Peripheral Nerve and Skeletal Muscle Flashcards
1
Q
What are the connective tissue layers of a nerve from most internal to most external?
A
- endoneurium (surrounds individual nerve fibers)
- perineurium
- epineurium (encloses entire nerve)
2
Q
What is Wallerian degeneration?
A
-when the myelin is not intact, the axons can go all different ways
3
Q
What are the two pathologic processes that are seen in muscles?
A
- denervation atrophy (follows loss of axon)
- myopathy (primary abnormality of muscle fiber)
4
Q
What is segmental demyelination?
A
- random internodes of myelin are injured and are remyelinated by multiple Schwann cells (smaller internodes)
- axon and myocytes remain intact
5
Q
How does an axon undergoing demyelination look on histology?
A
-cut in cross section: concentric layers (“onion bulbs”) of Schwann cytoplasm and redundant basement membrane surrounding thinly myelinated axon
6
Q
What structure(s) might be seen near axonal demyelination on histology?
A
-macrophages filled w/ lipid droplets from myelin degeneration
7
Q
What is a traumatic neuroma?
A
–failure of the outgrowing axons to find their distal target, producing a pseudotumor
–non-neoplastic haphazard whorled proliferation of axonal processes and associated Schwann cells
–painful nodule
8
Q
What is seen on histology of denervation atrophy?
A
- “angulated fibers” are smaller and triangular
- “target fibers” are rounded zones of disorganized myofibers in the center of a fiber
9
Q
True or False: growth cone of regenerating nerve fibers uses vacated Schwann cells as a guide
A
True
10
Q
How is muscle fiber type determined?
A
- muscle fiber type is determined by the neuron of that motor unit
- the fiber properties are imparted via innervation
11
Q
True or False: all muscle fibers of a single unit are the same type
A
True, the fiber type is determined by the motor neuron that innervates them
12
Q
How is the “checkerboard pattern” of muscle fiber types across a muscle achieved?
A
-fibers of a single unit (all the same type) are distributed across the muscle, not all clumped together
13
Q
What are the characteristics of Type 1 muscle fibers?
A
- -sustained force, weight-bearing
- -abundant lipids, scant glycogen
- -many mitochondria, wide Z-band
- -red, slow-twitch
14
Q
What are the characteristics of Type II muscle fibers?
A
- -sudden mvmts, purposeful motion
- -scant lipids, abundant glycogen
- -few mitochondria, narrow Z-band
- -white, fast-twitch
15
Q
What is Type Grouping and how might it have happened?
A
- patch of contiguous myocytes having the same histochemical type
- axons of a neighboring motor unit sprout to reinnervate denervated myocytes and incorporate them into the healthy motor unit
16
Q
What are some examples of etiology for Type II fiber atrophy (a form of group atrophy)?
A
- inactivity/disuse (ex: limb Fx, neurodegenerative Dz)
- glucocorticoid therapy (“steroid myopathy”)
17
Q
What is segmental necrosis of myocytes, in regards to muscle fiber pathologic reactions?
A
- destruction of a portion of myocyte
- followed by myophagocytosis
- deposition of collagen and fat
18
Q
What is vacuolization of myocytes, in regards to muscle fiber pathologic reactions?
A
- alterations in structural proteins or organelles
- accumulation of intracytoplasmic deposits
19
Q
Describe regeneration of myocytes, in regards to muscle fiber pathologic reactions.
A
- satellite precursor cells proliferate and reconstitute the destroyed portion of fiber
- the regenerating portion has large central nuclei w/ prominent nucleoli
- myocytes are RED (on a trichrome stain) bc of cytoplasm laden w/ RNA
20
Q
Describe hypertrophy of myocytes, in regards to muscle fiber pathologic reactions.
A
-response to increased load, exercise, or injured fibers
21
Q
What is Muscle Fiber Splitting and what is seen on histology?
A
- large fibers may divide longitudinally
- in cross section: single large fiber w/ a cell membrane traversing its diameter, often w/ adjacent nuclei
22
Q
How is the typical pain of peripheral neuropathy described?
A
- tingling
- stabbing
- burning
- “pins and needles”
23
Q
What is a mononeuropathy and its possible etiologies?
A
- affects a single nerve
- deficits in a restricted distribution
-d/t trauma, entrapment, infection
24
Q
What is a polyneuropathy?
A
- affects multiple nerves, usually symmetric
- deficits start at feet and ascend as dz progresses
-hands are usually affected about the same time as the knees are affected (“stocking and glove”)
25
What is mononeuritis multiplex, and a common etiology for this pattern of neuropathy?
-several nerves damaged in haphazard fashion
- commonly d/t vasculitis (ex: polyarteritis nodosum)
- also caused by HIV
26
What are polyradiculoneuropathies?
- affects nerve roots as well as peripheral nerves
| - diffuse symmetric distribution in proximal and distal parts of the body
27
What are the characteristics of Bell's Palsy, a mononeuropathy of CN VII?
- -typically affects those ages 15-60
- -resolves spontaneously
- -U/L facial droop, tingling, memory and balance issues
- -associated with URI and DM
28
What is a neurogenic bladder?
-any number of urinary conditions in people who lack bladder control d/t a brain, spinal cord or nerve problem
29
What are examples of conditions that can cause neurogenic bladders?
- MS
- Parkinson's
- DM
- spina bifida
- brain or spinal cord infection/injury/stroke
- heavy metal poisoning
- major pelvic surgery
30
What are the clinical features of Acute Inflammatory Demyelinating Polyneuropathy (Guillain-Barre)?
- acute onset
- weakness beginning in distal limbs
- "ascending paralysis"
- DTR's disappear
--can be life-threatening
31
What is Acute Inflammatory Demyelinating Polyneuropathy and some possible etiologies?
--immune-mediated inflammation and demyelination of spinal nerve roots and peripheral nerves (radiculoneuropathy)
--67% preceded by acute flu-like illness (Campy, CMV, EBV, Mycoplasma pneumoniae, or vaccine)
32
What is seen on histology of Acute Inflammatory Demyelinating Polyneuropathy?
-perivenular and endoneurial infiltration by lymphocytes, macrophages, and a few plasma cells
- segmental demyelination
- -anti-myelin antibodies
33
What is the pathogenesis of Acute Inflammatory Demyelinating Polyneuropathy?
-cytoplasmic processes of macrophages penetrate the BM of Schwann cells near the Nodes of Ranvier, and extend b/w myelin lamellae, stripping myelin sheaths away from the axon
34
What are the characteristics of CSF fluid in Acute Inflammatory Demyelinating Polyneuropathy?
- increased CSF protein
- little to no pleocytosis (cells in the CSF)
- -inflammatory cells remain confined to the roots
35
What is the treatment for Acute Inflammatory Demyelinating Polyneuropathy and the mortality rate?
- plasmapharesis, IVIg
- 5%
-20% of those hospitalized have permanent disability
36
What is the most common acquired inflammatory peripheral neuropathy?
-chronic inflammatory demyelinating polyradiculoneuropathy
37
What are the characteristics of chronic inflammatory demyelinating polyradiculoneuropathy?
- lasts 2+ mos
- symmetrical mixed sensorimotor polyneuropathy
- may relapse and remit over the years
- -clinical remission: immunosuppressive treatments (glucocorticoids, IVIg, plasmapharesis)
38
How can you distinguish Acute Inflammatory Demyelinating Polyneuropathy from Chronic?
- time course
| - RESPONSE TO STEROIDS
39
What is seen on histology of Chronic Inflammatory Demyelinating Polyradiculoneuropathy?
--complement-fixing IgG and IgM found on myelin sheath
--sural nerve biopsy: multiple layers of Schwann cells wrap around an axon like the layers of an onion
40
What is lepromatous leprosy?
-Mycobacterium leprae invades Schwann cells where it proliferates and infects other cells
- segmental demyelination and remyelination
- loss of both myelinated and unmyelinated axons
41
What is seen on histology of leprosy?
- endoneurial fibrosis
| - multilayered thickening of perineural sheaths
42
What are the clinical findings in lepromatous leprosy?
- symmetric polyneuropathy affecting cool extremities
- loss of sensation leads to injury (d/t loss of pain fibers)
- large traumatic ulcers
43
What is tuberculoid leprosy?
- -active cell-mediated response
- -granulomatous nodules in dermis
- -injures cutaneous nerves
- -localized nerve involvement
44
What neural component does Corynebacterium diptheriae attack and how do the clinical symptoms begin?
- affects the peripheral nerves
- begins w/ paresthesias and weakness
- early loss of proprioception and vibratory sensation
45
What is the gross morphology of diptheria?
-selective demyelination of axons that extend into adjacent anterior and posterior roots, and into mixed sensorimotor nerves
46
What is the most common viral infection of the PNS?
-varicella zoster virus
47
Where does varicella zoster virus like to "hang out"?
-sensory ganglia of the spinal cord and brainstem
48
What is Shingles?
- reactivation of latent varicella zoster infection
| - painful vesicular skin eruptions in distribution of sensory dermatomes
49
What are the neural consequences of shingles?
- neuronal destruction
- loss of affected ganglia
- axonal degeneration of peripheral nerves after death of the sensory neurons
- focal destruction of large motor neurons in anterior horns or cranial nerve motor nuclei
50
What is seen on histology of shingles?
- abundant mononuclear infiltrate
| - regional necrosis and hemorrhage
51
How does Lyme Disease affect the peripheral nervous system?
- in the 2nd and 3rd stages
- polyradiculoneuropathy
- U/L or B/L facial N. palsies
52
What is the most common cause of peripheral neuropathy?
DM
-most common pattern: ascending distal symmetrical sensorimotor neuropathy
53
What is the prevalence of peripheral neuropathy in patients with DM?
- depends on the duration of the Dz
- 50% overall
- 80% by the time they've had DM for 15 yrs
54
What is the clinical presentation of a patient with diabetic peripheral neuropathy?
- numbness, loss of pain sensation, balance problems
- paresthesias and dysesthesias (positive symptoms)
- chronic ulcers
- increased susceptibility to foot/ankle fractures
- diffuse vascular injury (major cause of morbidity)
55
What is seen on histology of segmental demyelination of DM?
-endoneurial arterioles show thickening, hyalinization, and intense PAS positivity
56
What are the symptoms of the autonomic dysfunction that can be seen in 30% of DM patients?
- postural hypotension
- incomplete emptying of bladder
- increased bladder infections
- sexual dysfunction
57
How does uremia affect the peripheral nervous system?
- axonal degeneration is usually the primary event
- -regeneration and recovery common after dialysis
- distal symmetric neuropathy
- muscle cramps
- distal dysesthesias
- decreased DTR's
58
How does thyroid dysfunction affect the peripheral nervous system?
- hypothyroidism is linked to compression mononeuropathies such as carpal tunnel syndrome
- distal symmetrical, predominantly sensory, polyneuropathy
59
What sorts of metal toxicities are associated with peripheral nervous system symptoms?
- LEAD
- mercury
- arsenic
- thallium
60
What chemotoxic agents are associated with peripheral nervous system symptoms?
- vinca alkaloids
- taxanes
- microtubule inhibitors
- cisplatin
61
How can malignancies cause neuropathies?
- -local effects
- -complications of Tx
- -paraneoplastic effects
- -tumor-derived Ig (B-cell tumors)
62
What is the most common malignancy to cause a paraneoplastic neuropathy, and what type of neuropathy does it cause?
- small cell lung CA
| - -sensorimotor neuropathy
63
What are the symptoms of a neuropathy caused by monoclonal gammopathies (B-cell neoplasms)?
```
Polyneuropathies
Organomegaly
Endocrinopathy
Monoclonal gammopathy
Skin changes
```
64
What are the characteristics of Carpal Tunnel Syndrome (a type of compression/entrapment neuropathy)?
- median nerve under the transverse carpal ligament
- frequently B/L
- more common in women
- numbness/paresthesia in thumb and first 2 digits
65
What are risk factors for developing Carpal Tunnel Syndrome?
- tissue edema
- pregnancy
- inflammatory arthritis
- hypothyroidism
- amyloidosis
- acromegaly
- DM
- excessive repetitive wrist motions
66
What is "Saturday Night Palsy"?
- radial nerve of the upper arm
| - from falling asleep awkwardly
67
What is the most common inherited peripheral neuropathy?
Charcot-Marie-Tooth
68
What are the characteristics of Charcot-Marie-Tooth Type 1?
- autosomal dominant
- PMP22 mutation (peripheral myelin protein 22)
- chr 17
- appears in teenagers
- slowly progressive demyelination motor and sensory
69
Regardless of etiology, what is the typical presentation of disorders that impair the function of the neuromuscular junction?
-painless weakness
70
What is the most common cause of disrupted nerve signal transmission?
--auto-antibodies that inhibit key neuromuscular junction proteins
(ex: myasthenia gravis and Lambert-Eaton)
71
How does clostridium botulinum affect neuromuscular junctions?
-blocks release of Ach
72
How does curare affect neuromuscular junctions?
-muscle relaxant that blocks the Ach receptor to cause flaccid paralysis
73
What is the demographic of patients affected by Myasthenia Gravis?
- bimodal age distribution
| - 2:1 female predominance (except in elderly, it predominates in males)
74
What is the pathogenesis of Myasthenia Gravis?
--immune-mediated loss of Ach receptors
--85% have circulating Ab's to Ach receptors
--15% have Ab's against muscle-specific receptor tyrosine kinase (a sarcolemmel protein)
75
The presence of Ach receptor Ab's has a strong association to abnormalities in what organ?
thymus
- 10% of myasthenia gravis patients have a thymoma
- 30% have thymic hyperplasia (B cell follicles present)
76
What is the clinical presentation of myasthenia gravis?
- fluctuating generalized weakness
- weakness worsens w/ exertion
- weakness worsens over the course of the day
- diminished responses after repeated stimulation
77
What clinical symptoms differentiate myasthenia gravis from other myopathies?
- weakness begins w/ extraocular muscles
- ptosis
- diplopia
-pts w/ Ab's to muscle-specific tyrosine kinase exhibit more focal muscle involvement (neck, shoulder, face)
78
What is the treatment for Myasthenia Gravis?
- -acetylcholinesterase inhibitors (increase Ach half-life)
- -plasmapharesis
- -immunosuppressants (glucocorticoids, rituximab
- -thymectomy (if thymoma present)
79
What is Lambert-Eaton Myasthenic Syndrome?
- Ab's block Ach release by inhibiting presynaptic Ca channels
- 50% of cases are a paraneoplastic syndrome associated with small cell carcinoma of the lung (the other half of cases are autoimmune)
80
True or False: the symptoms of Lambert-Eaton Myasthenic Syndrome can occur before lung cancer has even been diagnosed
True; sometimes LEMS precedes CA Dx by yrs
81
How does Lambert-Eaton Myasthenic Syndrome respond to repetitive stimulation?
-muscle response increases
| opposite of myasthenia gravis
82
How are muscles able to regenerate following injury?
- the myofibers are arranged in fascicles
- each fascicle is associated w/ a pool of stem cells
- -"satellite cells"
83
What is the normal muscle fiber pattern in skeletal muscle?
-checkerboard pattern with Type I and Type II fibers admixed
84
What type of atrophy does neurogenic disease cause?
-group atrophy by fiber type grouping
85
What type of atrophy does dermatomyositis cause?
-perifascicular atrophy
86
What type of atrophy is caused by prolonged corticosteroid use?
-Type II group atrophy
87
What will you see in the serum as myofibers degenerate?
-creatine kinase (marker of muscle damage)
88
How do regenerating muscle fibers appear on histology?
- stain basophilic d/t being rich in RNA
- enlarged nuclei w/ prominent nucleoli
- nuclei randomly distributed through cytoplasm (instead of along the periphery in normal cells)
89
What is the age demographic for those affected by dermatomyositis?
-30's to 50's
90
Describe the skin manifestations of dermatomyositis.
- lilac/heliotrope discoloration of upper eyelids
- periorbital edema
- telangectasias of nail folds, eyelids, and gums
-Gottron Lesions: erythematous eruptions or dusky patches on knuckles, elbows, and knees
91
Besides the skin manifestations, what are the symptoms of dermatomyositis?
- proximal muscle weakness (difficulty rising from chair)
- 33% develop dysphagia
- 10% develop interstitial lung dz and vasculitis
92
What auto antibodies can be found in dermatomyositis?
- -anti-Mi2
- -anti-Jo1
- -anti-P155 and P140 (in juvenile and paraneoplastic)
93
What underlying condition may be found in adults with dermatomyositis?
-20% have a malignancy
94
What can be seen on histology of dermatomyositis?
- perifascicular atrophy
| - mononuclear infiltrate in perimysial connective tissue
95
What are the characteristics of juvenile dermatomyositis?
- onset around 7yrs old
- most common myopathy in children
- involves GI tract
-calcinosis and lipodystrophy (instead of occult malignancy that can be found in adults)
96
What are the symptoms of polymyositis?
- myalgia
- weakness
- symmetrical proximal muscle involvement
- NO cutaneous features (unlike dermatomyositis)
97
What is seen on histology of polymyositis?
-CD8+ cytotoxic T-cells in endomysium
(unlike dermatomyositis in the perimysium)
-affected fibers are randomly distributed (unlike dermatomyositis which is perifascicular)
98
What is the age demographic for Inclusion Body Myositis?
- older than 50yrs
| - most common inflammatory myopathy for 65+yrs
99
Where is the most severe muscle weakness in Inclusion Body myositis?
- quads
- distal upper extremities
-starts w/ distal muscles
(knee extensors, and wrist/finger flexors)
-also involves dysphagia
100
What is seen on histology of Inclusion Body Myositis?
- rimmed vacuoles (inclusions w/ red granular rim)
| - endomysial fibrosis
101
What is the treatment for inflammatory myopathies such as dermatomyositis, polymyositis, and inclusion body myositis?
1st Line Tx: -corticosteroids
2nd Line Tx: if steroid-resistant, use immunosuppressive drugs such as azathioprine or MTX
3rd Line Tx: IVIg, cyclophosphamide, cyclosporine, or rituximab
102
How does inclusion body myositis respond to treatment?
-responds poorly to steroids and immunosuppressants
103
What is the most common complication of statins?
myopathy
104
What are the characteristics of toxic myopathy caused by antimalarial drugs such as chloroquine and HCQ?
- lysosomal storage myopathy
- slowly progressive muscle weakness
- affects Type 1 fibers
(chloroquine and hydroxychloroquine are used at long-term Tx for systemic autoimmune diseases)
105
What are the characteristics of ICU myopathy?
- aka Myosin Deficit Myopathy
- critical illness w/ corticosteroid use
- clinical course is affected by profound weakness
106
What is Thyrotoxic Myopathy?
-acute or chronic proximal muscle weakness
Exophthalmic Ophthalmoplegia: edema, diplopia
Hypothyroidism: cramps/aches; decreased mvmt; slowed reflexes
107
What are the characteristics of a myopathy caused by alcohol?
- binge drinking
- rhabdomyolosis
- myoglobinuria
- renal failure
- acute myalgia
108
What are the characteristics of congenital myopathies?
- present in infancy
| - tend to be static or improve over time
109
What are the characteristics of muscular dystrophies?
- progressive muscle damage
- symptoms appear after infancy
Congenital Dystrophies: present in infancy, developmental abnormalities of CNS, progressive muscle damage
110
What are two examples of X-linked muscular dystrophies?
-Duchenne
(more common, more severe, NO dystrophin)
-Becker
(decreased amt of dystrophin)
111
What is the normal role of dystrophin?
-forms an interface b/w the intercellular contractile apparatus and the extracellular connective tissue
(myocyte degeneration is caused by transferring the force of ctx to connective tissue in absence of dystrophin)
112
Describe pseudohypertrophy as it relates to Duchenne and Becker muscular dystrophies.
- enlargement of muscles of lower leg associated w/ weakness
- increased bulk is d/t the increased size of muscle fibers initially; later the increased bulk is d/t the increased amt of fat and connective tissue
113
What can be seen on histology of both Duchenne Muscular Dystrophy and Becker Muscular Dystrophy?
- variation in fiber size
- increased, centrally-located nuclei
- degeneration, necrosis, phagocytosis of muscle fibers
- regeneration of muscle fibers
- proliferation of endomysial connective tissue
Late Stage: muscle almost totally replaced by fat and connective tissue
114
What is myotonia?
- sustained involuntary contraction of a group of muscles
| - difficulty releasing a grip ("stiffness") can be elicited by percussion on thenar eminence
115
What are the symptoms of Myotonic Dystrophy?
- skeletal muscle weakness
- cataracts
- endocrinopathy
- cardiomyopathy
116
What are the genetics of Myotonic Dystrophy?
- autosomal dominant w/ anticipation
- CTG trinucleotide repeat at 19q13.2-q13.3
- myotonic dystrophy protein kinase
117
What is seen on histology of Myotonic Dystrophy?
- "ring fiber"
| - "sarcoplasmic mass"
118
What is the seen on gross appearance of a pt with Myotonic Dystrophy?
- gait abnormalities
- atrophy of facial muscles ("hatchet face")
- ptosis
- frontal balding
- cataracts
- cardiomyopathy
119
What are the characteristics of Emery-Dreifuss Muscular Dystrophy?
- -mutations in genes that code nuclear lamina proteins
- -X-linked form (EMD1)
- -autosomal dominant form (EMD2)
Triad of Symptoms:
- slowly progressive humeroperoneal weakness
- cardiomyopathy w/ conduction defects
- early contracture of Achilles tendon, spine, and elbow
120
What are the characteristics of Limb-Girdle Muscular Dystrophy?
- muscle weakness, mostly proximal muscle groups
- can be autosomal dominant or autosomal recessive
- variable onset and severity
121
What are the two major patterns of muscle dysfunction that are seen in diseases that involve problems w/ lipid or glycogen metabolism?
- symptoms appear w/ exercise and fasting
- -severe muscle cramps, pain
- -extensive muscle necrosis (rhabdomyolysis)
-slowly progressive muscle damage
122
What is the most common disease of lipid or glycogen metabolism?
- Carnitine Palmitoyltransferase II Deficiency
| - -episodic muscle damage w/ exercise and fasting
123
What is McArdle Disease?
- myophosphorylase deficiency
- a glycogen storage disease
- episodic muscle damage w/ exercise
124
What is Pompe Disease?
- acid maltase deficiency
| - there is an adult form that is milder (affects respiratory and trunk muscles)
125
What are the characteristics of mitochondrial myopathies?
- maternal inheritance
- impaired ability to generate ATP in mitochondria
-symptoms: weakness, increased serum CK (marker of rhabdomyolysis), chronic progressive EXTRAOCULAR MUSCLE weakness is common
126
What are some examples of mitochondrial myopathies?
Leber Hereditary Optic Neuropathy: mtDNA point mutation
Leigh Syndrome: nuclear DNA mutation; subacute necrotizing encephalopathy
Barth Syndrome: nuclear DNA mutation; infantile X-linked cardioskeletal myopathy
Kearns-Sayre Syndrome: deletion of mtDNA: weakness of extraocular eye muscles; pigmentary degeneration of retina, complete heart block
127
What are "ragged red fibers"?
- aggregates of abnormal mitochondria under the sarcolemma (RED on trichrome stain)
- distortion of myofibrils (RAGGED)
128
What are the characteristics of Spinal Muscular Atrophy?
- neuropathic disorder
- loss of motor neurons
- muscle weakness and atrophy
- generalized hypotonia ("floppy infant")
129
What part of the nervous system is destroyed in Spinal Muscular Atrophy?
-anterior horn cells of spinal cord
130
What is the inheritance of Spinal Muscular Atrophy?
- autosomal recessive
| - mutation of Survival Motor Neuron 1 (SMN1) on chr5
131
What is seen on histology of Spinal Muscular Atrophy?
-large zones of atrophic myofibers mixed w/ scattered normal or hypertrophied myofibers
132
What is Wernig-Hoffman (SMA Type 1), the most common type of Spinal Muscular Atrophy?
- onset at birth
- floppy baby
- death by age 3
- muscle weakness of trunk and extremities initially
- later: chewing, swallowing and breathing difficulties
133
What is the inheritance pattern for most channelopathies?
autosomal dominant
134
What are symptoms of a channelopathy?
- epilepsy
- migraine
- mvmt disorders w/ cerebellar dysfxn
- peripheral nerve dz
- muscle dz
135
What mutation causes Malignant Hyperthermia (a type of channelopathy)?
-RYR1 (ryanodine receptor 1)
- sometimes this mutation also causes Central Core Dz
- -"floppy infant"
- -scoliosis
- -hip dislocation
- -foot deformities
136
What are the symptoms of malignant hyperthermia?
- tachycardia
- tachypnea
- muscle spasms
- hyperpyrexia
(basically, a hypermetabolic state)
137
What is a common trigger for malignant hyperthermia?
-halogenated inhalational anesthetic agents
--trigger an efflux of Ca2+ from sarcoplasmic reticulum which causes tetany and excessive heat
138
What are the characteristic features of NF-1?
- optic pathway glioma
- brainstem glioma
- neurofibromatosis
- cafe au lait spots
- axillary freckling
- Lisch nodules
139
What are the characteristic features of NF-2?
- B/L acoustic Schwannomas
- multiple meningiomas
- ependymomas
- NF2 plaque
- subcutaneous Schwannomas
140
What are the characteristic features of Retinoblastoma?
- pineoblastoma
| - leukokoria
141
What are the characteristics features of Von Hippel Lindau Dz?
- hemangioblastoma of cerebellum, spine, or retina
- polycythemia
- cysts of pancreas, liver, or kidneys
- renal cell carcinoma
- pheochromocytoma
142
What are the characteristics features of Tuberous Sclerosis?
- subependymal giant cell astrocytoma
- ash leaf spots
- retinal astrocytomas
143
What is the inheritance pattern of Tuberous Sclerosis?
-autosomal dominant
144
What are the genes, chromosomes, and proteins affected in Tuberous Sclerosis?
- TSC1; chr9q34; hamartin
| - TSC2; chr16q13.3; tuberin
145
What are the neurologic symptoms of Tuberous Sclerosis?
- seizures
- autism
- mental retardation
146
What is seen on physical exam of Tuberous Sclerosis?
- hamartomas (epileptogenic cortical tubers)
- renal angiomyolipomas
- pulmonary lymphangioleiomyomatosis
- cardiac rhabdomyomas
- angiofibromas
- subungual fibromas
- shagreen patches (localized cutaneous thickening)
- ash leaf patches (hypopigmented areas)
147
What is the inheritance pattern of Von Hippel-Lindau Dz?
-autosomal dominant
148
What is the gene and chromosome affected in Von Hippel-Lindau Dz?
- VHL at chr3p25.3
| - tumor suppressor gene that regulates EPO
149
Which is more common, NF-1 or NF-2?
NF-1
150
What is the inheritance of NF-1 and NF-2?
autosomal dominant
151
How does the anatomy of a Schwannoma differ from the anatomy of a neurofibroma?
Schwannoma
- encapsulated
- separable from the nerve
- Schwann cells
Neurofibroma
- not encapsulated, within the nerve itself
- mix of Schwann cells and fibroblasts
- axons admixed
152
What are the characteristics of a Schwannoma?
- S100+
- typical at the cerebellar pontine angle
- common in NF2 w/ loss of merlin
- acoustic neuroma when it affects CN VIII
- -causes tinnitus and hearing loss
153
What do you see on histology of NF2?
- Antoni A = spindle cells
- Antoni B = hypocellular, myxoid extracellular matrix
-Verocay Bodies = palisading nuclei around "nuclear free zones"
154
What are the characteristics of a Malignant Peripheral Nerve Sheath Tumor?
- 85% are high grade tumors
- 50% arise in NF1 patients
-Triton Tumor is a subtype w/ rhabdomyoblastic differentiation
