Peripheral Nerve and Skeletal Muscle Pathology Flashcards
1
Q
Guillain-Barre Syndrome (acute inflammatory demyelinating polyneuropathy)
A
- life threatening resp paralysis
- weakness beginning in distal limbs that rapidly advanes to affect prox muscle function
- Inflammation and demyelination of spinal nerve roots and peripheral nerves
2
Q
What is the pathogenesis of guillain-barre thought to be?
A
-an acute onset immune mediated demyelinating neuropathy
3
Q
What precedes guillain-barre syndrome?
A
-an acute, influenza-like illness
4
Q
What is the most prominent lesion in guillain barre?
A
-segmental demyelination affecting peripheral nerves is the most prominent lesion
5
Q
clinical features of guillain barre?
A
- ascending paralysis and areflexia
- CSF ptn levels are elevated
6
Q
tx for guilain barre
A
-plasmapheresis and IV immunoglobulin appear to be beneficial
7
Q
Chronic Inflammatory Demyelinating poly(radiculo)neuropathy
A
-mot common chronic acquired inflammatory peripheral neuropathy, charcterized by symmetrical mixed sensorimotor polyneuropathy that persists for 2 months or more
8
Q
Neuropathy associated with systemic autoimmune diseases
A
- RA
- SLE
- Sjogren
9
Q
Lepromatous Leprosy
A
- schwann cells are invaded by mycobacterium leprae
- loss of sensation contributes to injury
- thus, large traumatic ulcers may develop
10
Q
Tuberculoid leprosy
A
- active cell mediated immune response to M leprae
- dermal nodules containing granulomatous inflammation
11
Q
lyme disease
A
- polyradiculopathy
- unilateral or bilateral facial nerve palsies
12
Q
HIV/AIDS
A
-later stages are associated with a distal sensory neuropathy that is often painful
13
Q
Diphtheria
A
-developing world
-peripheral nerve dysfunction results from the effects of diphtheria exotoxin
-
14
Q
Varicella-Zoster Virus
A
- one of the most common viral infections of peripheral nervous system
- latent infection persists within neurons of sensory ganglia
- gets transported along the sensory nerves to the skin
- there, it infects keratinocytes, leading to a painful, vesicular skin eruption (shingles) in a distribution that follows sensory dermatomes
15
Q
What is the most common cause of peripheral neuropathy?
A
- diabetes
- ascending distal symmetric
16
Q
Uremic neuropathy
A
- renal failure
- axonal degeneration
- regeneration and recovery are common after dialysis
17
Q
What is the most notorious cause of toxic neuropathies?
A
-chemotherapeutic agents
18
Q
POEMS syndrome
A
- polyneuropathy
- organomegaly
- endocrinopathy
- monoclonal gammopathy
- skin changes
19
Q
Hereditary motor and sensory neuropathies/Charcot Marie tooth disease (CMT)
A
- most common inherited peripheral neuropathy
- schwann cell hyperplasia and onion bulb formation
20
Q
What chromosome is duplicated in CMT1A?
A
- 17
- PMP22
- 2nd decade of life
- slowly progressive distal demyelinating motor and sensory nueropathy
21
Q
CMT1B
A
-caused by mutation in the myelin protein zero gene and accounts for about 9% of genetically
22
Q
What kind of injury is found in CMT2?
A
-axonal rather than demyelinating injury
23
Q
Hereditary neuropathy with pressure palsy
A
- deletion of gene encoding PMP22
- transient motor and sensory mononeruopathies that are triggered by compression of individual nerves at sites that are prone to entrapment
24
Q
What is the characteristic morphologic feature for hereditary neuropathy with pressure palsy?
A
-swolen, bulbous myelin sheaths at the end of internodes (tomaculi)
25
Familial amyloid polyneuropathies
- characterized by amyloid deposition within peripheral nerves
- mutation of the the transthyretin gene
26
How do diseases of the NM junction present?
-with painless weakness
27
Myasthenia gravis
Autoantibodies against the postsynaptic Ach receptor at the NM junction
- more commonly seen in women
- competitive inhibition
- bimodal age distribution
28
what else will there be in a mysthenia gravis patient?
- thymic abnormalities
| - thymectomy improves sx
29
clinical features of mysathenia gravis
- that worsens with use and IMPROVES WITH REST
- classically involves the eyes, leading to ptosis and diplopia
- sx improve with anticholinesterase agents
30
Lambert-Eaton myasthenic syndrome
- antibodies against presynaptic Ca2+ channels of the nm junction
- arises as a paraneoplastic syndrome, most commonly due to SMALL CELL CARCINOMA OF THE LUNG
- leads to impaired Ach release
31
what is required for Ach release?
-firing of presynaptic calcium channels
32
Clinical features of lambert-eaton syndrome
- pros muscle weakness that IMPROVES WITH USE
- eyes are usually spared
- Ach agents do not improve symptoms.. makes sense bc Ach isn't the issue
- resolves with resection of the cancer
33
tx for lambert eaton
-drugs that increase AcH rlease by depolarizing synaptic membranes
34
What mutation will be there is congenital myasthenic syndromes?
-most commonly LOF in the gene encoding the e subunit of the AcH receptor
35
Botulinism
- C botulinum
| - blocking the release of Ach from presynaptic neurons
36
what is a common name for muscle relaxants that block AcH receptors, resulting in flaccid paralysis?
- Curare
| - used as poison on arrow tips
37
Dermatomyositis
- Inflammatory disorder of the skin and skeletal muscle
| - unknown etiology
38
clinical features of dermatomyositis
- bilateral prox muscle weakness; distal involvement can develop late in disease
- rash of upper eyelids (heliotrope rash); malar rash may also be seen
- red papules on elbows, knuckles, and knees (gottron papules)
39
lab findings for dermatomyositis
- increased creatine kinase
- positive ANA and anti-Jo-1-antibody
- perimysial inflammation with perifascicular atrophy on biopsy
40
tx for dermatomyositis
-steroids
41
What other antibodies besides anti-Jo-1 antibodies would we find in dermatomyositis?
- anti Mi2 antibodies: prominent gottron papules and heliotrope rash
- anti-P155/P140 antibodies: for paraneoplastic and juvenile cases
- anti Jo-1 will have interstitial lung disease and "mechanics hands"
42
What is the key morphologic feature of dermatomyositis?
- perfascicular atrophy... characteristic of dermatomyositis
| - polymyositis is endomysial
43
What is the most common inflammatory myopathy in children?
-dermatomyositis
44
Polymyositis
- inflammatory disorder of skeletal muscle
- resembles dermatomyositis clinically, but skin is NOT involved
- endomysial inflammation (CD8+ T cells) with necrotic muscle fibers is seen on biopsy
- adult onset
- symmetric proximal muscle involvement
45
What is believed to play a major role in dermatomyositis but not polymyositis?
-vascular injury
46
Inclusion body myositis
- late adulthood
- most common inflammatory myopathy in pts older than 65
- quadriceps and distal upper extremity muscle weakness
- most myositis associated autoantibodies are absent
- anti cN1A
- doesnt' respond to steroids
47
What are the leading culprits of toxic myopathies?
- statins
| - myopathy is the most common complication of statins
48
X-linked muscular dystrophy
- degeneative disorder characterized by muscle wasting and replacement of skeleatl muscel by adipose tissue
- due to defects in dystrophin gene
49
what is dystrophin important for?
-anchoring the muscle cytoskeleton to the ECM
50
Duchenne muscular dystrophy
- due to deletion of dystrophin
- presents as prox muscle weakness at 1 year of age, progresses to involve distal muscles
- calf pseudohypertrophy is characteristic
- serum creatine kinase is elevated
51
What does death result from in Duchenne?
- cardiac or respiratory failure
| - the myocardium is commonly involved
52
Becker muscular dystrophy
- due to mutated dystrophin
- clinically results in milder disease
- so, it's not totally deleted
53
where is the dystrophin gene?
-on the X chromosome
54
what will we see on IF for Duchenne and Becker
- Duchenne: absence of normal sarcolemmal staining pattern
| - Becker: reduced staining
55
clinical presentation for duchenne?
- clumbsy boys who can't keep up with their peers
| - beckerpresents in later childhood
56
Myotonic dystrophy
-auto dominant multisystem disorder associated with skeletal muscle weakness, cataracts, endocrinopathy, and cardiomyopathy
57
pathogenesis of myotonic dystrophy
-expansions of CTG triplets in region of DMPK gene
58
Emery-Dreifuss Muscular dystropy
- caused by mutation sin genes that encode nuclear laminal proteins
- triad of slowly progressive humeroperoneal weakness, cardiomyopathy associated with conduction defects, and early contractures of the achilles tendon, spine, and elbows
- inner face of nuclear membrane
59
Fascioscapulohumeral dystrophy
- characteristic pattern of muscle inovlvement that includes prominent weakness of facial muscles and muscles of the shoulder girdle
- DUX4 overexpression on chrom 4
60
Limb-Girdle muscular dystrophy
-characterized by muscle weakness that preferentially involves proximal muscle groups
61
Carnitine palmitoyltransferase 2 deficiency
- most common disorder of lipid metabolism to cause episodic muscle damage with exercise or fasting
- impaired transport of free fatty acids into mitochondria
62
Myophosphorylase deficiency (McArdle disease)
- common glycogen storage disease
| - episodic muscle damage with exercise
63
acid maltase deficiency
- impaired lysosomal conversion of glycogen to glucose
- glycogen accumulates within lysosomes
- severe form results in generalized glyogenosis of infancy... Pompe disease
64
mitochondrial myopathies
- impair the ability of mitochondria to generate ATP
- involvement of extraocular eye muscles in common ... good clue for dx
- chronic progressive external opthalmoplegia is a common feature
- "ragged red fibers": abnormal aggregates of mitochondria
65
Spinal muscular atrophy mutation?
- auto recessive
| - LOF in SMN1 gene
66
Schwannomas
- benign tumors that exhibit schwann cell differentiation and often arise directly from peripheral nerves
- component of NF2
- chromosom 22: merlin on the NGS gene
- immunoreactivity for S-100
67
What are Verocay bodies?
- in schwannomas
| - nuclear free zones that lie between the regions of nuclear palisading
68
Neurofibromas
- benign nere sheath tumors that are more heterogenous in composition than schwannomas
- only the schwann cells in this disease show complete los of NF1 gene product
- bland Schwann cells admixed with stromal cells such as mast cells, perineurial cells, CD34+ spindle cells, and fibroblasts
69
what is the NF1 gene product?
- neurofibromin
| - suppresses RAS activity by stimulating GTPase
70
Malignant peripheral nerve sheath tumors (MPNSTs)
- high grade tumors
- arise in NF1 (1/2 of them do)
- pporly defined tumor masses that frequently infiltrate along the axis of the parent nerve and ivade adjacent soft tissues
- divergent differentiation
71
Which MPNST has rhabdomyoblastic morphology?
-Triton tumor
72
Neurofibromatosis 1
- pigmented nodules of the irs
- cutaneous hyperpigmented macules (cafe au laits pots
- LOF in NF1 on chrom 17: encodes neurofibromin
- In the absence of NF-1, RAS remains trapped in its active state
- auto dominant
73
Neurofibromatosis 2
- auto dominant
- bilateral 8th nerve schwannomas
- multiple meningioma
- much less common that NF1
- NF2 gene product: merlin
74
What are the 3 kinds of neurofibromas
- Superficial cutaneous neurofibromas: pedunculated nodules...if multiple.. NF1
- Diffuse neurofibromas: large plaquelike elevation of skin... NF1
- Plexiform neurofibromas: NF1 associated... bag of worms
75
Where do most schwannomas occur?
- at the CPA, where they are attached to the vestibular branch of the 8th nerve
- that is where the tinnitus and hearing loss come from
- "acoustic neuroma": not from 8ht nerve.... not a neuroma.... idiots
