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?
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
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?
Type 1: ONE SLOW FAT RED OX
- red myoglobin, Slow twitch and sustained action, high Oxidative enzymes - aerobic, lots of mitochondria and lipids
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?
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
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
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