Neuromuscular pathology
Neuromuscular pathology is the study of muscle and neurologic disease associated with muscle dysfunction. It is a part of neuropathology.
Muscle pathology is dealt together with neurologic disease as, at the presentation, they are not infrequently impossible to definitely distinguish.
Work-up
- Clinical history, including family history.
- Laboratory studies, e.g. CK.
- Nerve conduction and electromyography studies.
- 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) |
| Fibre type grouping |
yes (d/t chronic denervation + reinnervation)[3] |
yes (???) | based on ATPase, NADH-TR stains | [1][4] |
List
Neurogenic:
- Angulated myocytes.
- Groups of small fibres.
- Apparent increase of nuclei.
Myogenic:
- Round myocytes.
- +/-Intense (darker) cytoplasm.
- +/-Fibrosis (between fibres).
- +/-Necrosis.
Detail
- Segmental demyelination - nerve/CNS abnormality.
- Axonal degeneration - nerve/CNS abnormality.
- Reinnervation - nerve injury.
- Myopathy - something is wrong with the muscle fibres.
Muscle structure/histology
Macro to micro
Organization:[5]
- Muscle - surrounded by epimysium.
- Fascicle - surrounded by perimysium.
- Muscle fibre - muscle cell.
- Myofibrils - contractile elements within the muscle cell.
- Muscle fibre - muscle cell.
- Fascicle - surrounded by perimysium.
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.
- Image: Ragged red fibres (ouhsc.edu).
- Rimmed vacuoles = inclusion body myositis.
- PAS +++ = glycogen storage disease.
- Regenerative fibres = large nuclei, basophilic cytoplasm (incr. protein synthesis, incr. RNA).
Others:
- Target fibre - "hole in middle of myofibres" = neurogenic. (???)
- Cores - central pale area along length of fibres = myopathic. (???)
- Image: Cores (ouhsc.edu).
Approach
General:
- Size variation - in groups (neurogenic) vs. singular (myogenic).
- Shape - angulated (neurogenic) vs. round (myogenic).
- Position of nuclei - peripheral (normal); central (myogenic; centronuclear myopathy[6]).
- Necrosis - suggests myogenic.
- Fibrosis - suggests myogenic.
- Inflammation - suggest myogenic vs. systemic inflammatory.
Other:
- Obvious abnormality vs. minimal change.
- Diffuse vs. focal change.
Processing of muscle biopsies
- Formulin.
- Frozen section.
- Frozen for biochemistry.
- Fragment for electronmicroscopy (glutaraldehyde fixative).
Stains for muscle biopsies
Standard
| Stain | Comment | Image |
| H&E stain | routine | [2][7] |
| Gomori trichrome | good for nemaline rods, mitochondrial pathology (appear red) |
[3] |
| PAS | glycogen storage disorders | [4][8] |
| Congo red | find amyloid; seen in inclusion body myositis |
[5][9] |
| Oil red O | lipid more in type 1 fibres |
|
| ATPase pH4.2 ATPase pH9.4 |
should have "checkerboard pattern" in normal; see table below |
[6][10] |
| NADH-TR | should have "checkerboard pattern" in normal; type 1 fibres = light blue, type 2 fibres = white |
![[2]](http://www.rvc.ac.uk/Research/Labs/NeuroLab/images/HE.jpg){kind=link}
![[3]](http://commons.wikimedia.org/wiki/File:Modified_Gomori_trichrome_stain_showing_several_ragged_red_fibers_.jpg){kind=link}
![[4]](http://neuromuscular.wustl.edu/pics/biopsy/dm/dermatopas.jpg){kind=link}
![[5]](http://neuromuscular.wustl.edu/pics/biopsy/lgd/ibmpaget/hppagetibmvaccr2.jpg){kind=link}
![[6]](http://neuromuscular.wustl.edu/pics/biopsy/dm/dermatopfatp94.jpg){kind=link}
Special - mitochondrial pathology.:
- SDH (Succinate dehydrogenase).
- COX.
- COX-SDH.
Enzymatic/genetic stuff:
- Phosphorylase.
- Adenylate deaminase.
- Acid phosphatase.
- Alkaline phosphatase.
Dunno:
- Toluidine blue - myopathies.
- Image: Nemaline rods (wustl.edu).[11]
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:
- Polymyositis.
- Inclusion body myositis.
- Dermatomyositis.
DDx
Neurogenic:
- Amyotrophic lateral sclerosis.
- Spinal muscular atrophy.
- Trauma.
- Vascular disease.
- Infective process.
- ?Motor neuron disease.
Myopathic:
- Inflammatory:
- Polymyositis.
- Inclusion body myositis.
- 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.
- Usually middle age. (???)
- Associated skin rash is common. (???)
Microscopic
Features:
- Perifascicular inflammation with perifascicular atrophy - key feature.
Inclusion body myositis
General
- Usually elderly.
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: large.
Microscopic
Features:
- Endomysial fibrosis.
- Hypercontracted fibres (large muscle fibres).
Myotonic dystrophy
Microscopic
Features:
- Internal nuclei/central nuclei.
Nemaline myopathy
General
- A type of congenital myopathy.
- Paediatric thingy.
Mitochondrial disorders
General
- Onset childhood to adulthood.
- Heteroplasmy - variable distribution of badness within affected individuals.
- Leads to "threshold effect".
Microscopic
- Trichrome most useful - find the ragged red fibres - usu. at the cell periphery.
- COX-SDH - non-staining.
EM
Features:
- Crystalloid inclusions[12]
Type 2 fibre atrophy
DDx:
- Disuse.
- Space travel.
- Steroids.
- Others.
Nerve stuff
General
- Biopsy: sural nerve.
- Myelin stain: blue = myelin.
- Gomori trichrome: axon = green, myelin = red.
See also
References
- ↑ URL: http://nmdinfo.org/lectures/info.php?id=8. Accessed on: 25 October 2010.
- ↑ URL: http://neuropathology.neoucom.edu/chapter9/chapter9fALS.html. Accessed on: 25 October 2010.
- ↑ URL: http://neuromuscular.wustl.edu/lab/mbiopsy.htm#fibertype. Accessed on: 26 October 2010.
- ↑ URL: http://missinglink.ucsf.edu/lm/ids_104_musclenerve_path/student_musclenerve/musclepath.html. Accessed on: 26 October 2010.
- ↑ URL: http://commons.wikimedia.org/wiki/File:Skeletal_muscle.jpg. Accessed on: 25 October 2010.
- ↑ URL: http://www.igbmc.fr/recherche/Dep_NG/Eq_JLaporte/JL3.html. Accessed on: 26 October 2010.
- ↑ URL: http://www.rvc.ac.uk/Research/Labs/NeuroLab/MuscleBiopsy.cfm. Accessed on: 26 October 2010.
- ↑ URL: http://neuromuscular.wustl.edu/pathol/dermmyo.htm. Accessed on: 26 October 2010.
- ↑ URL: http://neuromuscular.wustl.edu/pathol/ibmpaget.htm. Accessed on: 26 October 2010.
- ↑ URL: http://neuromuscular.wustl.edu/pathol/dermmyo.htm. Accessed on: 26 October 2010.
- ↑ URL: http://neuromuscular.wustl.edu/pathol/rod.htm. Accessed on: 26 October 2010.
- ↑ URL: http://moon.ouhsc.edu/kfung/jty1/neurotest/Q09-Ans.htm. Accessed on: 26 October 2010.
