View source for Neuromuscular pathology

[[Image:Vasculitic neuropathy - plastics - low mag.jpg|thumb|right|[[Micrograph]] of a nerve biopsy. [[Toluidine blue stain]].]]
'''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=
===General===
#Clinical history, including family history.
#Laboratory studies, e.g. CK.
#Nerve conduction and electromyography studies.
#Muscle / nerve biopsy.

===Clinical===
*Fasciculations - small involuntary muscle contraction, imply lower motor neuron lesion.
*Reflexes - see ''[[physical examination]]''.
*Strength. 

===Laboratory studies===
The CK suggest the type of disorder:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/NeuroHelp/ZNEWWU10.htm http://moon.ouhsc.edu/kfung/jty1/NeuroHelp/ZNEWWU10.htm]. Accessed on: 27 October 2010.</ref>
*High ~200-300X normal -- suggests ''myogenic''.
*Intermedidate ~20-30X normal -- possibly ''inflammatory''.
*Low ~2-5X normal -- possibly ''neurogenic''.

Notes:
*The CK value is most useful when it is very high.<ref name=pmid17224570>{{cite journal |author=Filosto M, Tonin P, Vattemi G, ''et al.'' |title=The role of muscle biopsy in investigating isolated muscle pain |journal=Neurology |volume=68 |issue=3 |pages=181–6 |year=2007 |month=January |pmid=17224570 |doi=10.1212/01.wnl.0000252252.29532.cc |url=}}</ref>
*Normal CK values:<ref>URL: [http://www.gpnotebook.co.uk/simplepage.cfm?ID=1436155929 http://www.gpnotebook.co.uk/simplepage.cfm?ID=1436155929]. Accessed on: 27 October 2010.</ref>
**Men: 24-195 unit/litre.
**Women: 24-170 units/litre.

===Biopsy===
====Muscle biopsies====
Indications:
* Weakness, Fatigue, Cramps
* Myopathic EMG
* Elevated CK
Not indicated: Myasthenia gravis, myotonia

* MRI to select ideal spots for biopsy.
* In chronic diseases, select a '''moderately''' affected muscle.
** Best specific muscles: Deltoid, Biceps, Quadriceps.
** Avoid areas with previous EMG analysis. 

* Tissue should be sent fresh or frozen for analysis.
** Freeze most tissue in isopentane (-160°C) immersed in liquid nitrogen. 
** Ultrastructural analyis might be required in some cases -> save something in 4% glutaraldehyde.
* [[FFPE]] specimens unsuitable for enzymatic stains.
** Useful for morphology of inflammatory cells.

====Nerve biopsies====
* Nerve procession: 3 pieces
** Frozen -> useful for acid phosphatase, congo etc..
** Formalin -> for IHC.
** 4% Glutaraldehyde fixed -> for electron microscopy.

====Skin biopsies====
* Punch biopsies (3mm) for small fiber neuropathy.
** Paraformaldehyde-lysine-periodate -> for PGP9.5 immunofluorescence.

=Muscle structure/histology=
===Macroscopic to microscopic===
Organization:<ref>URL: [http://commons.wikimedia.org/wiki/File:Skeletal_muscle.jpg http://commons.wikimedia.org/wiki/File:Skeletal_muscle.jpg]. Accessed on: 25 October 2010.</ref>
*Muscle - surrounded by epimysium.
**Fascicle - surrounded by perimysium.
***Muscle fibre - muscle cell.
****Myofibrils - contractile elements within the muscle cell.

Notes:
*This is similar for nerves:<ref>{{Ref Martini6|438}}</ref>
**Nerve (surrounded by ''epineurium'') -> Fascicle (surrounded by ''perineurium'') -> Nerve fibre (surrounded by ''endoneurium'').

===Fibre===
[[File:1022 Muscle Fibers (small).jpg|500px|right]]
====Fibre morphology====
*Small or large?
**Related to age?  Birth 15µm, 6yrs: 25-30µm, 12yrs: 45µm, adult: 50-60µm.
*Round or angular?
*Architecture: Normal, inclusions, nuclear internalization?
*Pathology distribution: Absent, focal, uniform?
**Pathologic material: Amyloid, Glycogen, Lipid?
 
====Fibre types====
{{familytree/start}}
{{familytree | | | |A11| | | | |A11 =Types           }}
{{familytree | |,|-|-|^|-|-|.|}}
{{familytree | B11 | | | | B12 |B11=Type 1<br>slow twitch|B12=Type 2<br>fast twitch }}
{{familytree/end}}

Type 1 - [[AKA]] slow twitch:
*Predominantly oxidative metabolism, i.e. have lots of mitochondria.

Type 2 - AKA fast twitch:
*Predominantly glycolytic metabolism.

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

====Table - fibre types====
<center>
{| class="wikitable sortable" 
! Parameter
! Type I 
! Type II 
|-
| Twitch speed
| slow
| fast
|-
| Colour
| red
| white
|-
| Fat content
| higher
| lower
|-
| ATP production		 
| oxidative
| anaerobic <br>glycoloysis
|- 
| Glycogen
| higher
| lower
|-
| Resistance to fatigue
| higher
| lower
|-
| ATPase quality
| lower
| higher
|-
| Myoglobin
| higher
| lower
|-
| Mitochondria
| higher
| lower
|-
| ATPase pH 9.4 stain
| light brown
| dark brown
|}

</center>

*Check for fibre type grouping or fibre type predominance.

===Normal findings===
====Muscle-tendon junction====
Features:
*Myofibrils frayed + adjacent to dense connective tissue.
**Image: [http://www.lab.anhb.uwa.edu.au/mb140/corepages/connective/Images/mtj040vg.jpg Muscle-tendon junction (anhb.uwa.edu.au)].<ref>URL: [http://www.lab.anhb.uwa.edu.au/mb140/corepages/connective/connect.htm http://www.lab.anhb.uwa.edu.au/mb140/corepages/connective/connect.htm]. Accessed on: 4 November 2010.</ref>

====Muscle-nerve junction====
Features:
*Dunno. (???)

Images:
*[http://commons.wikimedia.org/wiki/File:Skeletal_muscle_-_cross_section,_nerve_bundle.jpg MN junction - crappy image (WC)]. (???)

====Muscle spindle====
Features:
*Weird looking muscle cell. (???)

Image: [http://www.lab.anhb.uwa.edu.au/mb140/corepages/muscle/Images/mspindle041he.jpg Muscle spindle (anhb.uwa.edu.au)].<ref>URL: [http://www.lab.anhb.uwa.edu.au/mb140/corepages/muscle/muscle.htm http://www.lab.anhb.uwa.edu.au/mb140/corepages/muscle/muscle.htm]. Accessed on: 28 November 2010.</ref>

===Abnormal findings===
====Iatrogenic====
*Torn (muscle) fibres (in the process of extraction for examination):
**Membrane intact.
**Myofibril kaputt.
**No inflammation.

====Pathologic====
*Ragged red fibres = mitochondrial pathology.
**Image: [http://moon.ouhsc.edu/kfung/jty1/NeuroTest/Q71-Ans.htm Ragged red fibres (ouhsc.edu)].
*Vacuoles
**Acid maltase positive = lysosomal vacuoles.
**Rimmed vacuoles = [[inclusion body myositis]].
**Freezing artifacts (clear).
*PAS +++ = [[glycogen storage disease]].
*Nemaline rods = [[nemaline myopathy]]
**Image: [http://commons.wikimedia.org/w/index.php?title=File:Biopsy nemaline myopathy gomori.jpg]
*Cores - central pale area along length of fibres in NADH stain = central core disease. 
**Image: [http://commons.wikimedia.org/w/index.php?title=File:Central core disease NADH stain.jpg].

Others:
*Annular myofibrils ("ringbinden") = myopathic: Regeneration, myotonic dystrophy, tenotomy. Found in approx. 3% of unselected cases.
Images: [http://frontalcortex.com/?page=image&topic=1&qid=987] - HE, NADH or MAD stains are useful.
*Target fibre - "hole in middle of myofibres" = neurogenic.
**Images: [http://commons.wikimedia.org/w/index.php?title=File:Denervation_atrophy_-_very_high_mag.jpg Target fibres - very high mag. (WC)], [http://commons.wikimedia.org/wiki/File:Denervation_atrophy_-_sdh_-_very_high_mag.jpg Target fibres - SDH stain - very high mag. (WC)].
*Regenerative fibres = large nuclei, basophilic cytoplasm (incr. protein synthesis, incr. RNA).

===Approach===
General:
*Neurogenic or myopathic?
*Acute or chronic?
Check:
#Size variation - in groups (neurogenic, Dystrophinopathies) vs. singular scattered (myogenic, acute neurogenic). 
#Shape - angulated (neurogenic) vs. round (myogenic).
#Position of nuclei - peripheral (normal); central (myogenic; centronuclear myopathy<ref>URL: [http://www.igbmc.fr/recherche/Dep_NG/Eq_JLaporte/JL3.html http://www.igbmc.fr/recherche/Dep_NG/Eq_JLaporte/JL3.html]. Accessed on: 26 October 2010.</ref>).
#[[Necrosis]] & regeneration - suggests acute myogenic.
#Fibrosis - suggests chronic myogenic.
#Inflammation - suggest myogenic vs. systemic inflammatory.
#*Lymphocytes, macrophages, eosinophils - or even neoplastic?
#Fibre type predominance - suggest congenital myopathy (esp. in small type 1 fibres), demyelinating neuropathy.
Other:
#Obvious abnormality vs. minimal change.
#Diffuse vs. focal change.
#Pathology in adjacent vessels or connective tissue.

==Processing of muscle biopsies==
#[[Formalin]] fixed (formalin fixed-paraffin embedded).
#Frozen tissue for histology.
#Frozen tissue for biochemistry.
#Fragment for [[electron microscopy]] (glutaraldehyde fixed).

===SMH labeling===
*"E" = "frozens"; done on frozen tissue.
**[[IHC]] done on these.
**May have the label "2" ... even though there is no part 2.
*Blue slides = "plastics", i.e. plastic embedded.
**Stained with methylene blue.<ref>URL: [http://www.nature.com/modpathol/journal/v18/n5/full/3800344a.html http://www.nature.com/modpathol/journal/v18/n5/full/3800344a.html]. Accessed on: 26 November 2010.</ref> vs. toluidine blue. (???)
**Thin sections: 0.1 - 1 micrometres.
*Normal SMH numbering = "paraffin".

==Patterns (pathologic)==
===Overview===
{{familytree/start}}
{{familytree | | | | | | | | | A01 | | | | | |A01=Neuromuscular<br>pathology}}
{{familytree | | | | |,|-|-|-|-|+|-|-|-|-|.| |}}
{{familytree | | | | B01 | | | B02 | | | B03|B01=Neurogenic|B02=Myogenic|B03=Other/Mixed }}
{{familytree/end}}

{| class="wikitable"
|		 
| '''Neurogenic'''
| '''Myogenic'''
| Notes
| Image
|-
| Shape of fibres 
| angulated
| round
|
| [http://nmdinfo.org/lectures/wineinger/wineinger/ppt/Slide25.JPG round fibres]<ref>URL: [http://nmdinfo.org/lectures/info.php?id=8 http://nmdinfo.org/lectures/info.php?id=8]. Accessed on: 25 October 2010.</ref>
|-
| Small fibres		 
| groups <br>("group atrophy")
| singular
| 
| [http://neuropathology.neoucom.edu/chapter9/images9/13-7.jpg group atrophy]<ref>URL: [http://neuropathology.neoucom.edu/chapter9/chapter9fALS.html http://neuropathology.neoucom.edu/chapter9/chapter9fALS.html]. Accessed on: 25 October 2010.</ref>
|-
| Large fibres<br>
| no
| +/-scattered
| "hypercontracted<br>fibres"
| [http://commons.wikimedia.org/wiki/File:Duchenne-muscular-dystrophy.jpg DMD (WC)]
|-
| Fibre type<br>grouping
| yes (d/t chronic <br>denervation + <br>reinnervation)<ref>URL: [http://neuromuscular.wustl.edu/lab/mbiopsy.htm#fibertype http://neuromuscular.wustl.edu/lab/mbiopsy.htm#fibertype]. Accessed on: 26 October 2010.</ref>
| yes (???)
| based on ATPase, <br>NADH-TR stains
| [http://missinglink.ucsf.edu/lm/ids_104_musclenerve_path/student_musclenerve/subpages/ng.atp.9.4.1.html ATPase 9.4]<ref>URL: [http://missinglink.ucsf.edu/lm/ids_104_musclenerve_path/student_musclenerve/musclepath.html http://missinglink.ucsf.edu/lm/ids_104_musclenerve_path/student_musclenerve/musclepath.html]. Accessed on: 26 October 2010.</ref>, [http://moon.ouhsc.edu/kfung/JTY1/Com04/Com04Image/Com401-3-12.gif NADH-TR]<ref>URL: [http://moon.ouhsc.edu/kfung/JTY1/Com04/Com401-3-Diss.htm http://moon.ouhsc.edu/kfung/JTY1/Com04/Com401-3-Diss.htm]. Accessed on: 28 October 2010.</ref>
|}

====List====
Neurogenic:
*Angulated myocytes.
*Groups of small fibres.
*Apparent increase of nuclei.

<gallery>
File:Neurogenic atrophy muscle biopsy HE x100.jpg | Groups of atrophic fibers (HE)
File:Muscle angular atrophic fibers.jpg | Angulated atrophic fibers (HE)
File:ATPase targetoid fibers neurogenic muscle atrophy.jpg | Fiber type grouping and targetoid fibers in neurogenic atrophy (ATPase)
File:Denervation atrophy - very high mag.jpg | Type 2 fiber atrophy (HE)
File:Denervation atrophy - atp94 - high mag.jpg | Type 2 fiber atrophy (ATPase)
</gallery>

Myogenic:
*Round myocytes.
*+/-Intense (darker) cytoplasm.
*+/-Fibrosis (between fibres).
*+/-Nuclear internalization. 
*+/-Necrosis.

<gallery>
File:BMD histology.jpg | Basophilic fibers and nuclear internalization in muscular dystropy (HE).
</gallery>

===Detail===
#Segmental demyelination - nerve/CNS abnormality.
#Axonal degeneration - nerve/CNS abnormality.
#Reinnervation - nerve injury.
#Myopathy - something is wrong with the muscle fibres.

=Stains for muscle biopsies=
===Standard===
{| class="wikitable"
| '''Stain'''
| '''Comment'''
| '''Image'''
|-
| H&E stain
| routine, fibre size, shape, nuclei
| [http://www.rvc.ac.uk/Research/Labs/NeuroLab/images/HE.jpg H&E]<ref>URL: [http://www.rvc.ac.uk/Research/Labs/NeuroLab/MuscleBiopsy.cfm http://www.rvc.ac.uk/Research/Labs/NeuroLab/MuscleBiopsy.cfm]. Accessed on: 26 October 2010.</ref>, [http://commons.wikimedia.org/wiki/File:Denervation_atrophy_-_very_high_mag.jpg H&E (WC)]
|-
| Gomori trichrome
| good for nemaline rods, <br>mitochondrial pathology<br>(ragged red fibres - at edge <br>of myocyte)
| [http://commons.wikimedia.org/wiki/File:Modified_Gomori_trichrome_stain_showing_several_ragged_red_fibers_.jpg RRF (WC)]
|-
| PAS
| glycogen storage disorders
| [http://neuromuscular.wustl.edu/pics/biopsy/dm/dermatopas.jpg]<ref name=dermmyo>URL: [http://neuromuscular.wustl.edu/pathol/dermmyo.htm http://neuromuscular.wustl.edu/pathol/dermmyo.htm]. Accessed on: 26 October 2010.</ref>
|-
| Congo red 
| find [[amyloid]]; seen in<br>inclusion body myositis
| [http://neuromuscular.wustl.edu/pics/biopsy/lgd/ibmpaget/hppagetibmvaccr2.jpg]<ref name=ibmpaget>URL: [http://neuromuscular.wustl.edu/pathol/ibmpaget.htm http://neuromuscular.wustl.edu/pathol/ibmpaget.htm]. Accessed on: 26 October 2010.</ref>
|-
| Oil red O 
| lipid more in<br> type 1 fibres
| [http://moon.ouhsc.edu/kfung/jty1/Composites/FNEWWU10-lipid-storage.htm ORO]
|-
| ATPase pH4.2<br>ATPase pH9.4
| should have "checkerboard <br>pattern" in normal; see table below
| [http://neuromuscular.wustl.edu/pics/biopsy/dm/dermatopfatp94.jpg]<ref name=dermmyo>URL: [http://neuromuscular.wustl.edu/pathol/dermmyo.htm http://neuromuscular.wustl.edu/pathol/dermmyo.htm]. Accessed on: 26 October 2010.</ref>
|-
| NADH-TR 
| good for cores or tubular aggregates, should have "checkerboard <br>pattern" in normal; <br>type 1 fibres = light blue, <br>type 2 fibres = white
| [https://commons.wikimedia.org/wiki/File:Cell_sample_of_muscle_tissue_with_central_core_disease_(stained_for_contrast).jpg]
|-
| Myoadenylate deaminase
| Normal: positive, AMPDA deficiency: negative
| [https://commons.wikimedia.org/wiki/File:MAD_deficiency_enzymatic.jpg MAD deficiency]
|-
| Acid phosphatase
| Histiocytes/Macrophages, Lysosomal storage, Lipofuscin
|
|-
| Cytochrome oxidase
| Mitochondrial pathology
| [https://commons.wikimedia.org/wiki/File:Cox-deficient_fibers_in_mitochondrial_myopathy.jpg COX deficiency]
|}

===ATPase stain pattern/fibre type===
{| class="wikitable"
|		 
| '''Type 1<br>slow twitch'''
| '''Type 2<br>fast twitch'''
|-
| '''pH 4.2'''
| '''dark'''
| light
|-
| '''pH 9.4'''
| light
| '''dark'''
|}

===Special - mitochondrial pathology===
{| class="wikitable"
| '''Stain'''
| '''Comment'''
| '''Image'''
|-
|[[Succinate dehydrogenase|Succinate <br>dehydrogenase (SDH)]]
| stains mitochondria; <br>usu. +ve in mitochondrial disease<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/neurohelp/ZNEWWU10.htm http://moon.ouhsc.edu/kfung/jty1/neurohelp/ZNEWWU10.htm]. Accessed on: 2 March 2011.</ref>
| [http://moon.ouhsc.edu/kfung/JTY1/Com04/Com04Image/Com401-3-03.gif]<ref name=ouhsc1>URL: [http://moon.ouhsc.edu/kfung/JTY1/Com04/Com401-3-Diss.htm http://moon.ouhsc.edu/kfung/JTY1/Com04/Com401-3-Diss.htm]. Accessed on: 28 October 2010.</ref>, [http://commons.wikimedia.org/wiki/File:Denervation_atrophy_-_sdh_-_high_mag.jpg SDH (WC)]
|-
| Cytochrome oxidase (COX)
| stains mitochondria; <br>usu. -ve in mitochondrial disease
| [http://moon.ouhsc.edu/kfung/JTY1/Com04/Com04Image/Com401-3-09.gif]<ref name=ouhsc1>URL: [http://moon.ouhsc.edu/kfung/JTY1/Com04/Com401-3-Diss.htm http://moon.ouhsc.edu/kfung/JTY1/Com04/Com401-3-Diss.htm]. Accessed on: 28 October 2010.</ref>
|-
|COX-SDH
| used to look for mitochondrial disease
|
|}

===Enzymatic/genetic stuff===
{| class="wikitable"
| '''Stain'''
| '''Comment'''
| '''Image'''
|-
| Phosphorylase
| 
|
|-
| Adenylate deaminase
| 
| 
|-
| Acid phosphatase (ACPH)
| necrosis (red)
| 
|-
| Alkaline phosphatase (ALPH)
| regeneration (punctate - black)
| 
|}

Dunno:
*Toluidine blue - myopathies. 
**Image: [http://neuromuscular.wustl.edu/pics/biopsy/rods/rodhptb2.jpg Nemaline rods (wustl.edu)].<ref>URL: [http://neuromuscular.wustl.edu/pathol/rod.htm http://neuromuscular.wustl.edu/pathol/rod.htm]. Accessed on: 26 October 2010.</ref>

===IHC===
*Dystrophy panel.
**Dystrophin<ref name=omim310200>{{OMIM|310200}}</ref> - Duchenne muscular dystrophy (onset usu. <3 years), Becker's muscular dystrophy (onset usu. 20s or 30s).
***Membranous staining is normal.  Loss of membranous staining = pathologic.
****Tested with three antibodies -- as the protein is hueuge.
**Spectrin - a cause of long QT syndrome. (???)
*Lymphocytic markers (CD45, CD3, CD4, CD8, CD20).
*MAC - inclusion body myositis.
*APP - inclusion body myositis (?), axonal swellings.
*Ubquitin - inclusion body myositis.

*TDP-43 (also ''TDP43'') - cytoplasmic staining in IBM.
**Normally stains the nucleus.
***Same protein that that in implicated in [[ALS]] and [[frontotemporal dementia]].

=List of common conditions=
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.

=Groups of disorders=
==Inflammatory myopathy==
DDx:
#[[Polymyositis]].
#*Disease of adults.
#[[Inclusion body myositis]] (IBM).
#*Distal weakness.
#*Can be sporadic or hereditary.
#[[Dermatomyositis]].
#*Acute development.
#*May be associated with malignancy.
#[[Granulomatous myositis]].
#Graft-versus-host disease.
#Infectious myositis.
#*Rare.


'''Quick overview:'''
{| class="wikitable"
|		 
| '''Dermatomyositis'''
| '''Polymyositis'''
| '''sporadic Inclusion body myositis
|-
| Myositis type
| Perifascicular	 
| Diffuse
| Diffuse (limited inflammation)
|-
| Histology 
| Perivascular inflammation, Perifascicular damage.
| Endomysial inflammation and damage.
| Endomysial inflammation, rimmed vacuoles withe eosinophilic inclusions, neurogenic changes.
|-
| Immunostaining
| CD4+ B-cell lymphocytes predominate, C5b9 complement complex deposits in capillaries.
| CD8+ lymphocytes invading non-necrotic fibers.
| Mainly CD8-positive lymphocytes.
|-
| Electron microscopy
| Tubulovesicular inclusions.
| Nothing special.
| Filamentous inclusions.
|-
| Exemplary image
|[[File:Dermatomyositis_muscle_biopsy_HE.jpg | center | thumb]]
|[[File:Polymyositis_muscle_biopsy_HE.jpg | center | thumb]]
|[[File:IBM rimmed vacuoles HE x200.jpg | center | thumb]]
|}

===Partial invasion of muscle fibres===
DDx:<ref name=inflam_wustledu>URL: [http://neuromuscular.wustl.edu/pathol/inflammation.htm#cellinv http://neuromuscular.wustl.edu/pathol/inflammation.htm#cellinv]. Accessed on: 3 November 2010.</ref>
*[[Polymyositis]].
*[[Inclusion body myositis]] (IBM).

Images:
*[http://neuromuscular.wustl.edu/pathol/inflammation.htm#cellinv Partial invasion of muscle fibres (wustl.edu)].<ref name=inflam_wustledu>URL: [http://neuromuscular.wustl.edu/pathol/inflammation.htm#cellinv http://neuromuscular.wustl.edu/pathol/inflammation.htm#cellinv]. Accessed on: 3 November 2010.</ref>

==Muscular dystrophy==
===General===
*DDx: large.

A short DDx:
*Duchenne's muscular dystrophy.<ref name=omim310200>{{OMIM|310200}}</ref>
*Becker's muscular dystrophy.
*Limb-girdle muscular dystrophy.
**Lotsa different mutations, autosomal dominant and recessive variants.
*Myotonic dystrophy.<ref name=omim160900>{{OMIM|160900}}</ref><ref name=omim602668>{{OMIM|602668}}</ref>

===Microscopic===
Features:
*Endomysial fibrosis.
*Hypercontracted fibres (large muscle fibres).

<gallery>
File:BMD histology.jpg | Becker's muscular dystrophy ([[H&E]))
File:Dys1 Dystrophinopathy carrier.jpg | Carrier status in dystrophinophathy (Dystrophin)
</gallery>

Images:
*[http://path.upmc.edu/cases/case161.html Becker muscular dystrophy (upmc.edu)].
*[http://path.upmc.edu/cases/case234/micro.html Myotonic dystrophy - several images (upmc.edu)].

==Limb-girdle muscular dystrophy==
===General===
*A group of muscular dystrophies with childhood or adult onset.<ref>URL: [http://www.ncbi.nlm.nih.gov/books/NBK1408/ http://www.ncbi.nlm.nih.gov/books/NBK1408/]. Accessed on: 25 November 2010.</ref>
*Rare.
*Usually autosomal recessive.
*Treatment: none; supportive only.

===Subtypes===
*Sarcoglycanopathy.
*Calpainopahty.
*Dysferlinopathy.

Notes:
*Can be demonstrated with [[IHC]].

===DDx===
*DMD gene associated MDs (Duchenne MD, Becker MD).
*Facioscapulohumeral muscular dystrophy (FSHD).
*Emery-Dreifuss MD (EDMD).
*Congenital MD (CMD).
*Inflammatory myopathies.

<gallery>
File:LGMD2D alpha sarcoglycan.jpg | Loss of alpha sarcocglycan in LGMD2D (WC).
</gallery>


==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 (???).
**Peripheral blue accumulation in occasional cells.

===EM===
Features:
*Crystalloid inclusions.<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/neurotest/Q09-Ans.htm http://moon.ouhsc.edu/kfung/jty1/neurotest/Q09-Ans.htm]. Accessed on: 26 October 2010.</ref>
*"Ballooned" mitochondria; loss of cristae -- loss of membranous folds within mitochrondrion.

<gallery>
File:Ragged red fibres - gtc - very high mag.jpg | ragged red fibers (Gomöri Trichrom)
Cox-deficient_fibers_in_mitochondrial_myopathy.jpg | Cox-deficient fibers (blue) in mitochondrial myopathy (COX-SDH stain)
File:Mitochondrial_myopathy_crystalline_inclusions.jpg | Crystalline inclusions in the mitochondria (Electron microscopy)
</gallery>

==Type 2 fibre atrophy==
===General===
DDx:
*Disuse.
*Space travel.
*Steroids.
*Others.

===Microscopic===
Features:
*Atrophy for type 2 atrophy.

====Images====
<gallery>
Image:Denervation_atrophy_-_high_mag.jpg | Denervation atrophy - high mag. (WC)
Image:Denervation_atrophy_-_atp94_-_intermed_mag.jpg | Type 2 fibre atrophy - ATPase pH 9.4 - intermed. mag. (WC)
Image:Denervation_atrophy_-_atp94_-_high_mag.jpg | Type 2 fibre atrophy - ATPase pH 9.4 - high mag. (WC)
</gallery>

=Specific entities=
==Amyotrophic lateral sclerosis==
{{Main|Amyotrophic lateral sclerosis}}
*Abbreviated ''ALS''.
===General===
*Abbreviated ''ALS''.
*Affects - corticospinal tract - gliosis.

===Microscopic===
Features:
*Neurogenic pattern:
**Group atrophy.
**+/-Target fibres.

==Dermatomyositis==
:''For the skin manifestations see: [[Inflammatory_skin_disorders#Dermatomyositis]]''.
===General===
*Complement mediated disease - membrane attack complex.
*Usually middle age. 
*Associated skin rash is common.
**May precede or follow muscle pathology.
*Associated with malignancy in approximately 10% of cases.<ref name=pmid20398365>{{cite journal |author=Chen YJ, Wu CY, Huang YL, Wang CB, Shen JL, Chang YT |title=Cancer risks of dermatomyositis and polymyositis: a nationwide cohort study in Taiwan |journal=Arthritis Res. Ther. |volume=12 |issue=2 |pages=R70 |year=2010 |pmid=20398365 |pmc=2888225 |doi=10.1186/ar2987 |url=}}</ref>

====Clinical====
*If the characteristic skin lesions are absent... it is likely ''idiopathic inflammatory myositis'' and related to ''[[diabetes mellitus]]''.<ref name=pmid20536597>{{cite journal |author=Limaye VS, Lester S, Blumbergs P, Roberts-Thomson PJ |title=Idiopathic inflammatory myositis is associated with a high incidence of hypertension and diabetes mellitus |journal=Int J Rheum Dis |volume=13 |issue=2 |pages=132–7 |year=2010 |month=May |pmid=20536597 |doi=10.1111/j.1756-185X.2010.01470.x |url=}}</ref>

===Microscopic===
Features:
*Perifascicular inflammation with perifascicular atrophy - '''key feature'''.
*Loss of vessels around muscle fibres.
**Vessels should be where more than 3 or more fibres are opposed to one another.

====Images====
<gallery>
Image:Dermatomyositis_-_intermed_mag.jpg | Dermatomyositis - intermed. mag. (WC) 
Image:Dermatomyositis_-_high_mag.jpg | Dermatomyositis - high mag. (WC)
File:Dermatomyositis HE x40.jpg | Dermatomyositis - low mag. (WC)
File:NP MGMT 0252.jpg | Dermatomyostits (WC/jensflorian)
File:Dermatomyositis c5b9.jpg | C5b9 complex deposits in dermatomyositis (WC)
</gallery>

===EM===
*Endothelial tubuloreticular inclusions (abbrev. ''TRIs'') - undulating tubules in the smooth ER, usu. perinuclear;<ref name=pmid19330338>{{cite journal |author=Stoltenburg-Didinger G, Genth E |title=[Dermatomyositis] |language=German |journal=Z Rheumatol |volume=68 |issue=4 |pages=287–94 |year=2009 |month=June |pmid=19330338 |doi=10.1007/s00393-008-0398-y |url=}}</ref> not pathognomonic - may be seen in inclusion body myositis.<ref name=pmid20569678>{{cite journal |author=Katzberg HD, Munoz DG |title=Tubuloreticular inclusions in inclusion body myositis |journal=Clin. Neuropathol. |volume=29 |issue=4 |pages=262–6 |year=2010 |pmid=20569678 |doi= |url=}}</ref>

Images:
*[http://moon.ouhsc.edu/kfung/jty1/Com/Com310-1-Diss.htm Tubulorecticular inclusions (ouhsc.edu)].

====DDx:====
* Anti-Jo1 myositis
* Paraneoplastic myositis

==Inclusion body myositis==
===General===
*Usually elderly. 
*Thought to be related to Alzheimer's disease due to similar staining with congo red and several [[IHC]] stains.<ref name=pmid8579968>{{cite journal |author=Askanas V, Engel WK |title=New advances in the understanding of sporadic inclusion-body myositis and hereditary inclusion-body myopathies |journal=Curr Opin Rheumatol |volume=7 |issue=6 |pages=486–96 |year=1995 |month=November |pmid=8579968 |doi= |url=}}</ref>

===Microscopic===
Features:
*Inflammation.
*Vacuolated muscle fibres (with proteineous aggregates) - '''key feature'''.
**Vacuolation = "inclusion".
***Usually in the centroidal location.

DDx: 
*[[Polymyositis]].

===IHC=== 
Features:<ref name=pmid8579968/>
*Congo red +ve.
*APP +ve, ubiquitin +ve, tau +ve. (???)

===EM===
*Inclusion bodies - tubulovescicular material.<ref>URL: [http://neuromuscular.wustl.edu/pathol/ibm.htm http://neuromuscular.wustl.edu/pathol/ibm.htm]. Accessed on: 3 November 2010.</ref>

<gallery>
File:IBM rimmed vacuoles HE x200.jpg | Rimmed vacuoles in inclusion body myositis (HE).
</gallery>

==Polymyositis==
===General===
*Tx: steroids.

===Microscopic===
Features:<ref name=ouhsc_znn>URL: [http://moon.ouhsc.edu/kfung/jty1/neurohelp/ZNN0TA01.htm http://moon.ouhsc.edu/kfung/jty1/neurohelp/ZNN0TA01.htm]. Accessed on: 25 February 2012.</ref>
*Lymphocytes - may be in large clusters.
**"Partial invasion" - lymphocytes within the muscle fibres - '''key feature'''.
*Regenerating fibres with enlarged nuclei.

DDx: 
*[[Inclusion body myositis]].
*[[Dermatomyositis]].

<gallery>
File:Neuropathology case XII 01.jpg | Polymoysitis ([[H&E]])
File:Neuropathology case XII 02.jpg | Polymoysitis ([[H&E]])
File:Neuropathology case XII 03.jpg | Polymoysitis (CD45)
File:Neuropathology case XII 04.jpg | Polymoysitis (MHC-I)
File:Polymyositis_HE.jpg | Polymoysitis ([[H&E]])
</gallery>

Images:
*[http://neuromuscular.wustl.edu/pathol/inflammation.htm#cellinv Focal invasion of lymphocytes (wustl.edu)].

===IHC===
Features:<ref name=ouhsc_znn>URL: [http://moon.ouhsc.edu/kfung/jty1/neurohelp/ZNN0TA01.htm http://moon.ouhsc.edu/kfung/jty1/neurohelp/ZNN0TA01.htm]. Accessed on: 25 February 2012.</ref>
*T cells > B cells.
**Endomysial - T cells.
**Perimysial - B cells.



==Granulomatous myositis==
===General===
Etiology:<ref>{{Cite journal  | last1 = Prieto-González | first1 = S. | last2 = Grau | first2 = JM. | title = Diagnosis and classification of granulomatous myositis. | journal = Autoimmun Rev | volume = 13 | issue = 4-5 | pages = 372-4 | month =  | year =  | doi = 10.1016/j.autrev.2014.01.017 | PMID = 24424169 }}</ref>
* [[Sarcoidosis]].
* Idiopathic.
* Infectious ([[Tuberculosis]], Syphillis, Brucellosis.
* Foreign-body reaction.
* [[Thymoma]] - myasthenia gravis.
* [[Lymphoma]] - paraneoplastic.
* [[Primary biliary cholangitis]].

<gallery>
File:Sarkoidosis muscle.jpg | Sarcoidosis ([[H&E]])
File:Granulomatous myositis.jpg | Granulomatous myositis ([[H&E]])
</gallery>


==Spinal muscular atrophy==
* Autosomal recessive disease by SMN1 gene deletion on chromosome 5q.
* Centromeric gene copy (SMN2) whose product can mitigate disease severity.
* Variability in severity and age of onset of disease (SMA type 1-4).
* Neurogenic muscle atrophy, weakness, loss of reflexes, tongue fasciculation and tremor.
** Usu. groups of atrophic fibers.
** Few compensatorirc hypertrophic fibers.
===Diagnostic relevance===
* Antisense-oligonucleotide that increase full-length protein product derived from SMN2 (Nusinersen).
* Gene transfer with scAAV9-SMN (Zolgensma).

==Metabolic myopathy==
===Microscopic===
Fetures:
*Intramuscular storage deposits.
** PAS positive stain in glycogen storage disease.

<gallery>
File:PAS glycogen storage disease intermed mag.jpg | Glycogen storage (PAS).
File:Trichrom glycogen storage disease intermed mag..jpg | Glycogen storage (Trichrom).
File:Vacuolar myopathy mcArdle type V glcogenosis.jpg | Type V glocogenosis (McArdle, HE).
</gallery>

==Myotonic dystrophy==
===Microscopic===
Features:
*Internal nuclei/central nuclei.

==Nemaline myopathy==
===General===
*A type of congenital myopathy.
*Paediatric thingy.
*May appear secondary in other lesions.
*Rods are seen in trichrome stain
<gallery>
File:Biopsy nemaline myopathy gomori.jpg | Nemaline rods (Trichrom Gomöri).
File:Congenital nemaline myopathy.jpg | Congenital nemaline myopathy (Trichrom Gomöri).
</gallery>


==Central core myopathy==
===General===
*Floppy infant, but stable clinial course.
*Autosomal dominant inheritance.
**Mutation in RYR1
**Predisposition for malignant hyperthermia.
*Normal CK levels.
*Non-pathologic EMG.

*Cores visile in NADH staining.
**Mostly centrally, but can be eccentric.

<gallery>
File:Central core disease NADH stain.jpg | Cores (NADH stain).
File:Cell sample of muscle tissue with central core disease (stained for contrast).jpg | Cores (NADH TR stain).
</gallery>

==Centronuclear myopathy==
*AKA myotubular myopathy
*Several types
** X-chromosomal recessive: floppy infant
** austosmal dominant: late onset with proximal involvement, ptosis, opthalmoplegia

<gallery>
File:Biopsy centronuclear myopathy HE.jpg
</gallery>

Image centronuclear myopathy<ref>URL: [http://www.igbmc.fr/recherche/Dep_NG/Eq_JLaporte/JL3.html http://www.igbmc.fr/recherche/Dep_NG/Eq_JLaporte/JL3.html]. Accessed on: 26 October 2010.</ref>).

==Drug-induced rhabdomyolysis==
*AKA ''drug-induced acute necrotizing myopathy''.

===General===
Clinical:<ref name=pmid15021204>{{Cite journal  | last1 = Coco | first1 = TJ. | last2 = Klasner | first2 = AE. | title = Drug-induced rhabdomyolysis. | journal = Curr Opin Pediatr | volume = 16 | issue = 2 | pages = 206-10 | month = Apr | year = 2004 | doi =  | PMID = 15021204 }}</ref>
*Myalgias. 
*Myoglobinuria.
*Increased elevated serum creatine kinase (CK).

Causes:
*Ecstasy (MDMA).
*Statins.

===Microscopic===
Features:
*Muscle [[necrosis]].
**Fibre collapse = increased staining on [[H&E stain|H&E]], [[HPS stain|HPS]].
**Karyolysis - loss of nuclei.
**Macrophage (phagocytosis) clean-up = pale moth-eaten appearance (seen well on [[PAS stain|PAS]]).
*No inflammation.
*No perifascicular atrophy.

Images:
*[http://path.upmc.edu/cases/case184/micro.html Drug-induced rhabdomyolysis - several images (upmc.edu)].

===Stains===
*PAS +ve fibres (macrophages).

===IHC===
*CD45 -ve (no lymphocytes).

===EM===
*Negative for [[tubuloreticular inclusions]].

==Trichinosis==
:See ''[[Microorganisms]]''.
Parasitic disease classically associated with consumption of uncooked pork.

=Nerve stuff=
===General===
*Most common biopsy: sural nerve.
**Approx. 20-30% of the biopsies are diagnostic or may alter treatment decisions.
** Far less common: Superficial peroneal nerve.
*Metabolic, toxic and nutritional causes account for 50% of neuropathies.
*Inflammatory neuropathies (mostly GBS, CIDP or vasculitis): 10-20%.
*Familial neuropathy: 10-20%.
*Neoplasm-associated neuropathy: 5-10%.

===Nerve structure===
*Nerve (surrounded by epineurium).
*Fascicle (surrounded by perineurium).
** Usu 6-15 fascicles in sural nerve.
*Nerve fibre (surrounded by endoneurium).
**Myelinated axons.
**Unmyelinated axons and their Schwann cells together are called Remak bundles.

Epineurium:
* Capillaries, arterioles and venules.
* Fibroblasts (CD34+/-ve, EMA-ve, S100-ve).
* Macrophages (CD68+ve, CD168+ve).
* Mast cells (metachromatic granules).
* Leukocytes (usu. less than 10 CD3+ve Lymphocytes/mm²). 
* Pacinian corpuscles (no pathological relevance).

Perineurium:
* Fascicles may separated by perineurial septae.
*Occasional perineurial calcifications (no pathological relevance).
*Renaut bodies (subperineurial whorled structures consisting of fibroblasts).

<gallery>
Image:N_renaut_body_semithin.jpg|Renaut body in a fascicle.
File:Pacinian Corpuscle (36298105211).jpg|Pacinian corpuscle.
</gallery>

===Stains===
Myelin stain: 
*Blue = myelin.

Gomori trichrome: 
*Axon = green.
*Myelin = red.

Toluidine blue staion:
*Plastic embedded semithin sections (1µm).

===Artifacts===
*Myelin splits: stretching.
*Neurokeratin: Formalin fixation (longitudinal: "herringbone", cross section: "wagon-wheels").
*Dark staining myelin: crushing.
*Pale expanding myelin sheets: delayed fixation.
*Uneven myelin staining: osmication problems.
*Shrunken crescentic fascicles: Hyperosmolarity.

===Reactive changes===
* Traumatic [[Peripheral_nerve_sheath_tumours#Traumatic_neuroma|Neuroma]]
* Pacinian [[Neuroma]]
* Nerve cysts.
* Neuritis ossificans.
* Localized interdigital neuritis ([[Morton neuroma]]).

===Degenerative changes===
Types:<ref>URL: [http://missinglink.ucsf.edu/lm/ids_104_musclenerve_path/student_musclenerve/nervepath.html http://missinglink.ucsf.edu/lm/ids_104_musclenerve_path/student_musclenerve/nervepath.html]. Accessed on: 9 November 2010.</ref>
*Axonal degeneration.
*Wallerian degeneration. 
*Segmental demyelination. 

====Axonal degeneration====
*Axonal swelling.
*Intra-axonal filamentous aggregates.
*Mitochondrial abnormalities.
*Aggregation of organelles and dense bodies.

====Wallerian degeneration====
*Watery axon and granular disintegration (distal).
*Macrophage accumulation (3-4d after transsection). 
*Many lysosomes (CD68+ve). 
*Endoneurial proliferation.
*Digestion chambers - '''key feature'''.

Images: 
*[http://missinglink.ucsf.edu/lm/ids_104_musclenerve_path/student_musclenerve/subpages/digchamb1.html Digestion chambers (missinglink.ucsf.edu)].
*[http://commons.wikimedia.org/wiki/File:Digestion_chambers_--_very_high_mag_-_cropped.jpg Digestion chambers (WC)].

====Segmental demyelination====
*Onion bulb formations - '''key feature'''.
<gallery>
File:Onion bulbs semi thin nerve biopsy.jpg | Onion bulbs in toluidine blue stain.
File:Onion bulb formation HMSN.jpg | Onion bulbs in HSMN type I.
</gallery>

===Regeneration===
*Axon sprouts (regenerating clusters): Three or more closely apposed myelinated axons. 
*Thin myelin sheaths.

===Inflammation===
*[[Inflammatory pseudotumour]].
*[[Leprosy]] (Leprous neuropathy).
*[[Sarcoidosis]].
*CMV neuritis in immuncompromised patients.
*[[Vasculitis]].
*Paraprotein-associated neuropathy.
*Neuropathy with macrophage-induced demyelination (CIDP, GBS).

====Guillain–Barré syndrome====
*Acute inflammatory demyelinating polyneuropathy (AIDP)
*Preceding infection (RSV, EBV, CMV, HIV, Mycoplasma).
*Monophasic course of motor / sensory deficits.
*Hours to 4 weeks.
*Elevated CSF protein but normal cell count.
*Mononuclear ednoneurial perivascular inflammatory infiltrate (mostly CD4+ve).
*Destructive myelin stripping by macrophages.
*Reduced fiber density.
*Uncompacted myelin / Widely spaced myelin.

====Chronic inflammatory demyelinating polyneuropathy (CIDP)====
*Progredient course longer than 8 weeks.<ref>URL: [http://path.upmc.edu/cases/case426.html http://path.upmc.edu/cases/case426.html]. Accessed on: 14 
November 2010.</ref>
*Progressive or relapsing and remitting course.
*Multifocal affections of proximal nerves (motor and sensory symptoms).
*Responsive to steroids.
*Enlargement of affected nerve.
*Variation of fiber density between fascicles / reduced axon numbers.
*CD4+ve/CD8+ve inflammatory infiltrates(approx. 65% cases).
*Demyelination (thinly myelinated axons, macrophages).
*Onion-bulb formations (15-40%, chronic recurrent demyelination and remyelination).
DDx: Familial hypertrophic neuropathy.

====Neurosarcoidosis====
*Neurological symptoms in 5% of sarcoidosis cases.
*Granulomas may be endoneurial or epineurial.
*Compact mass of epitheloid cells.
*Perilesional fibrosis and lymphocytic infiltrates.
*Axonal loss and regenerating fibers.
*Segmental demyelination and remyelination.

====Vasculitic neuropathy====
*Endoneurial and epineurial mircrovessels, arterioles and venules.
*Ischemia of nerve: thrombosis and fibrinoid necrosis.
*Signs of previous vasculitis: Vessel narrowing, fragmentation of elastica, fibrous obliteration and recanalization.
*Often nerve involvement in systemic vasculitis:
**Medium-sized epineurial vessels: mostly classic polyarteritis nodosa.
**Small and medium-sized vessels and eosinophilia: Churg-Strauss angitis.
**Small vessels and necrotizing: ANCA-associated microscopic polyangitis.


<gallery>
File:Leprosy with perineural invasion 3.jpg | leprosy with perineural invasion. H&E stain (WC/Kozhikode)
File:Granulomatous_nerve_inflammation.jpg | Granulomatous inflammation of peripheral nerve in sarcoidosis (WC/jensflorian)
</gallery>

===Other Diseases===
*Amyloid neuropathy: Amorphic endoneurial deposits.
**TTR amyloidosis is of specific interest, because treatment options exist.<ref>{{Cite journal  | last1 = Adams | first1 = D. | last2 = Koike | first2 = H. | last3 = Slama | first3 = M. | last4 = Coelho | first4 = T. | title = Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease. | journal = Nat Rev Neurol | volume = 15 | issue = 7 | pages = 387-404 | month = Jul | year = 2019 | doi = 10.1038/s41582-019-0210-4 | PMID = 31209302 }}</ref>
**Example of amyloid deposits [https://www.nature.com/articles/s41582-019-0210-4/figures/3 here]
*Neuropathy associated with paraproteinemia: Alterations in myelin periodicity, nerve fiber loss.
**[[MGUS]] - Monoclonal gammopathy of unknown significance.
** Multiple myeloma.
**[[POEMS]] syndrome.
**[[LCDD]] - light chain deposition diesease.
*Toxic polyneuropathy (drug toxicity).<ref>URL: [http://path.upmc.edu/cases/case173.html http://path.upmc.edu/cases/case173.html]. Accessed on: 8 January 2012.</ref>
*Polyglucosan body disease.

===Neoplasms===

''Main article: [[Peripheral nerve sheath tumours]]''

*Nerve sheath tumors:
**[[Schwannoma]]
**[[Neurofibroma]]
**[[Perineurioma]]
**[[Nerve sheath myxoma]]
**[[Malignant peripheral nerve sheath tumour]]
*Non neurogenic-tumors of the nerve:
**[[Paraganglioma]]
**[[Lipoma]]
**[[Hemangioblastoma]] <ref>{{Cite journal  | last1 = Gläsker | first1 = S. | last2 = Berlis | first2 = A. | last3 = Pagenstecher | first3 = A. | last4 = Vougioukas | first4 = VI. | last5 = Van Velthoven | first5 = V. | title = Characterization of hemangioblastomas of spinal nerves. | journal = Neurosurgery | volume = 56 | issue = 3 | pages = 503-9; discussion 503-9 | month = Mar | year = 2005 | doi =  | PMID = 15730575 }}</ref>
**[[Synovial sarcoma]] <ref>{{Cite journal  | last1 = Scheithauer | first1 = BW. | last2 = Amrami | first2 = KK. | last3 = Folpe | first3 = AL. | last4 = Silva | first4 = AI. | last5 = Edgar | first5 = MA. | last6 = Woodruff | first6 = JM. | last7 = Levi | first7 = AD. | last8 = Spinner | first8 = RJ. | title = Synovial sarcoma of nerve. | journal = Hum Pathol | volume = 42 | issue = 4 | pages = 568-77 | month = Apr | year = 2011 | doi = 10.1016/j.humpath.2010.08.019 | PMID = 21295819 }}</ref>

=See also=
*[[Neuropathology]].

=References=
{{reflist|2}}

=External links=
*[http://moon.ouhsc.edu/kfung/jty1/NeuroHelp/ZNEWWU10.htm How to work up a muscle biopsy (ouhsc.edu)].
*[http://neuromuscular.wustl.edu/lab/mbiopsy.htm Muscle biopsies (wustl.edu)].

[[Category:Neuropathology]]