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MSK II - Exam 1 > Peripheral Nerves and Skeletal Muscles Pathology (Hertz) - MT > Flashcards

Peripheral Nerves and Skeletal Muscles Pathology (Hertz) - MT Flashcards

1
Q

Nerve conduction studies measure what?

A

Velocity of conductino of the nerve, dependent on Myelin component

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2
Q

Nerve biopsies usually are taken from what nerve?

A

sural nerve

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3
Q

CSF analysis measures what 3 things in the fluid?

A

white cells, protein, glucose

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4
Q

Serum chemistry for muscle pathology is?

A

CPK

serum creatinine phosphate kinase

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5
Q
  1. Where is this disease process located?
  2. What is the process called that leads to the appearance of this leg?
A
  1. Disease process located at anterior horn in the cord
  2. Denervation atrophy
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6
Q

What does Pic A and Pic B in this EM show?

x2

A

pic A shows loosening of myelin layer in degenerating axon lower left. Normal axon upper right

pic B shows vacuoles of lipids derived from degenerating myelin

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7
Q

You are seeing a patient who reports having an influenza like illness a month ago, but has since recovered. However, he also reports burning himself on the stove top by accident while cooking and says “ I didn’t feel the pain, I only pulled my hand away when I smelled my skin burning”. He now presents with ascending paralysis and areflexia.

  1. What mechanism most likely mediated the neuropathy found in this patient?
  2. What are 5 significant epidemiologic associations with this pathology (4 infections + 1 other)?
A
  1. Immune mediated demyelinating neuropathy
  2. Campylobacter jejuni, CMV, EBV, Mycoplasma pneumoniae infections

and prior vaccination all have significant association with Guillain barre syndrome

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8
Q

What are the black dots in this nerve biopsy?

What do they cause?

A

Single black dots are lymphocytes

demyelination in Guillain barre syndrome.

Chronic inflammation

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9
Q

You are trying to diagnose a patient’s suspected guillain barre syndrome.

What study would you order besides a CSF analysis?

What would it show you?

Why would it show you this?

A
  1. Nerve conduction study
  2. decreased conduction velocity
  3. multifocal destruction of myelin segments in many axons within a nerve
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10
Q

What would be elevated in a CSF analysis in guillain barre syndrome?

why (x2)?

A
  • protein levels elevated
  • d/t inflammation and altered permeability of microcirculation within spinal roots as they traverse the subarachnoid space
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11
Q

On physical exam, what normal function dissapears rather early on in a patient afflicted with Guillain Barre syndrome?

A

Deep tendon reflexes

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12
Q

The most common chronic acquired inflammatory peripheral neuropathy is?

A

Chronic inflammatory demyelinating poly radiculo neuropathy

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13
Q

This images indicates what histologic feature?

A

Onion bulb neuropathy in figure B and a normal axon in figure A

found in chronic inflammatory demyelinating polyradiculoneuropathy

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14
Q

Chronic inflammatory demyelinating polyradiculoneuropathy is characterized by what kind of neuropathy that persists more than 2 months?

A

symmetrical mixed sensrimotor polyneuropathy

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15
Q

Neuropathies associated w/ systemic autoimmune diseases can be caused by what diseases x3?

A
  • Rheumatoid arthritis
  • Sjogren syndrome
  • Systemic lupus erythematosus
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16
Q

Neuropathy caused by SLE is of what type?

Peripheral/Central

Distal/Proximal

Sensory/Motor

A

peripheral

distal sensory

sensorimotor

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17
Q

Peripheral nerve damage can be caused by what blood vessel pathology?

A

Vasculitis

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18
Q

infectious neuropathies can arise from what diseases? x5

A
  • Leprosy (hansen disease)
  • HIV/AIDS
  • Diphtheria
  • Lyme disease
  • Varicella zoster virus
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19
Q

What causes this lesion?

A

Tick bite that causes lyme disease

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20
Q

What causes this?

A

Diphtheria

(pseudomembrane)

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21
Q

Histology would show granulomatous patterning if these papules were biopsied. What causes them?

A

Leprosy (hansen disease)

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22
Q

What is the most common cause of peripheral neuropathy?

A

Diabetes

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23
Q

This is an EM from a diabetic patient with peripheral neuropathy. What does it show?

A

Loss of myelinated fibers, a thinly myelinated fiber.

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24
Q

A patient presents with increasing loss of balance, loss of pain sensation, HemA1C >10, and also chronic skin ulcers. He wants you to prescribe a medication that helps him get an erection.

What disease does this patient have and why does he want this medication?

A

Diabetes mellitus

Diabetic neuropathy can affect the autonomic nervous system

It affects about 30% of individuals with DM

almost always in conjunction to distal sensorimotor neuropathy.

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25
Q

diabetic autonomic neuropathy can present with protean sx like? x3

A
  1. postural hypotension
  2. incomplete bladder emptying
  3. sexual disfunction
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26
Q

What are some metabolic, hormonal, and nutritional causes of neuropathies besides the diabetic neuropathy? x4

A
  1. Uremic neuropathy
  2. Thyroid dysfunction
  3. Vitamin B12 deficiency
  4. Deficiency of Vitamin B1 thiamine, and vitamine B6 pyridoxine, folate, vit E, copper, zinc
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27
Q

This man is sweating salt.

Why?

What is the result of the distal symetric neuropathy?

A
  • He is in renal failure
  • muscle cramps, distal dysesthesias, diminished DTR
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28
Q

Question on picture

A

vit B1 thiamine deficiency

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29
Q

Toxic neuropathy can arise from exposure to industrial or environmental chemicals, bio toxins, or therapuetic drugs. What are 3 general categories of things that this includes?

A
  1. alcohol
  2. heavy metals
  3. organic solvents
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30
Q

Paraneoplastic neuropathies are commonly associated with which type of cancer?

A

small cell lung cancer

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31
Q

paraneoplastic neuropathy most commonly affects motor or sensory function?

A

both, sensorimotor neuropathy

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32
Q

cancer may commonly cause mononeuropathy d/t direct infiltration or…..

A

compression

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33
Q

Neoplastic B cells may cause demyelination leading to peripheral neuropaty because they can…..

A

Secrete monoclonal Immunoglobulins or paraproteins that damage nerve. Specifically IgM antibodies

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34
Q

What does this histo slide show?

What type of neuropathy does this cause?

A

small cell lung cancer

Paraneoplastic neuropathy

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35
Q

inherited peripheral neuropaties usually present in what patient population?

A

adults

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36
Q

Inherited mixed sensory and motor neuropathies are known as?

A

Charcot marie tooth (CMT) disease

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37
Q

CMT disease is byfar the most common inherited peripheral neropathy. This disease is characterized by what distal limb PE signs/symptoms (x3)?

A
  1. distal muscle atrophy (perineal atrophy)
  2. sensory loss
  3. foot deformities (pes cavus)
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38
Q

A person with this feature could also have what other finding on PE d/t loss of sensory function?

A

ulcers on feet and hands d/t loss of sensory function

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39
Q

This is a congo red stain of a nerve biopsy.

What is the pink?

What does it cause in nerves?

A
  • amyloid
  • Familial amyloid polyneuropathy
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40
Q

Diseases that impair the NMJ usually present with what cardinal sx?

A

painless weakness

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41
Q

The most common cause of NMJ protein inhibition leading to disruption of neuromuscular transmission is?

A

Autoantibodies

(like the ones found in myasthenia gravis)

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42
Q

Autoantibodies in Myasthenia gravis target what structure?

A

ACh receptors on the post synaptic motor end plate

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43
Q

In the presence of anti ACh receptor autoantibodies, what other pathology should you look for due to its high association with the latter?

A

Thymic abnormalities

44
Q

10% of pathients with myasthenia gravis have this. What is it?

An additional 30% have a different abnormality of the same organ called?

A
  • thymoma, a tumor of thymic epith cells
  • thymic hyperplasia
45
Q

A patient presents with fluctuating muscle weakness with exertion, diplopia, and ptosis.

You suspect what disease?

Diagnosis of this disease is based on what lab findings? x2

A
  • Myasthenia Gravis
  • Identification of autoantibodies
  • electorphysiologic studies revealing a decrement in muscle response w/ repeated stim
46
Q

First line treatment agents for Myasthenia gravis are?

A

AChase inhibitors like Neostigmine, pyridostigmine, ambenonium (doesn’t cross BBB)

47
Q

Dr. Linger integration question:

D/t the bradycardia / bronchospasm ADR risk associated with the edrophonium test to diagnose myasthenia gravis, another test was developed to diagnose.

What is this test?

How does it work?

A
  • Ice pack on eyelid test for 2-3 min
  • ice temporarily inhibits AChase enzyme activity, thus relieving ptosis
48
Q

A patient presents with complaints of muscle weakness in the extremities, which improves in strength with repetitive stimulation.

  • What disease is this?
  • You test for antibodies that do what?
  • You also check for what associated pathology, since about half the cases have it.
A
  1. Lambert eaton myasthenic syndrome
  2. antibodies block acetylcholine release by inhibiting presynaptic Ca2+ channels
  3. Neuroendocrine carcinoma of the lung
49
Q

Describe the cells you would find in the mass identified in this CT

A

small cells with big nuclei, and little to no cytoplasm

indicative of small cell carcinoma of da lung (oat cell carcinoma of the lung)

50
Q

Match Myasthenia gravis and Lamber eaton myastenic syndrome to their respective figures in the pic

A
51
Q

A self proclaimed doomsday prepper proudly brings out some of the jarred foods he has been preserving for the coming apocalypse to feed his guests at a dinner party. Some of his guests present to the ED the next day with worsening double vision, dysphagia, dry mouth, slurred speech and muscle weakness that starts in the shoulders and descends through the body.

  • What is the organism most likely responsible for these sx?
  • What gram properties and oxygen use status characterizes this organism?
  • How does this organism cause the sx (name the condition too)?
A
  1. Clostridium botulinum
  2. gram positive anaerobic organism
  3. Neurotoxin causing botulism
52
Q

C. botulinum produces a neurotoxin that is popularly known as botox. This toxin acts at the NMJ by…….?

  • this causes what sx? x6
A

blocking the release of ACh from presynaptic neurons

  • double & blurry vision
  • ptosis
  • slurred speech
  • dysphagia
  • dry mouth
  • muscle weakness (shoulders to all of body)
53
Q

What is a curare?

A

common name for related muscle relaxants that block ACh receptors resulting in flaccid paralysis

54
Q

This is an NADH stain of a skeletal muscle biopsy.

Why is this considered a normal looking biopsy?

A

Checker board pattern shows the even distribution of red and white muscle fibers.

55
Q

What differs a neurogenic disease from a dermatomyositis in terms of nerve and muscle fiber distribution?

A
  • clusters or groups of atrophic fibers are seen with neurogenic diseases
  • Perifascicular atrophy is seen in dermatomyositis, damage to myfibers directly.
56
Q

Neurogenic injuries lead to what occurence in regards to the organization of muscle fiber types?

What happens during the subsequent regeneration of these neuromuscular units?

A

Fiber type grouping

* same type of muscle fibers associated with a given nerve atrophy d/t denervation

* regeneration in distinct group types with loss of checkerboard patterning

57
Q

Segmental myofiber degeneration and regeneration is seen when only part of a myofiber undergoes necrosis. This degeneration is associated with release of what detectable substance into the blood?

A

Cytoplasmic enzyme known as Creatine kinase

(marker of muscle damage, CPK)

58
Q

The inflammatory myopathies we covered in this lecture are? x3

A
  • polymyositis, dermatomyositis, inclusion body myositis
59
Q

other immune mediated disorders that can cause myositis include? x4

*not as emphasized to just flip it.

A

SLE

systemic sclerosis

sarcoidosis

certain infectious agents

60
Q

Que esta pasando en la imagen?

What is happening in the picture?

A

Lymphocytic invasion of the muscle fiber indicating an inflammatory myopathy

61
Q

A patient presents with proximal muscle weakness and skin changes. In your mind, you think of an autoimmune disease which:

  • Targets what structures?
  • This leads to?
  • what disease is this?
A
  • small blood vessels
  • muscle injury
  • Dermatomyositis
62
Q
  • What antibody is associated to the heliotropic rash on this woman’s face?
  • these antibodies are directed against?
  • What does the histology pic show? x2
A
  1. Anti Mi2 antibodies
  2. directed against helicase implicated in nucleosome remodeling
  3. perifascicular atrophy of muscle fibers and inflammation
63
Q

You are looking over a patient’s chart and see a description for a rash as “mechanic’s hands”. You also see that the patient has a history of non erosive arthritis, dermatomyositis, and interstitial lung disease.

  • What antibodies do you suspect to be the cause of the above presentation?
  • what do these antibodies target?
A
  1. Anti Jo1 antibodies
  2. target enzyme histidyl t-RNA synthetase
64
Q

You are looking over a case report in which a juvenile patient had a paraneoplastic disease and was diagnosed with dermatomyositis.

  • which antibody do you suspect this child has/had
  • what is it directed against?
A
  1. anti P155/P140
  2. against transcriptional regulators
65
Q

A patient you are seeing has recently been diagnosed with dermatomyositis. On his diagnostic visit, he had reported he had difficultiy rising from his chair and climbing steps.

  • Why is this?
  • If left untreated, what sx can he expect later on in the disease process?
A
  • proximal muscles are affected first
  • later on, fine movements controlled by distal muscles are affected.
66
Q

Muscle damage is gauged with what tests in a patient with dermatomyositis?

A
  • Electrophysiologic studies
  • elevation of serum creatine kinase
67
Q

What is a heliotrope rash?

What is a gottron papule?

What disease can characterized by both the above?

A
  • heliotrope rash is lilac colored discoloration of upper eyelids associated with periorbital edema.
  • Gottron papule is scaling erythematous eruption or dusky red patch over knuckles, elbows, knees
  • dermatomyositis
68
Q

A patient diagnosed with dermatomyositis reports dysphagia.

Why is this?

A
  • a third of the individuals with dermatomyositis have involvement of oropharyngeal and esophageal muscles.
69
Q

A patient died of a rapidly progressive interstitial lung disease. In her final days, she had a hard time drawing the finer details in her paintings. What type of autoantibodies likely caused her condition?

A

Anti Jo 1 antibodies

directed against enzyme histidyl tRNA synthetase

associated with interstitial lung disease, non erosive arthritis, mechanic hand rash

70
Q

What is shown on each pic?

A

A - heliotropic rash

B - mechanic hand rash

C - Gottron papules on knuckles

D - gottron papules on knees

71
Q

A 40 y/o male presents with myalgia and weakness. You check for skin changes / lesions, but find none. Serum creatine kinase levels are elevated to 10x nml level (nml is between 60- 174 IU/L).

What is your diagnosis?

A

Polymyositis

72
Q

These muscles are usually affected in what inflammatory myopathy?

What type of cells would you find in the muscle biopsy surrounding the muscle fascicles diffusely?

A
  • Polymyositis
  • Cytotoxic CD8 Tcells and Macrophages with CD68 markers
73
Q

A 69 y/o man presents with progressive and slow muscle weakness which has hindered his ability to walk up stairs and write. Serum creatine kinase is elevated. No skin rashes present.

What is your diagnosis?

A

Inclusion body myositis

most common inflammatory myopathy in patients older than 65 y/o

most severe in quads and distal upper extremities

74
Q

This is a modified gomori trichrome stain of a muscle biopsy.

What does this tell you about how this patient will respond to the standard treatment protocol for inflammatory myopathies?

A

This patient will not respond to the standard first line treatments for dermatomyositis and polymyositis which include

Corticosteroids and Immunosuppressive drugs

This histology is of an inclusion body myositis

75
Q

In addition to corticosteroid first line treatment drugs, Immunosuppressive agents are used to treat poly and dermatomyositises as 3rd line therapies.

How are the Immune suppresive drugs administered?

*name a couple

A
  • administered intravenously IVIG

*rituximab, cyclophosphamide, cyclosporine (3rd line drugs)

76
Q

You are treating a patient for hypercholesterolemia with simvastatin. What must you check in your patient? (occurs in 1.5% of statin users)

A
  • serum creatine kinase levels must be checked

*statins can cause toxic myopathy

77
Q

A patient with SLE on long term treatment presents with elevated serum creatine kinase levels. Her medication used to be an antimalarial agent.

What are two agents that she could be taking?

A
  • chloroquine
  • hydroxychloroquine
78
Q

A patient who is diagnosed with hyperthyroidism has an elevated serum creatine kinase and muscle weakness.

What is the diagnosis?

What muscles are commonly affected in his condition?

A
  • thyrotoxic myopathy
  • proximal muscle weakness as acute or chronic
79
Q

Alcohol can cause toxic myopathy.

If you really wanted to get a myopathy induced by alcohol, how would you drink your alcohol?

A

Binge drink it

80
Q

A mother brings in her infant who presents with hypotonia and “floppy infant” sign. The mother has a history of muscular dystrophy as well.

  • The most common muscular dystrophies are X-linked and stem from mutations that disrupt what?
A

disrupt function of large structural protein called Dystrophin

81
Q

Duchenne and Becker muscular dystrophies are caused by?

A

X-linked mutations that disrupt the function of dystrophin gene

82
Q

These are the stages of Ducheenne muscular dystrophy.

  • What stage of the disease is demonstrated by each picture? (early/late)
  • What are the histologic findings that demarkate each stage of the disease?
A
  • early, early, late
  • A = early younger age, fascicular muscle architecture is maintained but myofibers show variable size
  • B = early IHC stain shows complete absence of membrane associated dystrophin

*normal is big pic, absent dystrophin in lower right box

  • C = Late in disease shows pseudohypertrophy of lipid vacuoles
83
Q
  • The histologic picture shows what characteristic of duchenne muscular dystrophy?
  • The western blot gel tests for dystrophin. Which lanes lanes represent normal dystrophin levels, Duchenne dystrophin levels, and Becker dystrophin levels?
A
  • variable muscle fiber size characterizes duchenne muscular dystrophy
  • normal dystrophin far right lane, Becker is middle lane with reduced dystrophin, Duchenne is left lane and has absent dystrophin
84
Q

Boys with duchenne muscular dystrophy are normal at birth, very early motor milestones are met, but walking is often delayed. First indication of muscle weakness are clumsiness and inability to keep up with peers.

  • What muscles are initially affected and weakened?
  • Pseudohypertrophy with lipid vacuoles often also affects which muscles?
A
  • Pelvic Girdle muscles are weakened first. Then extends to shoulder girdle
  • Pseudohypertrophy affects lower leg muscles leading to enlargement and weakness in Lower limbs
85
Q

Describe serum creatine kinase levels through the course of duchenne muscular dystrophy.

A

elevated in first decade of life d/t ongoing muscle damage, falls as disease progresses and muscle mass is lost

86
Q

What does this pic show?

A

Pseudohypertrophy with lipid vacuoles distributed throughout muscle fibers

87
Q

What does this child have difficulty doing?

A

gower sign, indicating muscular dystrophy

88
Q

spinal muscular atrophy is a neuropathic disorder in which loss of ________ leads to muscle weakness and atrophy?

A

motor neurons

89
Q

differential diagnosis of n infant with hypotonia should include?

A
  • primary diseases of skeletal muscle
  • abnormalities of brain
  • neuronopathies
90
Q

WHat is the medical term used to describe the children in the pictures.

The child has _________

A

generalized hypotonia

91
Q

Why are some of the myofibers enlarged in this muscle biopsy of a child with spinal muscular atrophy?

A

Enlarged fibers are innervated myofibers that have undergone compensatory hypertrophy

92
Q

A patient who has a history of congenital myopathy needs an airway during a surgery. The anesthesiologist in charge of intubation uses vecuronium instead of succinyl choline as the anesthetic agent because….

  • he is concerned about what?
  • What are the sx of this pathology?
  • What causes these sx? (pathophys)
A
  • Malignant hyperthermia (ion channel myopathy)
  • Sx = tetany, excessive heat production, hypermetabolic state tachycardia, tachypnea, muscle spasms.
  • upon exposure to anesthetic succinyl choline, mutated Ryanodine (RYR1) receptor allows increased efflux of calcium from Sarcoplasmic reticulum leading to tetany and excess heat production
93
Q

Three common types of periheral nerve sheath tumors are schwannomas, neurofibromas, and malignant peripheral nerve sheath tumors (MPNST).

  • The vast majority of these tumors show evidence of differentiation in what cell type?
  • Peripheral nerve sheath tumors are associated with what common familial tumor syndromes? x3
A
  • Schwann cell differentiation
  • Neurofibromatosis type 1, NF type 2, and Schwannomatosis
94
Q

Schwannomas are:

  1. malignant or benign tumors?
  2. Show schwann cell differentiation and often arise directly from what?
  3. This image indicates an over production of what?
  4. The image indicates a loss of expression of what?
A
  1. benign tumors
  2. peripheral nerves
  3. over productino of myelin
  4. loss of NF2 gene product named MERLIN
95
Q
  • In picture A (top left),

what is the dense eosinophilic area known as and what is the pale area with hyalinized blood vessel known as?

  • In picture B (top right),

What are these structures and what forms them?

*- In picture C (bottom left),

Plexiform neurofibroma is pictured, what characteristic is shown?

*- In picture D (bottom right),

Plexiform neurofibroma is pictured, this shows carrot shaving patterning made of what?

A
  • pic A

dense eosinophilic area = Antoni A area

Pale area w/ hyalinized blood vessel = Antoni B area

  • pic B

antoni A area with tumor cell nuclei aligned in palisading rows leaving anuclear zones and resulting in formation of structure termed Verocay bodies

*pic C

multiple nerve fascicles are expanded by infiltrating tumor cells

*pic D

bland spindle cells are admixed with wavy collagen bundles

96
Q

This CT scan is from a man who has been diagnosed with a schwannoma and has presented to the office with facial weakness, tinnitus and hearing loss.

  • Why does this man complain of tinnitus and hearing loss?
  • Why facial weakness?
A

most schwannomas cause sx by LOCAL COMPRESSION of involved nerve or adjacent structures

  1. The Schwann cell tumor grows on the VESTIBULAR branch of the 8th nerve and can compress the nerve.
  2. The schwannoma on the 8th nerve can grow so big it compresses the facial nerve (CN VII) thus causing facial weakness
97
Q

A pathologist shows you a biopsy composed of neoplastic schwann clls mixed with perineurial like cells, fibroblasts, mast cells, and CD34+ spindle cells.

  • Is this tumor mlignant or benign?
  • What is it?
  • what are the 3 subtypes of this tumor?
A
  • benign
  • Neurofibroma = nerve sheath tumor
  • Superficial cutaneous, Diffuse, Plexiform
98
Q

You biopsy a pedunculated nodule that is NF1 associated. You correctly identify it as what type of Neurofibroma?

A

Superficial cutaneous neurofibroma

99
Q

You biopsy a mass from a large deep nerve root, which you identify as a neurofibroma. What subtype is it?

A

Plexiform neurofibroma

100
Q

you see a large plaquelike elevation of skin on a patient. Upon examination of a biopsy you took from it, you identify that it is NF1 associated and a neurofibroma. what subtype is it?

A

diffuse neurofibroma

101
Q

About half of these tumors arise in Neurofibromatosis type 1.

  • What are they?
  • They can transform into what?
A
  • plexiform neurofibromas
  • Malignant peripheral nerve sheath tumors (MPNSTs)
102
Q

This tumor contains glandular, cartilaginous, osseus, and rhabdomyoblastic morphology.

  • What is this type of tumor called?
  • What is the term that describes the formation of these focal areas?
A
  • Triton tumor (type of MPNST)
  • divergent differentiation
103
Q

You have a patient who presents with cafe au lait spots, multiple cutaneous/diffuse neurofibroas, and has a lot of plexiform neurofibromas.

  • What type of neurofibromatosis does this man have?
  • What should you be worried about?
A
  • type I
  • transformation of plexiform neurofibromas into MPNSTs
104
Q
  • This MRI shows what?
  • What disease is this?
  • What is the genetic inheritance pattern of this disease?
A
  • MRI shows b/l 8th nerve schwannomas
  • Neurofibromatosis type 2
  • autosomal dominant

* can also include multiple meningiomas

105
Q
A

MSK II - Exam 1 (6 decks)

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