Neuromuscular Pathology + Pictures

Question 1

Describe the difference between Segmental demyelination and axonal degeneration?

Answer 1

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)

Question 2

What is a Traumatic Neuroma?

Answer 2

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

Question 3

What is the classic appearance of chronic demyelination?

Answer 3

Onion Bulbing

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

Question 4

What are the inflammatory demyelinating neuropathies?

Answer 4

_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)

OR

Diphtheria Toxin is Demyelinating

Question 5

What are other causes of infectious neuropathy?

Answer 5

Leprosy –> Axonal destruction and demyelination from Mycobacterium Leprae

Diphteria - demyelination

VZV - Axonal destruction as it attacks DRG

Question 6

What are the Hereditary Neuropathies discussed here?

Answer 6

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

Question 7

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

Answer 7

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

Question 8

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

Answer 8

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

Question 9

What is Vasculitic Neuropathy? How does it present?

Answer 9

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

Question 10

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

Answer 10

Type 1: ONE SLOW FAT RED OX

• 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

BodyBuidler

Question 11

Which fibers are more likely to atrophy from deconditioning disuse?

Answer 11

Type 2 (stain dark with ATPase stain pH 9.4)

Question 12

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

Answer 12

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

Question 13

When do you see Fiber type Grouping?

Answer 13

Disease of NERVE not muscle!!!

denervation and then subsequent renervation of muscle

Question 14

What are the basic patterns associated with etiologies of myopathy?

Answer 14

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!!!

Question 15

In general, what happens in muscular dystrophy?

Answer 15

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

Question 16

What do you classically see in Muscular Dystrophy?

Answer 16

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

Question 17

What are the 2 different Dystropinopathy phenotypes?

Answer 17

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

Question 18

Wht is Limb-Girdle Syndrome?

Answer 18

Mutations in various proteins around the dystrophin axis

get PROXIMAL distribution of weakness

Question 19

What is Myotonic Dystrophy and what are the two types?

What do you see on histology?

Answer 19

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

DM2 = 3qCCTG tetranucleotide repeat

Muscle Histology shows non-specific changes

Question 20

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

Answer 20

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

Mitocondrial Diseases or Glycogen STorage Diseases

Question 21

What pathology do you see with Metabolic Myopathies?

Answer 21

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

Question 22

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

Answer 22

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)

SEE PICTURE

Question 23

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

Answer 23

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

Question 24

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

Answer 24

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)

SEE PICTURE

Question 25

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

Answer 25

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

They are Polyomyositis, Dermatomyositis, and Inclusion Body Disease

Question 26

Polyomyositis: Presentation, Mechanism, Pathology

Answer 26

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

(SEE PICTURE)

Question 27

Dermatomyositis: PResentation, Mechanism, and PAthology

Answer 27

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)

Question 28

Inclusion Body Myositis: Presentation, Mechanism, Pathology

Answer 28

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

DOES NOT RESPOND TO STEROIDS!!!!!!!!

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