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Flashcards in Neuromuscular Pathology + Pictures Deck (29)

Describe the difference between Segmental demyelination and axonal degeneration? 

Segmental Demyelination -- see no myelin between 2 nodes of Ranvier but axon continues anyways


Axonal degeneration - see only Myelin blebs / ovaloids/spheroids where axon used to be (can eventually lose myelin sheath secondarily) 


What is a Traumatic Neuroma? 

After a trauma/severing of nerve, proximal elements grow out and proliferate to make new connections 


Get CT and scarring and growth and creates a little bump


Ex. Amputation neuroma and often associated with phantom limb pain


What is the classic appearance of chronic demyelination? 

Onion Bulbing


Schwann cell proliferation in response to repetitive loss of myeling and see multiple segments of swhann cell wrapping around 


What are the inflammatory demyelinating neuropathies? 

Guillain-Barre Syndrome  can cause either: 

Acute Inflammatory Demyelinating Polyradiculoneuropathy (acute onset, T cell attack myelin with Ascending paralysis)

Chronic Inflammatory Demyelinating Polyradic (CIDP) (chronic demyelination - onion bulbs)



Diphtheria Toxin is Demyelinating


What are other causes of infectious neuropathy? 

Leprosy --> Axonal destruction and demyelination from Mycobacterium Leprae


Diphteria - demyelination


VZV - Axonal destruction as it attacks DRG


What are the Hereditary Neuropathies discussed here? 

Hereditary Motor and Sensory Neuropathy Type 1 (Charcot Marie Tooth Disease) and Familial Amyloid Neuropathy 


What is Charcot Marie Tooth Disease and how does it present? What can yo usee with it? Genetics?

Type 1 Motor and sensory neuropathy from 17p11.2 Duplication including PMP22 

Autosomal Dominant 


Chromic demyelination leading to ONION BULBING as nerves enlarge from Schwann CEll Proliferation 


What is Familial Amyloid Neuroathy? How does it compare to Acquired amyloid neuropathy? 

Familial - build up of Transthyretin deposits in nerves


Acquired - deposits of Light Chain amyloid (from plasma cell dyscrasia or MGUS) 


Both cause axonal degeneration and more small fiber neuropathy 


What is Vasculitic Neuropathy? How does it present? 

can be Mononeuritis Multiplex: random peripheral nerve palsy in different partys 

Can be Polyarteritis Nodosa 

Either way see Marked, sub-acute destruction of axons and an ischemic-like process leading to axon destruction bc necrotixing destruction of BV 


What are the differences between type 1 and type 2 muscle fibers? 


- red myoglobin, Slow twitch and sustained action, high Oxidative enzymes - aerobic, lots of mitochondria and lipids

Marathon muscles

Type 2: Opposite

-white, fast twitch for sudden action, low oxidative enzymes, anaerobic, few mitochondria, less lipid, susceptive to disuse



Which fibers are more likely to atrophy from deconditioning disuse? 

Type 2 (stain dark with ATPase stain pH 9.4) 


How is muscle fiber type determined? what happens if denervation? 

Muscle Fiber type determined by pattern of stimulation from Anterior Horn nerve cells


Acute Denervation and atrophy of affected fibers --> Collateral sprouting and Fiber Type Grouping as get re-innervation of area --> subsequent denervation with grouped atrophy 


When do you see Fiber type Grouping? 

Disease of NERVE not muscle!!!

denervation and then subsequent renervation of muscle


What are the basic patterns associated with etiologies of myopathy? 

Dystrophic - increased CT replacement of muscle

Metabolic - increases Mitochondria, glycogen, lipid

Toxic - necrotizing

Congential - variable

Inflammatory - inflammation but either is or is not responsive to steroids!!! 


In general, what happens in muscular dystrophy? 

Genetic disease where you have a mutation in the Dystrophin Axis which is the cytoskeleton of muscle between the Actin and the Muscle Cell membrane


Mutations in these proteins and get compromised integrity of muscle as it contracts 




What do you classically see in Muscular Dystrophy? 

Endomysial Fibrosis!!!!!

Muscle fiers necrose and drop out and are not replaced by anything but collagen 


can get fibro-fatty ingrowth of muscles which in Duchenne's Disease is pseudohypertrophy 

Shown here - increased fibrosis and collagen and a lot of Small fibers and 1 big hypercontracte done too 


What are the 2 different Dystropinopathy phenotypes? 

Duchenne Phenotype - severe; childhood onset muscular dystrophy - most common and most severe

- see complete loss of dystrophin band on western blot 


Becker Phenotype - milder X-linked disease seen mostly in boys 

- see partial loss (weaker) or truncated dystrophin band on western blot 


Wht is Limb-Girdle Syndrome? 

Mutations in various proteins around the dystrophin axis 


get PROXIMAL distribution of weakness 


What is Myotonic Dystrophy and what are the two types? 


What do you see on histology? 

DM1 = Trinucleotide repeat disorder with anticipation of age ofonset and phenotype in 19qCTG repeat


DM2 = 3qCCTG tetranucleotide repeat 


Muscle Histology shows non-specific changes




What are the metabolic Myopathies? what presentations do you see? 

Disorders of Energy metabolism and so get Cramping, exercise intolerance and infanile onset that can be severe/fatal


Mitocondrial Diseases or Glycogen STorage Diseases 


What pathology do you see with Metabolic Myopathies? 

RAGGED RED FIBERS on Gomori's Trichrome stain - increased proliferaction of mitochondria bc energy deficit (see picture) 


Paracrystalline "Parking Lot" Mitochondrial Inclusions


Or Cellular accumulations of glycogen if a Glycogen Storage Disease  


What are toxic myopathies? What causes them? What is the Pathology? 

Toxic myopathies, often caused with Statins or Ethanol, cause painful necrosis of muscle fibers


see Fiber necrosis WITHOUT lymphocytic inflammation 

Necrotizing myopathy without lymphyocyte infiltrates (just myophagocytosis of necrotic muscle fiber) 




What are the congenital myopathies? What do you see with those? 

PResent at birth, althought no always evident, these are named after their pathologic finding


Nemaline Myopaty - little rods on stain, expansion of Z disk material


Central Core Disease- RYR1 ryanodine receptor mutation 


What is central core disease? What's unique about it? What's the pathology? 

Central Core disease is a congenital myopathy with variable age of onset - can manifest in adulthood

Pts have mutation of RYR1 Ryanodine Receptor Gene and are Susceptible to Malignant Hyperthermia with General Anesthesia!!!!!!!


On Pathology - see NADH stains shows Type 1 fibers with decreased reactivity in the center (central cores = absence of oxidative stainig) 





What is the general presentation for inflammatory myopathies? What are the inflammatory myopathies? 

Generally present with pain, muscle weakness, and elevated CPK (but not always) 


They are Polyomyositis, Dermatomyositis, and Inclusion Body Disease 


Polyomyositis: Presentation, Mechanism, Pathology 

Presentation: muscle pain, weakness, ELEVATED CPK, more common in women

Mechanism: Cytotoxic CD8 T cell mediated autoimmune myopathy

Pathology: Endomysial inflammation and lymphocytic involvement of non-necrotic muscle fibers, chronic inflammation, eventual fiber necrosis 

can see fiber regeneration and acute fiber necrosis 



Dermatomyositis: PResentation, Mechanism, and PAthology 

Presentation: Heliotrope rash, weakness, modestly elevated CPK, Middle-aged women or in childhood 


Mechanism: CD4 mediated Autoimmune Vasculiutis/Myopathy

Pathology: Perivascular and Perymysial Inflammation - Perifascicular Atrophy

Infalmmation in periphery and more atrophic than in center

(see picture) 


Inclusion Body Myositis: Presentation, Mechanism, Pathology 

Presentation: Distal WEakness!!!!! finger tips and knees  Atrophy, CPK may be normal; tends to be Older Men, progressive, chronic smoldering distal weakness


Mechanism: Degenerative myopathy with CD8 T cells

Pathology: Chronic Inflammation and atrophy, Rimmed Vacuoles with accumulations of various proteins, Endomysial Chronic Inflammation, Can see Filamentous Amyloid-like inclusions (or tau, or ubiquitin, or TDP-43 etc 


See picutre