Peripheral N & Skeletal M Path Flashcards
Segmental demyelination process
Schwann cell dysfunction leads to damage of the myelin sheath. Random internodes of myelin are injured (denuded axon) and remyelinated by multiple Schwann cells while the axon and myocytes remain intact. (Ex. Guillain-Barre Syn)
How can you tell internodes are newly myelinated?
They are shorter than normal and take several to bridge the demyelinated region
What is axon damage?
Axon damage affects whole neuron body or axon
What is a focal lesion
traumatic transection of an axon, the distal portion undergoes Wallerian degeneration
What are myelin ovoids?
Schwann cells that catabolize myelin & later engulf axon fragments producing small oval compartments
If you see triangular ‘angulated’ muscle fibers what process has happened?
Denervation atropy
Axonal degeneration -> muscle fibers in motor unit lose neural input -> DA
What determines muscle fiber type?
Motor neuron determines fiber type
Type 1 v Type 2 neurons. (more for boards)
1 - Sustained force, weight bearing, red, slow-twitch. Lots of lipids with low glycogen
2 - sudden movements, purposeful motion, white, fast-twitch. Lots of glycogen with low lipids
What would cause group atrophy of type 2 fibers?
Inactivity or disuse (limb fracture, pyramidal tract degeneration, neurodegenerative dz)
Glucocorticoid therapy -> steroid myopathy
What are the pathologic reactions of myoctes? (4)
Segmental necrosis - loss of muscle fiber -> deposition of collagen and fat (Ex. Duchenne’s muscular dystrophy)
Hypertrophy - muscle fiber splitting; response to increase load
Regeneration - large internalized nuclei with prominent red RNA under trichrome stain
Vacuolization
Describe the findings of peripheral neuropathy?
Tingling, stabbing, burning or “pins and needles”
Difference between mononeuropathies and polyneuropathies?
Mono - involve a single nerve & deficits are restricted to region
Poly - multiple nerves are involved, usually symmetrically. Deficits ascend with dz progression (stocking & glove distribution)
What is Mononeuritis multiplex and the associated dz’s?
Several nerves damaged in haphazard fashion.
Assoc. with vasculitis like polyarteritis nodosum (PAN)
Ex. HIV
What is affected in polyradiculoneuropathies?
Nerve roots and peripheral nerves
Bell’s Palsy
Mononeruopathy of CN VII
Asymmetrical facial drop assoc. with URI & DM. Usually resolves spontaneously
What is Neurogenic bladder and the dz’s assoc. with it?
Lack of bladder control due to brain, spinal cord or nerve problem.
Assoc. with MS, Parkinson’s, DM, infections, or spina bifida.
Issue with nerves to bladder can cause overactive or underactive bladder
Guillain-Barre
Acute inflammatory immune-mediated demyelinating polyneuropathy.
Anti-myelin abs are produced.
Segmental demyelination with perivenular and endoneurial infiltration.
Weakness begins in distal limbs with ascending paralysis. DTR’s disappear.
Incr. CSF production. Tx with plasmaphreresis or IVIg
Chronic Inflammatory Demyelinating Poly(radiculo)neropathy
Most common aquired inflammatory peripheral neuropathy. Symmetrical and >2mo. Responds to steroids unlike GB! Sural nerve bx shows ONION BULBS
Leprosy (Hansen dz)
Mycobacterium leprae cause segmental demyelination and loss of BOTH myelinated and unmyelinated axons. Endoneurial fibrosis and multilayered thickening of perineural sheaths occurs.
Symmetric polyneuropathy affects cool extremities. Pain fiber involvement & loss of sensation contribute to injuries. AFB (+)
TB Leprosy
Granulomatous nodules in dermis. localized to nerve involvement. AFB (+)
Diptheria
Exotoxin affects peripheral nerves beginning with paresthesias and weakness. Loss of proprioception and vibratory sensation early.
VZV
Most common viral infection of PNS. Ascends to CNS via sensory ganglia. Reactivation of the virus = Shingles.
Loss of affected ganglia, necrosis & hemorrhage can be seen. Axonal degen. of PN after death of sensory neurons. Focal destruction of large motor neurons in anterior horns or CN motor nuclei.
Peripheral neuropathy in DM
Most common cause of peripheral neuropathy, ascending distal symmetric sensorimotor polyneuropathy.
Sx: Numbness, loss of pain sensation, difficulty balancing. Paresthesias & dysesthesias. Diffuse vascular injury
Endoneurial arterioles show thickening, hylinization & intense PAS (+)
Thyroid dysfunction
hypothyroidism -> compression mononeuropathies.
Neuropathies assoc with monocolonal gammopathies (B-cell neoplasms)
POEMS: polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes
Traumatic neuroma
small bundles of axons randomly orient after break in axon. Surrounded by organized layers of Schwann cells fibroblasts & perineural cells
Compression/entrapment neuropathy
Carpel tunnel syn - median N. affecting thumb and first two fingers
Saturday night palsy - Radial n. Ex. falling asleep awkwardly.
Ulnar N. at elbow or peroneal N at knee
Morton neuroma - metatarsalgia, histological lesion=perineural fibrosis
(3) inherited peripheral neuropathies
Charcot-Marie-Tooth (CMT) - AD
Familial Amyloid Polyneuropathies (FAP) - amyloid dep in PNs
Metaboli DOs
Myasthenia gravis
More common in women. Circulating autoAbs. to AchR. Assoc. thymoma & thymic hyperplasia. Diminished responses after repeated stim. (worsens with exertion).
Tx: plasmapheresis & immunosuppression. Thymectomy
Lambert-Eaton Syn
Ab block of Ach release by inhibition of presynaptic Ca2+ channel. Assoc. as paraneoplastic syn. with small cell carcinoma of the lung. Repetitive stim. incr. muscle response!
Dermatomyositis has atrophy of what part of the nerve? What are the clinical sx? Assoc. organs affected? Antibodies?
Perifasicicular atrophy.
Lilac or heliotrope eyelids with periorbital edema. Telangiectasias. Grotton lesions on elbows, knees and knuckles. Proximal m. first so pts have trouble rising from chair. Interstitial lung dz and cardiac involvement with incr. risk for visceral cancers.
Anti-Mi2, anti-Jo1, and anti=P155/P140
Polymyositis
Myalgia & weakness. Symmetrical proxima muscle involvement. Lacks cutaneous involvement. Endomysial infiltrates and random distribution of atrophy
Inclusion body myositis
> 50 yo. Slowly progressivemuscle weakness most severe in quadriceps and distal extremities. Dysphagia. Rimmed vacuoles DOES NOT RESPOND TO STEROIDS OR IMMUNOSUPPRESSION
How do you tx dermatomyositis and polymyositis?
Corticosteroids & immunosuppression
Drugs and tx’s that can cause toxic myopathies?
Statins, antimalarial drugs, ICU myopathy, Thyrotoxic myopathy, alcohol.
Duchenne Muscular dystrophy
X-linked, Xp21 gene. No dystrophin. Pseudohypertrophy
Becker Muscular dystrophy
X-linked, Cardiac dz, decr. amount of dystrophin. Pseudohypertrophy
Myotonic dystrophy
Myotonia sometimes elicited by percussion on thenar eminence. Stiffness & difficulty releasing grip. AD. CTG trinucleotide repeat
Sx: skeletal m weakness, cataracts, endocrinopathy & cardiomyopathy. Hatchet face
Mitochondrial myopathies
sx: weakness, incr. serum CK or rhabdomyolysis. Extraoccular m involvement. Chronic progressive external ophthalmoplegia. (Leber, Leigh, Barth, Kearns- Sayre)
Spinal muscular atrophy
Generalized hypotonia of infant. AR SMN1 on Ch 5. Wernig-Hoffman is the most common. Destruction of the anterior horns. Death <3yo
RYR1 mut
Malignant hyperthermia! Signs of tachycardia, tachypnea, muscle spasms & hyperpyrexia. Anesthetic triggers large efflux of Ca2+. Tx with dantrolene
Neurofibromatosis Type 1
Neurofibromas of PN, optic N glioma, lisch nodules & cafe au lait spots. “Bag of worms” on histo. MPNST transformation possible
Neurofibromatosis Type 2
Bilateral schawnnomas (S100+) in CN VIII at cerebellopontine angle. Incr meningiomas and ependymomas
