Neuromuscular pathology

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Neuromuscular pathology is the study of muscle and neural-muscle pathologies.

Muscle pathology is dealt together with neurologic disease as, at the presentation, they after not infrequently not possible to definitely distinguish.

Work-up

  1. Clinical history, including family history.
  2. Laboratory studies, e.g. CK.
  3. Nerve conduction and electromyography studies.
  4. Muscle biopsy.

Patterns

Overview

 
 
 
 
 
 
 
 
Neuromuscular
pathology
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Neurogenic
 
 
Myogenic
 
 
Other/Mixed
Neurogenic Myogenic Notes Image
Shape of fibres angulated round round fibres[1]
Small fibres groups
("group atrophy") 		singular group atrophy[2]
Large fibres
 No +/-Scattered "hypercontracted fibres" DMD (WC)

List

Neurogenic:

  • Angulated myocytes.
  • Groups of small fibres.
  • Apparent increase of nuclei.

Myogenic:

  • Round myocytes.
  • +/-Intense (darker) cytoplasm.
  • +/-Fibrosis (between fibres).
  • +/-Necrosis.

Detail

  1. Segmental demyelination - nerve/CNS abnormality.
  2. Axonal degeneration - nerve/CNS abnormality.
  3. Reinnervation - nerve injury.
  4. Myopathy - something is wrong with the muscle fibres.

Muscle structure/histology

Macro to micro

Organization:[3]

  • Muscle - surrounded by epimysium.
    • Fascicle - surrounded by perimysium.
      • Muscle fibre - muscle cell.
        • Myofibrils - contractile elements within the muscle cell.

Fibre types

 
 
 
Types
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Type 1
slow twitch
 
 
 
Type 2
fast twitch

List

Type 1 - AKA slow twitch:

  • Predominantly oxidative metabolism, i.e. have lots of mitochondria.

Type 2 - AKA fast twitch:

  • Predominantly glycolytic metabolism.

Mnemonic Slow red fat ox: Slow twitch fibres are (grossly) more red (due to mitochondria), lipid rich (fat) and primarily have oxidative metabolism.

Abnormal findings

  • Ragged red fibres = mitochondrial pathology.
  • Rimmed vacuoles = inclusion body myositis.
  • PAS +++ = glycogen storage disease.

Approach

General:

  1. Size variation - in groups (neurogenic) vs. singular (myogenic).
  2. Shape - angulated (neurogenic) vs. round (myogenic).
  3. Position of nuclei.
  4. Necrosis - suggests myogenic.
  5. Fibrosis - suggests myogenic.
  6. Inflammation.

Other:

  1. Obvious abnormality vs. minimal change.
  2. Diffuse vs. focal change.

Processing of muscle biopsies

  1. Formulin.
  2. Frozen section.
  3. Frozen for biochemistry.
  4. Fragment for electronmicroscopy (glutaraldehyde fixative).

Stains for muscle biopsies

Common/standard:

  • H&E stain.
  • Gomori trichrome - Good for nemaline rods, mitochondrial pathology (red).
  • PAS.
  • Congo red - find amyloid; seen in inclusion body myositis.
  • Oil Red O - type 1 more lipid.
  • ATPase - should have checkerboard pattern in normal.
  • NADH-TR - should have checkerboard pattern in normal.

Special - mitochondrial pathology.:

  • SDH.
  • COX.
  • COX-SDH.

Enzymatic/genetic stuff:

  • Phosphorylase.
  • Adenylate deaminase.
  • Acid phosphatase.
  • Alkaline phosphatase.

Dunno:

  • Toluidine blue.

IHC:

  • Dystrophy panel.
  • Lymphocytic markers (CD45, CD3, CD4, CD8, CD20).
  • MAC - inclusion body myositis.
  • APP - inclusion body myositis.
  • Ubquitin - inclusion body myositis.

ATPase stain pattern/fibre type

Type 1
slow twitch 		Type 2
fast twitch
pH 4.2 dark light
pH 9.4 light dark

Inflammatory myopathy

DDx:

  1. Polymyositis.
  2. Inclusion body myositis.
  3. Dermatomyositis.

DDx

Neurogenic:

  • Amyotrophic lateral sclerosis.
  • Spinal muscular atrophy.
  • Trauma.
  • Vascular disease.
  • Infective process.
  • ?Motor neuron disease.

Myopathic:

  • Inflammatory:
    1. Polymyositis.
    2. Inclusion body myositis.
    3. Dermatomyositis.
  • Duchenne muscular dystrophy.
  • Becker muscular dystrophy.
  • Limb-girdle muscular dystrophy.
  • Myotonic dystrophy.
  • Metabolic - glycogen storage disease.

Other:

  • Myasthenia gravis.
  • Mitochondrial myopathy.
  • Congenital fibre type disproportion.
  • Periodic paralysis.

Amyotrophic lateral sclerosis

General

  • Abbreviated ALS.
  • Affects - corticospinal tract - gliosis.

Microscopic

Features:

  • Neurogenic pattern:
    • Group atrophy.
    • +/-Target fibre.

Dermatomyositis

General

  • Complement mediated disease... membrane attach complex.

Microscopic

Features:

  • Perifascicular inflammation with perifascicular atrophy - key feature.

Inclusion body myositis

Microscopic

Features:

  • Inflammation.
  • Vacuolated fibres (with proteineous aggregates) - key feature.

DDx: polymyositis.

IHC: APP +ve, ubiquitin +ve, tau +ve.

Polymyositis

General

  • Tx: steroids.

Microscopic

Features:

  • Inflammation.

DDx: Inclusion body myositis.

Muscular dystrophy

General

  • DDx: lots.

Microscopic

Features:

  • Endomysial fibrosis.
  • Hypercontracted fibres (large muscle fibres).

References

  1. ↑ URL: http://nmdinfo.org/lectures/info.php?id=8. Accessed on: 25 October 2010.
  2. ↑ URL: http://neuropathology.neoucom.edu/chapter9/chapter9fALS.html. Accessed on: 25 October 2010.
  3. ↑ URL: http://commons.wikimedia.org/wiki/File:Skeletal_muscle.jpg. Accessed on: 25 October 2010.
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