Peripheral Nervous System and Skeletal Muscle Path Flashcards
segmental demyelination
schwann cell dysfunction secondary to damage of the myelin sheath
no primary abnormality of axons
what is a histo sign of demyelination?
onion bulbs = concentric layers of schwann cytoplasm and redundant basement membrane surrounding thinly myelinated axon
traumatic neuroma
failure of the outgrowing axons to find their distal target can produce a pseudo-tumor
painful nodule
axonal degeneration
primary destruction of axon with secondary disintegration of myelin sheath
axon damage
focal or generalized trauma or ischemia affecting the whole neuron body or its axon
describe the process of axonal degeneration
- myelin ovoids form due to engulfed axon fragments
- macrophages clean up
- proximal stump of severed nerve shows degenerative changes in distal 2-3 internodes
- axon undergoes regeneration
what happens to muscle fibers during axon degeneration?
lose neural input and undergo denervation atrophy resulting in angulated and target fibers
what reactions occur within the muscle fiber with damage?
segmental necrosis
vacuolization
regeneration
hypertrophy
what are the different anatomical patterns of peripheral neuropathies?
mononeuropathy - single nerve
polyneuropathy - multiple nerves
mononeuritis multiplex - multiple nerves in a haphazard fashion
polyradiculopathy - nerve roots + peripheral nerves
Bell’s palsy
mononeuropathy of CN VII causing facial muscle paralysis
what is the clinical presentation of bell’s palsy?
one sided facial droop
associated with URI or DM
facial tingling
headache
what is the ddx for facial droop?
Bell's palsy stroke brain tumor Ramsay hunt syndrome Lyme dz
what are the causes of neurogenic bladder?
nerve damage secondary to MS, Parkinsons or DM
infection of the brain or spinal cord
heavy metal poisoning
stroke
spinal cord injury
spina bifida
Guillain-Barre
acute inflammatory demyelinating polyneuropathy
ascending paralysis
inflammation of demyelination of spinal nerve roots and peripheral nerves
immune-mediated
what organisms can cause GB?
C. jejuni
CMV
Ebstein Barr
Mycoplasma pneumoniae
what is the etiology of GB?
inflammation of peripheral nerves by lymphocytes, macrophages and plasma cells
macrophages penetrate Schwann cells at the nodes of Ravier and strip myelin away from axon
what lab results can support GB?
increased CSF protein
anti-myelin antibodies
treatment of GB
plasmapheresis and IV Ig
chronic inflammatory demyelinating polyradiculopathy
most common acquired inflammatory peripheral neuropathy
symmetrical mixed sensorimotor polyneuropathy > 2 months
what distinguishes chronic inflammatory demyelinating polyradiculopathy from GB?
time of course
response to steroids
chronic inflammatory demyelinating polyradiculopathy diagnostic tools
sural nerve biopsy showing onion bulbs
complement-fixing IgG and IgM on myelin sheath
Leprosy/Hansen disease
schwann cells invaded by mycobacterium leprae
bacteria proliferates and infects other cells
what is the pathology underlying the symptomatology of leprosy
segmental demyelination
endoneurial fibrosis and thickened perineural sheaths
symmetric polyneuropathy affecting cool ext
what is the presentation of leprosy?
loss of sensation
large traumatic ulcers
diptheria neuropathy
Diptheria exotoxin damage to peripheral nerves
what is the presentation of Diptheria neuropathy?
paraesthesias weakness loss of vibratory sense loss of proprioception loss of respiratory muscle function if untreated
what is the most common viral infection of the PNS?
varicella zoster virus
shingles
reactivation of latent infection causing painful vesicular skin eruption in the distribution of sensory dermatomes
what is the pathology of shingles?
neuronal destruction and loss of affected ganglia
regional necrosis and hemorrhage
axonal degeneration of peripheral nerves after death of sensory neurons
focal destruction of large motor neurons in anterior horns or cranial nerve motor nuclei
lyme dz neuropathy
unilateral or bilateral facial nerve palsies
HIV neuropathy
mononeuritis multiplex
demyelinating disorder resembling GB
later stages associated with distal sensory neuropathy
what is the most common cause of peripheral neuropathy?
DM
presentation of diabetic neuropathy
symmetric neuropathy involving distal sensory and motor nerves:
numbness loss of pain sensation difficulty with balance diffuse vascular injury autonomic dysfunction
what is the etiology of diabetic neuropathy?
segmental demyelination
thickened endoneurial arterioles
what else can cause neuropathy?
uremia thyroid dysfunction vitamin deficiency EtOH heavy metals chemotherapy
what causes neuropathy associated with malignancy?
direct infiltration or compression of peripheral nerve
what are the signs of neuropathies associated with monoclonal gammopathies?
POEMS: polyneuropathy organomegaly endocrinopathy monoclonal gammopathy skin changes
what are some examples of compression/entrapment neuropathy?
carpel tunnel - median nerve
saturday night palsy - radial nerve
morton neuroma - interdigital nerve
what is the most common inherited PN?
Charcot-Marie-Tooth
what are the subtypes of CMT?
CMT1
CMTX
CMT2
CMT1
AD mutation on chrom 17 PMP22 gene
second decade of life
slowly progressive demyelinating motor and sensory
CMTX
X-linked form of Charcot-Marie-Tooth
CMT2
AD mutation on MDN2 gene
early childhood
familial amyloid polyneuropathies
amyloid deposition within the peripheral nerves
what inherited metabolic disorders can cause neuropathy?
leukodystrophies
porphyria
Refsum dz
what toxins block ACh release from the neuromuscular junction?
Clostridium botulinum
Curare
myasthenia gravis
autoantibodies to AChR at the neuromuscular junction
what is frequently associated with MG?
thymoma
thymic hyperplasia
what is the presentation of MG?
fluctuating generalized weakness that worsens with exertion and over the course of the day
diminished response after repeated stimulation
what is usually the first sign of MG?
extraocular muscle weakness - ptosis and diplopia
MG tx
AChE inhibitors
plasmapheresis
immunosuppressives
thymectomy
Lambert Eaton Myasthenic Syndrome
antibodies block ACh release by inhibiting presynaptic calcium channel
50% paraneoplastic process due to small cell carcinoma of the lung
what is the presentation of LEMS?
proximal muscle weakness and autonomic dysfunction
repetitive stimulation increases muscle response
dermatomyositis
autoantibodies
anti-Mi2
anti-Jo1
anti-P155/P140
what is the presentation of dermatomyositis?
lilac or heliotrope rash with periorbital edema telangiectasias Grotton lesions proximal muscle weakness dysphasia
dermatomyositis puts you at an increased risk to develop what?
visceral cancer
what is seen on histo in dermatomyositis?
perifascicular atrophy
perimysial mononuclear infiltrates
what is the common presentation of juvenile dermatomyositis?
onset at 7 y/o
involves GI tract
calcinosis and lipodystrophy
polymyositis
adult-onset myalgia and weakness due to CD8 Tcells in endomysium
symmetrical proximal muscle involvement
No cutaneous involvement
what is seen on histo with polymyositis?
endomysial mononuclear infiltrates
random distribution of affected fibers
inclusion body myositis
dz of late adulthood
slowly progressive muscle weakness most severe in quads and distal upper extremities
dysphagia common
what is on histo in Inclusion Body Myositis?
rimmed vacuoles
what is the treatment for inflammatory myopathies?
steroids
immunosuppressives if steroid-resistant
what toxins can cause myopathy?
statins chloroquine/hydroxychloroquine critical illness thyrotoxic alcohol
Duchenne MD
X linked mutation in Xp21
NO dystrophin production
sx before 5 y/o
wheelchair by 10-12 y/o
Becker MD
X linked mutation in Xp21
reduced dystrophin production
what is pseudohypertrophy?
enlargement of muscles of LE associated with weakness
increased bulk due to increased size of muscle fibers
replaced by fat and CT as MD progresses
what is seen on histo in both DMD and BMD?
variation in fiber size
increased internalized nuclei
degeneration, necrosis and phagocytosis of fibers
regeneration of fibers
proliferation of endomysium
fibers replaced by fat and CT (late stages)
what is seen in DMD histo but not BMD?
enlarged, rounded hyaline fibers that have lost their cross striations
myotonic dystrophy
AD mutation in DMPK gene due to CTG trinucleotide repeats
*anticipation
what is the presentation of myotonic dystrophy?
myotonia muscle weakness "hatchet face" cataracts endocrinopathy cardiomyopathy
what is seen on histo with myotonic dystrophy?
ring fiber
sarcoplasmic mass
Emery-Dreifuss MD
X linked EMD1 or AD EMD1 mutations in gene encoding lamina proteins
EMD triad of symptoms
humeroperoneal weakness
cardiomyopathy
early contractures of Achilles, spine and elbow
Limb-Girdle MD
AD or AR disease
muscle weakness that involves proximal muscle groups
carnitine palmitoyltransferase II def
episodic muscle damage with exercise and fasting
McArdle Dz/myophosphorylase def
episodic muscle damage with exercise
Pompe dz/acid maltase def
infancy: generalized glycogenesis
adult: respiratory and trunk muscle weakness
what are the mitochondrial myopathies?
Leber
Leigh
Barth
Kearns-Sayre
Leber syndrome
point mutation in mtDNA
optic neuropathy
Leigh syndrome
nuclear DNA gene mutation
subacute necrotizing encephalopathy
Barth syndrome
nuclear DNA gene mutation
infantile x-linked cardioskeletal myopathy
Kearns-Sayre syndrome
deletion of duplication in mtDNA
ophthalmoplegia
pigmentary degeneration of retina
complete heart block
what can be seen in histo for mitochondrial myopathies?
ragged red fibers
spinal muscular atrophy
AR mutation in SMN1 on Ch. 5 causing destruction of anterior horn cells
loss of motor neurons leading to muscle weakness and atrophy
what is the presentation for SMA?
generalized hypotonia/”floppy infant”
what is on the ddx for infantile hypotonia?
congential masthenic syndrome congenital myotonia congenital myopathies congenital MD encephalopathy neuronopathies (SMA)
what is the most common type of SMA?
Wernig-Hoffman disease
onset at birth
death < 3 y/o
what is the presentation of Wernig-Hoffman disease?
truncal and extremity weakness
chewing, swallowing and breathing difficulties
malignant hyperthermia
AD mutation in RYR1 gene causing channelopathy
hypermetabolic state causing tachycardia, tachypnea, muscle spasm, and hyperreflexia
triggered by anesthetics
