partial denervation
    Type 2 muscle fiber atrophy
    Myosin-loss (Critical illness) myopathy
    Inclusion body myopathies

What stains are useful in this differential diagnosis?
Answers
  ATPase
    Denervation: Small fibers of both types
    Type 2 atrophy: Smallest fibers are type 2
    Myosin loss: ATPase pH 9.4 shows muscle fibers with staining intensity less than type 1
      H&E: Small angular fibers have large nuclei
  Non-specific esterase & NADH stain of small fibers: Denervation dark; Type 2 atrophy pale

B

ATPase pH 9.4 stain
What disease most commonly produces this pattern of muscle fiber types & size changes?

Image: Region of grouped atrophy with muscle fibers of mixed types
Answer: Amyotrophic lateral sclerosis
    Multiple small regions of grouped atrophy
    Fibers in area of grouped atrophy commonly have varied types.

C

NADH-TR stain
What processes produce this anatomical change in muscle fibers?
What muscle most frequently shows this change?
Could these be cores?

Image: Rounded clear regions with dark rim & internal regions of staining
Answers: Targets
    Most sensitive stains: NADH; COX; SDH; Caveolin-3
    Occur with: Subacute denervation, possibly with some reinnervation; Tenotomy
    Especially common in the gastrocnemius muscle
    Often have darker rims and central staining regions, but cores do not

D

ATPase pH 9.4 stain
What disease processs most commonly produces this pattern of muscle fiber types & size changes?

Image
    Large grouped atrophy
    Large muscle fibers: Predominantly type 1
    Small fibers: Mixed type

Answers: Spinal muscular atrophy
    Small fibers in SMA may be mostly type 2 or of mixed type
    Other causes of chronic partial denervationgwith reinnervation may also produce this pattern

E

VvG stain
What is this structure (arrow)?
What stains best visualize it?

Answer: Polyglucosan body
    Polyglucosan bodies in terminal axons in muscle are non-specific.
    They are most easily seen on VvG stain.
    The swellings are positively staind by PAS.
    Diseases that cause polyglucosan bodies and other axonal swellings

F

H & E stain
What is this dark stained structure (arrow)?
Answer: Pyknotic nuclear clump

How did it develop?
Answer: A muscle fiber that is so severely atrophied that only its pyknotic (dark shrunken) nuclei remain.

What disorders can produce it?
Answers
    Chronic denervation of a muscle fiber without reinnervation
        Neuropathies, chronic
        Myasthenia gravis: Under-treated
    Myotonic dystrophy
    General: Pyknotic nuclear clumps suggest a neuropathy but are not specific for denervation.


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3/11/2014