Msk Flashcards
2 main responses of peripheral nerve injury determined by target
Schwann-segmental demyelination -loss of myelin
Axon-axonal degeneration primary involvement of neuron and its axon, axonal degeneration may be followed by axonal regenerationa nd reinervation of muscle
Enervation atrophy
Follows loss of axon
Myopathy
Primary abnormality of msucle fiber
Segmental demyelination
Schwann cell damage to myelin sheath-Guillain barre
No primary abnormality of axon
Not affect all schwann cells
Denuded axon
Stimulus for demyelination
Newly myelinated internodes
Shorter than normal
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 make pseudotumor termed traumatic neuroma -a non neoplastic haphazard whirled proliferation of axonal processes and associated schwann cells that results in.a painful nodule-haphazard axons, schwann cells and connective tissue
Axonal degeneration
Axonal degeneration-result of primary destruction of axon with secondary disintegration of myelin sheath
Axon damage
Focal or generalized affecting whole neuron body (neuronopathy) or its axon (axonopathy)
Wallerian degeneration
Focal lesion distal portion
Myelin ovoids
Schwann cells catabolize myelin and later engulf axon fragments, producing small oval compartments
Then macrophages recruited
Proximal stump of severed nerve shows degenerative changes in most distal 2-3 internodes, then undergoes regeneration
Slowly evolving neuronopathies or axonopathies, scant evidence of axonal degeneration bc few fibers effecting at ant one time
Enervation atrophy
Axonal degeneration->muscle fibers in motor unit lose neural input and undergo denigration atrophy
Angulated fibers
Atrophic fibers are smaller and triangular shape when enervation atrophy
Target fibers
Rounded zone of disorganized myofibers in center fiber
How do we get growth of regenerating fibers: where does guide come from
Schwann cells vacated by degenerating axons
Regenerating cluster
Multiple closely aggregated thinly myelinated small caliber axons
Reinnervation fo skeletal muscle changes its composition, altering distribution of
The 2 major fiber tubes
__ __ determines fiber type; all muscle fibers of a single unit are the same type
Motor neuron
Fibers of a single unit are distributed across the muscle ___ __
Checkerboard pattern
Axons of unaffected neighboring motor unit extend sprouts to __ and __ ___ and incorporate them into the _____
Reinnervate
Denervated myocytes
Healthy motor unit
Newly adopted reinnervated fibers assume fiber type of their __ __
New siblings
Type grouping
Patch of contiguous myocytes having same histochemical type
Group atrophy
Type group becomes denervated
Type 2 fiber atrophy
Inactivity or disues (neurodegenerative dz)
Steroid myopathy-glucocorticoid use
Segmental necrosis
Destruction of a portion of myocytes, followed by myophagocytosis; loss of msucle fiber leads to deposition of collagen and fat
Muscle reaction seen in many diseases
Vacuolixation, alterations in structural proteins or organelles and accumulation of intracytopalsmic deposits
Reactions of muscle fibers
Segmental necrosis
Vacuolization, alterations in structural proteins or organelles and accumulation of intracytopalsmic deposits
Regeneration
Hypertrophy-muscle fiber splitting
Regeneration of muscle fiber
Satellite precursor cells proliferate and reconstitute the destroyed portion of fiber; regenerating portion has large internalized )central location) nuclei with prominent nucleoli; cytoplasm laden with RNA is RED
Hypertrophy muscle fiber
Response to increase load either through exercise or pathological conditions
Muscle fiber splitting
Large fibers may divide longitudinally; cross section=single large fiber with a cell membrane transversing its diameter, often with adjacent nuclei
Peripheral neuropathy pain
Tingling, stabbing, burning, or pins and needles
Mononeuropathies
Affect single nerve, deficits to nerve distribution
Polyneuropathies
Multiple nerves, usually symmetric
Deficits start at the feet and ascend with disease progression
Hand usually deficits same time as knee=stocking and glove distribution
Mononeuritis multiplex
Several nerves damaged in haphazard fashion
Vasculitis is a common cause of this pattern (polyarthritis nodosum-PAN)
Polyradiculoneuropathies
Nerve roots as well as peripheral nerves
Diffuse symmetric in proximal and distal parts of the body
Asymmetric peripheral neuropathy-multiple mononeuropathy
Bell’s palsy
Mononeuropathy
CNVII facial muscle paralysis
Resolves spontaneously
One sided facial droop within 48-72 horus
—URI and DM
-facial tingling , mid severe HA/neck pain , memory problems, balances issues, ipsilateral limb paresthesia, ipsilateral limb weakness
Neurogenic bladder
No bladder control from brain and spinal cord or nerve problem
MS, parkinson, diabetes nerve damage
Infection
Spina bifida
Overactive, underactive, Obstructive, flow
Peripheral nerve diseases
Inflammatory neuropathies
Infectious polyneuropathies
Hereditary neuropathies
Acquired metabolic and toxic neuropathies
Traumatic neuropathies
Gillian barre
Acute inflammatory demyelinating polyneuropathy of PNS
Ascending paralysis start legs and DTR disappear
Inflammation and demyelination of spinal nerve roots and peripheral nerves(radiculoneuropathy)
ACUTE ONSET immune mediated demyelinating neuropathy
Pathogenesis Gillian barre
Preceded by acute influenza like illness
Campylobacter jejuni, CMV, epstein Barr, mycopalsma Pneumonias, propria vaccination0
Perivenular and endoneurial inflammation
Segmental demyelination mainly peripheral nerves
Anti myelin antibodies
In Gillian barre cytoplasmic processes of ___ penetrate the BM of __ cells , in the _____ and extend between myelin lamellae stripping myelin sheath away from axon
Macrophages
Schwann
Nodes of ranvier
Increased CNS protein production in Gillian barre
Due to altered permeability of microcirculation of spinal roots
-inflammatory cells remain confined to the roots, thus little or no CSF pleocytosis
Treat Gillian barre
Plasmapheresis IVIg
Many have long term disability
Chronic inflammatory demyelinating polyneuropathy
Most common peripheral neuropathy
Symmetrical mixed sensorimotor polyneuropathy >2 months (NEED 2 moths)
Relapses and remits
Diagnose chronic inflammatory demyelinating polyrediculoneuropatthy
Time, response to steroids distinguish from Gillian barre
Sign of chronic inflammatory. Demyelinating poly(radiculoneuropathy
Onion bulbs
What are onion bulbs
Multiple layers of schwann cells wrap around an axon like the layers of an onion
Infectious polyneuropathies
Leprosy
Diptheria
Varicella zoster virus
Leprosy: lepromatous
Schwann ells invaded by mycobacterium leprae
Segmental demyelination and remyelination and loss of both myelinated and unmyelinated axons
Endoneurial fibrosis and multilayered thickening of perineural sheath
Symmetric polyneuropathy affecting cool extremities
Involves pain fibers, loss of sensation contributes to injury
Large traumatic ulcers
Tuberculoid leprosy
Active cell mediated response
Granulomatous nodules in dermis
Localized nerve involvement
Injures cutaneous nerves
Axons, schwann cells and myelin lost
Fibrosis and perineurium and endoneurial
Siptheria
Exotoxins affects peripheral nerves and begins with paresthesia and weakness
Early losss of proprioception and vibratory sensation
Sensory ganglia
Selective demyelination of axons that extend into adjacent anterior and posterior roots and into mixed sensorimotor nerves
Periph neuropathy assoc with prominent bulbar and respiratory msucle dysfunction->death or long term disability
Varicella zoster
Most common viral infection of PNS
Sensory ganglia
Reactiation of latent -shingles
Neuronal destruction and loss of affected ganglia; abundant mononuclear infiltrate; regional necrosis and hemorrhage may be found
Axonal degeneration of peripheral nerves after death of sensory neurons
Focal destruction of large motor neurons in anterior horns or cranial nerve motor nuclei may be seen at corresponding levels
Diabetes
Most common cause of peripheral neuropathy
Ascending distal symmetric sensorimotor polyneuropathy -prevelance of complication depends on duration of DZ. 50% of DM overall; 80% with DM>15 ye
Most common symmetric neuropathy involving distal sensory and motor nerves
-numbness, loss of pain sensation, difficult with balance, paresthesia and dysesthesias-positive sx=painful sensation , diffuse vascular injury major cause of morbidity in diabetes
Foot ankle skin ulcers
Segmental demyelination of DM neuropathy
Small myelinated fibers and unmyelinated fibers
Decrease axons ; degeneration myelin sheaths and regeneration of axonal clusters
Dysfunction of autonomic nervous system DM neuropathy
20-40% with distal sensorimotor neuropathy-postural hypotension, incomplete emptying of bladder and sexual dysfunction
Hypothyroidism
Compression mononeuropathies, distal symm predominantly sensory polyneuropathy
Rarely hyperthyroidism associated with syndrome resembling Gillian barre
Other toxic neuropathies
B12, b1, b6, folate, vit E , pb, PB, ethanol
Paraneoplastic neuropathies
Sensorimotor neuropathy =small cell lung cancer
POEMS
B celll neoplasm
Polyneuropathy, organometallic, endocrinopathy, monoclonal gammopathy and skin changes
Deposition of paraprotein between noncompacter myelin lamellae
Traumatic neuroma
Regenerates slowly ; discontinuity complicates
-small bundles of axons randomly oriented, but surrounded by organized layers of schwann cells, fibroblasts and perineural cells
Compression/entrapment neuropathy
Carpal tunnel
Saturday night palsy
Morton neuroma
Carpel tunnel
Median nerve
Saturday night palsy
Radial nerve upper arm
Morton neuroma
Metatarsalgia, histological lesion=perineural fibrosis
-interdigital nerve and intermetatarsal sites W>M
Charcot marie toothe
Most common inherited PN
Familial polyneuropathies
Amyloid deposition within the peripheral nerves
Metabolic DOs
Leukodystrophies, porphyria, refsum
C diff botox
Blocks release ach
Curare
Muscle relaxant blocks archer->flaccid paralysis
Myasthenia gravis
Circulation autoantibodies to achr
Thymoma thymic hyperplasia
Muscle specific receptor tyrosine kinase
Myasthenia gravis
Autoantibodies achr
Dismissed response after stimulation
Extraocualr msucles-drooping eyes double vision
More focal involvement if ab to muscle specific tyrosine kinase
Treat myasthenia gravis
Plasmapheresis and immunosuppressive
Thymectomy
Lambert Eaton
Ab presynaptic ca channel
Scc
Repetitive stimulation increases msucle response
Damage to skeletal muscle
Small pool of stem cells=satellite cells
Neurogenic disease skeletal muscle
Fiber type grouping, group atrophy
Dermatomyositis
Perifascular atropy
Prolonged corticosteroid and disuse
Type II fiber atrophy sparing type I fibers
Segmental myofiber degeneration and regeneration
Release into blood CK-muscle damage marker
Regenerating fibers rich in RNA=basophils staining, enlarged nuclei and prominent nucleoli randomly distributed in cytoplasm
Myofiber hypertrophy
Adaptation to exercise of chronic Myopathies conditions
Cytoplasmic inclusion
Vacuoles, aggregates of proteins or clusters of organelles
Mitochondrial Myopathies
Myopathies associated with inborn errors in metabolism
Arthrogryposis floppy baby
Congenital myopathies
Malignant hyperpyrexia (hypermetabolic state, triggered by anesthetics
Ion channel myopathies
3 types of inflammatory myopathies
Infectious, noninfectious inflammatory, and systemic inflammatory
Non infectious inflammatory myopathies
Dermatomyositis, polymyositis, inclusion body myositis
Dermatomyositis
Lilac of heliotrope discoloration of upper eyelids with periorbital edema -telangiectasia, nail fold, eyelids and gums
Grottos lesion
Proximal msucles first dysphagia, interstitial lung disease, cardiac involvement
Anti Mi2, antijo1, anti-155/-140
Skin changes dermatomyositis
Increase risk visceral cancer
-malignancy
Perifascular atrophy
Polymyositis
Myalgia and weakness, no cutaneous
Symmetrical proximal muscle involvment
Lacks cutaneous
Endomysial
Random distribution of affected fibers
Inclusion body myositis
Slowly progressice
Distal msucles esp extensors of knee and flexors of wrist ; asymmetric
Dysphagia
Rimmed vacuoles
Treat inflammatory myopathies
Corticosteroids
Immunosuppressive drugs
Responds poorly to immunosuppression-inclusion body
Statins
Toxic myopathies: atorvastatin, simvastatin, pravastatin
Chloroquine and hydrocychloroquine
Toxic myopathies
Original antimalarial
For symmetric autoimmune
Drug induced lysosomal storage myopathy
Slowly progressive muscle weakness TYPE 1 fiber
Ok
ICU myopathy
Aka myosin deficit myopathy
Critical illness with corticosteroid tax profound weakness affects clincila course
Thrytoxic myopathy
Acute or chronic proximal muscle weakness
Exophthalmos opthamopledia: swelling of eyelids, edema conjunctiva and diplopia
Hypothyroidism: cramping or aching decrease movement slowed reflexes
Alcohol
Toxic myopathy
Binge drinking may produce rhabdomyolisis, myoglobinuria and renal failrue acute myalgia
Congenital myopathies
Presents in infancy with muscle defects that tend to by static or to improve over time
Muscular dystrophies
Progressice msucle damage sx after infancy
Congenital dystrophies end to Present in infancy, often associated with developmental abnormalities of CNS as well as progressive msucle damage-conditions with defects in extracellular matrix surrounding myofibers
Conditions with abnormalities in receipts for extracellular matrix
Muscular dystrophies
X linked muscular dystrophy
Duchenne
Becker
Muscular dystrophy
Xp21 dystrophin
Duchess: before 5
Becker late in childhood adolescence; nearly normal lifespan cardiac dz
DMD vs BMD
No dystrophin
Decrease amount
Pseudohypertrophy
Enlargement of muscles of lower leg associated with weakness; increase bulk due to increase size of msucle fibers initially; end increase fat and connective tissue
DMD histo
Ok
Myotonic dystrophy
Kyoto is : sustained involuntary contractio of a group of msucles; can be elicited by percussion on thenar eminence
Stiff
CTG repeat expansion in DMPK
Gait, atrophy facial muscles-ptosis, hatchet face frontal balding, cataracts, cardiomyopathy
Emery Dreyfus muscular dystrophy
Mutations in genes that encode nuclear lamina proteins
Triad: slowly progressive humeroperoneal weakness, cardiomyopathy associated with conduction defects, and early contractures of Achilles’ tendon, spine, and elbows
X linked form EMD1 and AD EMD2
Carnitine palmitoyltransferase II def
Most common disease of lipid of glycogen metabolism ; episodic muscle damage with exercise and fasting
McArdle Dz
Myophosphorylase def: glycogen storage disease; episodic muscle damage with exercise
POMPE dz
Generalized glycogenesis of infancy
Acid Maltese defiency: mild in adult with respiratory and trunk muscles
Mitochondrial myopathies
Weakness, increase serum CK or rhabdomloisis
Extraocular msucle involvement commonly seen
Chronic progressive external ophthalmoplegia common in mitochondria
Lever
Point mutation mitochondrial myopathy
Leigh and barth
Mitochondrial myopathies genes encoded by nuclear DNA
Leigh-subacute necrotizing encephalopathy
Barth-infantile x linked cardioskeletal myopathy
Kearny’s sayer syndrome
Deletions or duplications of mtDNA
Weakness of extraocular muscles ophthalmoplegia
Mitochondrial myopathy
Ragged red fibers
Mitochondrial
Red trichrome stain
Spinal muscular atrophy
Spneuropathic disorder , loss of motor neurons, muscle weakness and atrophy
Infants with neurologic or neuromuscular disease may present with
Generalized hypotonia floppy infant
Infant hypotonic
Neuropathies: spinal muscular atrophy is a prosthetic example
Spinal muscular atrophy (infantile motor neuron disease
Destroys anterior horn cells
SMN1 chromosome 5
We Ig hoffman in type 1: onset at birth, floppy Abby death by 3
Muscle weakness of the truncated and extremity muscles initially followed by chewing swallowing and breathing difficulties
Histo SMA
Round atrophic fibers and innervated hypertrophied fibers
RYR1 mutation: malignant hyperthermia
Hypermetabolic state(tachycardia, tachypnea, msucle spasm, hyperpyrexia)
Can be triggered by anesthetics; halogenated inhalation agents
Anesthetic triggers increase efflux of ca from SR reticulum->tetany and excessive heat production
Central core disease AD
RYR1 gene 19q13.1
Malignant hyperthermia
NF1 brain tumor syndromes
Lesion of optic pathway glioma
Cafe at lair spots
Lisch nodules
17q11 NF1 neurofibromin
NF2
Bl acoustic schwannomas
NF2 plaque
22q12
Merlin protein
Retinoblastoma
Pineoblastoma (trilateral retinoblastoma)
Leukokoria
13q14, rb1
Von nipple Linda’s
Hemangioblastomas of the cerebellum spine
Retinal angiomatosis
3p25
Tuberous sclerosis
Subependymal giant cell astrocytoma
Ash leaf spots
Retinal astrocytoma
9q34
TSC1
Hamartin
Nevoid basal cell carcinoma gorlin syndrome
Medulloblastoma
Basal cell carcinoma
9q22.3
APC
Lhermitte duclos/crowded
Dysplastic ganglioctoma of the cerebellum
Facial trichilemmoma
10q23.3 cowden
TPEN
Li fraumeni
Malignant glioma
17q between exon5
P53
Cowden
AD
10q23
PTEN
Lipid phosphatase/benign follicular appendage tumors l internal adenocarcinoma (often breast or endometrial)
NF1
AD 17q11 NF1/neurofibromin
Negatitively regulates RAS signaling/neurofibromas
NF2
AD 22q12
NF2/merlin
Integrates cytoskeleton signaling/neurofibromas and acoustic neuromas
Tuberous sclerosis
AD
9q34 16p13
TSC1/hamartin TSC2/tbuerin
Work together in a complex that negatively regulates mTOR angiofibroma/mental retardation
Tuberous sclerosis
Hamartomas: cortical tubers, subependymal nodules
Shagreen patches
Ash leaf patches
VHL
AD polycythemia
Hemangioblastomas of cerebellum and retina
Cysts of pancreas, liver and kidneys, RCC, pheochromocytoma
NF1
Neurofibromas of peripheral nerves
Optic nerve gliomas
Lisch nodules : pigmented nodules of the iris
Cafe at lair spots: hyperpigmented cutaneous nodules
NF2
Less common
Bl schwannomas in CNVIII cerebellopontine angle increased meningiomas ependymomas
Peripheral nerve sheath tumors
Schwannomas, neurofibromas MPNST , neurofibromatosis
Schwannoma
Cerebellar pontine angle
Acoustic neuroma=CNVIII, tinnitus and hearing loss
NF2: loss of Merlin
Antoni A-spindle cells, verocay bodies-laisading nuclei around nuclear free zones
Antoni B -hypocellualr, myxoid extracellular matrix
Neurofibroma
NF1
Superficial cutaneous neurofibromas
Diffuse neurofibromas
Bag of worms malignant transformation to MPNST possible -plexiform neurofibroma
MPNST
85% HG tumors 1/2 arise for NF1 pts
SubtypeL triton tumorL rhabdomyoblastic differentiation
VHL
Regulate cell cycle control, mRNA stability and activity of HIF
Hemangioblastomas of CNS and retinae
CCRC
Pheochromocytoma
Paraneoplastic
NF1
Suppressor expression of neurofibromin
Neurofibriomin is homologous of proteins activating GTP are dependent p21 Ras. It’s importance lies int he tumor suppressing by regulating the activation fo ras dependent signal
Cafe at lait, neurofibromas, axillary or inguinal freckling, optic glioma, retinal lisch nodules
