9. PATH- Peripheral Nervous System and Skeletal Muscle

Question 1

What consists of the following: lower motor neuron with anterior horn of the spinal cord or cranial nerve motor nucleus in the brain stem, axon and muscle fibers innervated by the neuron?

Answer 1

Motor unit

Question 2

A peripheral nerve principle structural unit is the nerve fiber which is axon with its schwann cells and myelin sheath. What are numerous fibers grouped into fascicles by connective tissue sheaths?

Answer 2

Nerves

Question 3

Fascicles contain both myelinated and unmyelinated nerve fibers- unmyelinated axons are more numerous than myelinated, the cytoplasm of 1 schwann cell envelopes a variable number of unmyelinated fibers (5-10 axons). PNS axons are myelinated in SEGMENTS (internodes) separated by nodes of ranvier, single schwann cell supplies myelin sheath for?

Answer 3

each internode

Question 4

Epineurium encloses the entire nerve, perineurium is multilayered, concentric connective tissue sheath that encloses each fascicle, and what surrounds each individual nerve fiber?

Answer 4

Endoneurium

Question 5

Reactions of the motor units include segmental demyelination, axonal degeneration and muscle fiber atrophy, nerve regeneration and reinnervation of muscle, and reactions of muscle fibers. In neuromuscular disease you see a symptom of weakness and it is usually due to disorder of the?

Answer 5

Motor unit

Question 6

There are 2 main responses of peripheral nerve to injury determined by their target: 1) schwann cell damage leads to segmental demyelination with primary involvement of schwann cell and loss of myelin (just one cell/node), 2) axon damage causes axonal degeneration meaning primary involvement of neuron and its axon followed by axonal regeneration and?

Answer 6

Reinnervation of muscle

Question 7

There are two principle pathologic processes seen in muscle- 1) denervation atrophy which follows loss of axon and 2) what, which is primary abnormality of muscle fiber itself?

Answer 7

Myopathy

Question 8

In normal motor units, type I and type II myofibers are arranged in a “checker*board” distribution, and the internodes along the motor axons are uniform in thickness and length.Acute axonal injury (left axon) results in degeneration of the distal axon and its associated myelin sheath, with *atrophy of denervated myofibers. In contrast, acute demyelinating disease (right axon) produces random segmental degeneration of individual myelin internodes, while *sparing the axons.C,Regeneration of axons after injury (left axon) allows reinnervation of myofibers. The regenerated axon is myelinated by proliferating Schwann cells, but the new internodes are?

Answer 8

**shorter and the myelin sheaths are **thinner than the original ones.

Question 9

What occurs when dysfunction of schwann cell (hereditary or sensory) d/t damage to the myelin sheath like in guillain-barre, there is no primary axon abnl, does not* affect all schwann cells, and disintegrating myelin are engulfed by schwann cells and then mø?

Answer 9

Segmental Demyelination

axon AND myocytes remain intact

Question 10

The denuded axon in segmental demyelination is the stimulus for remyelination, precursor cells inside endoneurium have the capacity to replace injured schwann cells, newly myelinated internodes are SHORTER than normal, what are seen and are concentric layers of schwann cytoplasm and redundant basement membrane surrounding thinly myelinated axon?

Answer 10

Onion bulbs (schwann cell prolif where schwann wraps around an axon)

Question 11

With axonal degeneration, on EM one can see degenerating myelin with loosened myelin layers in the degenerating axon, in addition what can be seen as vacuoles derived from degenerating myelin /mø?

Answer 11

Lipid droplets

Question 12

What is a failure of outgrowing axons to find their distal target, can produce this, a non-neoplastic haphazard whorled proliferation of axonal processes and schwann cells, painful nodule that can happen when the transected ends of a peripheral nerve fail to be united after zon outgrowth?

Answer 12

Traumatic Neuroma

Question 13

Axonal degeneration is the result of destruction of the axon with secondary disintegration of the myelin sheath, what is focal or generalized trauma/ischemia affecting the whole neuron body (neuronopathy) or its axon (axonopathy)?

Answer 13

Axon damage

Question 14

In a focal lesion (traumatic transection of axon) the distal portion undergoes what, which is a prototypical pattern of injury in which the axons go in every direction?

Answer 14

Wallerian Degeneration

Question 15

IN axonal degen and muscle fiber atrophy, schwann cells catabolize myelin and later engulf axon fragments, producing small oval compartments known as what? which then after mø are recruited for clean up- proximal stump of severed nerve shows degen changes in distal most 2-3 internodes, then undergoes regeneration?

Answer 15

Myelin Ovoids

Question 16

Axonal degeneration leads to muscle fibers in the motor unit to lose neural input and undergo denervation atrophy, may see target fibers which are rounded zone of disorganized myofibers in CENTER of fiber, and what which are atrophic fibers- smaller and triangular* shap when denervation atrophy occurs?

Answer 16

Angulated Fibers = triangular shaped

Question 17

Schwann cells vacated by degenerating axons provide guide for growth cone of regenerating fibers, a regenerating cluster is a closely aggregated, thinly myelinated small-caliber group of axons, reinnervation of skeletal m changes its composition* altering the checker board distribution of the 2 major fiber types, fiber type is determined by neuron of the motor unit, WHAT determines fiber type?

Answer 17

Motor Neuron - all muscle fibers of a single unit are the SAME type

-slow growth at 1mm/day- marrow stromal cell transplants can help

Question 18

Axonal degeneration: The axon and its myelin sheath undergo anterograde degeneration (shown for the green neuron), with resulting denervation atrophy of the myocytes within its motor unit (pale-pink myocytes). Reinnervation of muscle: *Sprouting of adjacent (red) uninjured motor axons leads to fiber type grouping of myocytes, while the injured axon attempts axonal sprouting. What is known as the following: Scattered myocytes of adjacent motor units are small (degenerated or regenerated), whereas the neurons and nerve fibers are normal.

Answer 18

Myopathy

Question 19

What type of fiber?
Action: sustained force
Strength: weight bearing
Lipids: abundant
Glycogen: scant
Phys: slow twitch
Color: red

Answer 19

Type 1 - high in myoglobin and oxidative enzymes and MANY mT = tonic contractions

ONE SLOW FAT RED OX

Question 20

What type of fiber?
Action: Sudden movements
Strength: purposeful motion
Lipids: scant
Glycogen: abundant
Phys: fast twitch
Color: white

Answer 20

Type 2- rich in glycolytic enzymes, rapid phase contractions

Question 21

Axons of unaffected neighboring motor unit extend sprouts to reinnervate the denervated myocytes and incorporate them into the healthy motor unit, newly adopted reinnervated fibers assume *fiber type of their new *sibilings, what is a patch of contiguous myocytes having the same histochemical type?

Answer 21

Type grouping (as seen after axon damage and neighboring axon takes over dead axon’s muscles)

Question 22

Group atrophy is when type group becomes denervated, what type fiber atrophy occurs due to *inactivity or disuseor neurodegenerative disease, and also occurs during glucocorticoid therapy- known as steroid myopathy, NOT trauma?

Answer 22

Type 2 fiber atrophy

Question 23

Many diseases affect muscle, but myocytes only have a few pathologic reactions. What is destruction of a portion of myocyte, followed by myophagocytosis (mø infiltrate region) loss of muscle fiber leads to deposition of collagen and fat?

Answer 23

Segmental necrosis

Question 24

Along with segmental necrosis, vacuolization, alterations in structural proteins or organelles and accumulation of intraxytoplasmic deposits are seen in many disease, along with regerenation and what, which is muscle fiber splitting?

Answer 24

Hypertrophy

Question 25

What occurs via satellite precursor cells proliferate and reconstitute the destroyed portion of fiber, regenerating portion has larger internalized (Central) nuclei- should be at periphery- with prominent nucleoli, cytoplasm laden with RNA is RED (trichome stain)?

Answer 25

Muscle fiber regeneration

Question 26

Hypertrophy is a response to increase in load, either through exercise or pathologic conditions (fibers injured), what then occurs and is when large fibers may divide longitudinally, on cross section you see single large fiber with a cell membrane traversing its diameter, often with adjacent nuclei?

Answer 26

Muscle Fiber Splitting

Question 27

Patients with peripheral neuropathy (PN) generally describe the pain as tingling, stabbing, burning or pins and needles. What type affects a single nerve, with deficits in a restricted distribution, due to trauma, entrapment infections, etc?

Answer 27

Mononeuropathies

Question 28

Polyneuropathy affects many nerves, and is usually symmetric, deficits start at the feet and ascend with disease progression, hands usually have deficits at the same time as the knees = stocking and glove distribution. What damages several nerves in a *haphazard fashion, such as pt with right wrist drop and left foot drop, usually due to vasculitis commonly seen in PAN-polyarteritis nodosum?

Answer 28

Mononeuritis Multiplex

PAN: Patients usually present with asymmetric peripheral neuropathy, such asmultiple mononeuropathy(mononeuritis multiplex) with signs of motor and sensory involvement of the peroneal, median, or ulnar nerves. As additional nerve branches are affected, patients may appear to have a distal symmetric polyneuropathy.

Question 29

What neuropathy affects nerve roots as well as peripheral nerves, causing diffuse, symmetric signs and symptoms in proximal and distal parts of the body?

Answer 29

Polyradiculoneuropathies

Question 30

What mononeuropathy causes facial muscle paralysis in 15-60s, usually resolves spontaneoously, assoc with URI or DM, sx include facial tingling, mid severe headache/neck pain, balance issues, ipsilateral limb paresthesias and weakness, and sense of clumsiness… Ddx includes stroke, brain tumor, lyme disease and ramsay hunt syndrome?

Answer 30

CN VII Bell’s Palsy, usually unilateral

*Ramsay Hunt syndrome is defined as an acute peripheral facial neuropathy associated with erythematous vesicular rash of the skin of the ear canal, auricle (also termed herpes zoster oticus), and/or mucous membrane of the oropharynx.

Question 31

Neurogenic bladder (over/underactive) is a number of urinary conditions in people who lack bladder control due to a brain, SC, or nerve problem. Nerve damage can be a result of MS, parkinsons or diabetes*, can also be due to infection of brain/SC, stroke or people who are born with problems in the SC such as?

Answer 31

Spina Bifida

Question 32

What is an acute inflammatory demyelinating* polyneuropathy, life threatening, weakness begins in distal limbs and ascendings with paralysis, deep tendon reflex disappear, there is inflam and demyelination of spinal nerve roots and peripheral nerves (radiculoneuropathy) and is an acute onset immune mediated neuropathy that is treatable?

Answer 32

Guillain-Barre Syndrome

Question 33

2/3 of Guillain-Barre Syndrome preceded by acute influenza-like illness, most commonly campylobacter jejuni, cytomegalovirus, EBV, mycoplasma penumoniae or prior vaccination, can see perivenular and endoneurial infiltration by lymps, mø and plasma cells in peripheral nerves, see segmental demyelination = primary lesion what what abs?

Answer 33

Anti-Myelin antibodies

Question 34

Guillain-Barre Syndrome has cytoplasmic processes of mø that penetrate the basement membrane of schwann cells - near nodes of ranvier, and extend between myelin lamellae, stripping myelin sheath from axon, CSF see increased protein, no pleocytosis (because inflam cells are confined to roots) , what are the two treatments for this syndrome?

Answer 34

*Plasmapheresis and then IViG (if no access)

2-5% mortality from 25% due to improved respiratory care and support (most died from respiratory paralysis)

Question 35

What is the MC acquired inflammatory peripheral neuropathy assoc w symmetrical mixed sensorimotor polyneuropathy which persists for >2months, may be seen with relapses and remissions, tx with immunosuppressive (glucocorticoid, IViG, plasmapheresis), DDX: time course and RESPONDS to steroids (GB does not), see complement- IgG and IgM on myelin sheath, and sural nerve bx shows ONION BULBS?

Answer 35

Chronic Inflammatory demyelinating Poly(radiculo)neuropathy

Question 36

What disease causes invasion of schwann cells by mycobacterium, bacteria proliferates and infects other cells, see segmental demyelination and remyelination and loss of both myelinated and unmyelinated axons, endoneurial fibrosis and multilayered thickening of perineural sheaths*, with symmetric polyneuropathy affecting COOL extremities (extensors and hand/feet)?

Answer 36

Lepromatous Leprosy (Hansen Disease) = Mycobacterium Leprae= Th2 humoral response

Acid fast staining with slender bacilli, stained + for AFP*** = leprosy

Question 37

Leprosy involves pain fibers and loss of sensation contibutes to injury, there are large traumatic ulcers because patient is unaware, what kind of faces is seen?

Answer 37

Leonine Facies

Question 38

What type of leprosy is Th1 cell mediated, less severe cutaneous than other form, seen with granulomatous nodules in the dermis, localized* nerve involvement, injures cutaneous nerves, axons schwann cells and myelin is lost and there is fibrosis of perineurium and endoneurium?

Answer 38

Tuberculoid Leprosy

Question 39

What has an exotoxin that affects peripheral nerves and begins with paresthesias and weakness- imcomplete immunization and waning adult immunity is why its caused, early loss of proprioception and vibratory sensation due to 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 muscle dysfunction causing death?

Answer 39

Diptheria

Question 40

What is the MC viral infection of the PNS, latent infection of sensory ganglia of the SC and brainstem in dorsal root ganglia, reactivation of latent infection causes painful vesicular skin eruption in distribution of sensory dermatomes= shingles, neuronal destruction and loss of affected ganglia?

Answer 40

Varicella-Zoster Virus

Question 41

Varicella-Zoster Virus shows abudant mononuclear infiltrate, regional necrosis and hemorrhage may also be found, axon degeneration of peripheral nerves after death of sensory neurons is seen, focal destruction of large motor neurons in the anterior horn or what may be seen at corresponding levels?

Answer 41

cranial nerve motor nuclei

Question 42

What is assoc with various neurologic manifefstations occuring in the 2nd and 3rd stage of the disease including polyradiculoneuropathy, unilateral or bilateral facial nerve palsies and is spread via ticks and is associated with erythema chronica migrans?

Answer 42

Lyme Dz due to B. Borgurllai

Question 43

What virus causes mononeuritis multiplex, a demyelinating DO that resembles Guillain barre or chronic inflam demyelinating polyneuropathy, and in late stages of the virus can see distal sensory neuropathy which is painful?

Answer 43

HIV

Question 44

What is the MCC of peripheral neuropathy, MC pattern is ascending distal symmetric sensorimotor polyneuropathy, prevalence of complications depends on the duration, with >15 years with disease =80%, see numbness, loss of pain sensation, difficulty with balance, paresthesias and dysesthesias (pain), neuropathy leads to chronic skin ulcers and diffuse vascular injury?

Answer 44

Diabetes Mellitus

Question 45

Diabetes Mellitus is associated with segmental demyelination with a DEC in axons, degen of myelin sheaths and regenerative axonal clusters, relative loss of small myelinated and unmyelinated fibers, large fibers are also affected, endoneurial arterioles show thickening, hyalinization and intense?

Answer 45

PAS positivity

Question 46

Diabetes Mellitus is also associated with dysfunction of autonomic nervous system in 40% almost always assoc with distal sensorimotor neuropathy, sx include postural hypotension, incomplete emptying of bladder, increased infections and sexual dysfunction, on EM see thickening of endoneurial vessel wall, marked loss of myelinated fibers and?

Answer 46

thinly myelinated fibers

Question 47

What ocurrs in most people with renal failure have periph neuropathy, showing distal symmetric neuropathy- may be asymptomatic, muscle cramps, distal dysesthesias and dec in DTRs, axonal degeneration usually primary even, regeneration and recover common after dialysis?

Answer 47

UREMIC Neuropathy

Question 48

What dysfunction can cause compression mononeuropathies such as carpel tunnel, distal symmetrical predominantly sensory polyneuropathy?

Answer 48

Thyroid Dysfunction (hypothyroid)
Hyperthyroid rarely causes guillain barre

Question 49

What deficiency causes subacte combine degeneration with damage to long tracts in the spinal cord and peripheral nerves?

Answer 49

VitB12 cyanocobalamin

Question 50

Peripheral neuropathies may appear afterexposure to industrial or environmental chemicals, biologic toxins, or therapeutic drugs.Important causes of toxic peripheral nerve damage include alcohol (independent of associated nutritional deficiencies), heavy metals (lead, mercury, arsenic, and thallium), and organic solvents. Various medications can cause toxic nerve damage, but the most notorious are what? These include vinca alkaloids and taxanes, microtubule inhibitors that interfere with axonal transport, and cisplatin, which may cause a neuronopathy.

Answer 50

chemotherapeutic agents

Question 51

Neuropathies from local effects of malignancy, complications of its treatment, paraneoplastic effects or tumor derived Ig (B cell tumors). Direct infiltration of compression of peripheral n. can cause obturator palsy (pelvic tumor) or what from neoplasms of the apex of the lung?

Answer 51

Brachial Plexopathy

Question 52

Neuropathies associated with monoclonal gammopathies (b-cell neoplasms), POEMS syndrome is common: polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes, deposition of paraprotein between noncompacted myelin lamellae is seen, What paraneoplastic neuropathy is the MC and causes sensorimotor neuronopathy, which is distal, asymmetric and multifocal?

Answer 52

Small Cell Lung Carcinoma

Question 53

What type of neuropathy regenerates slowly and discontunity complicates its regrowth, axons continue to grow despite misalignment resulting in small bundles of axons randomly oriented but surrounded by organized layers of scwann cells, fibroblasts and perineural cells intermixed with connective tissue?

Answer 53

Traumatic Neuroma

Question 54

In carpel tunnel syndrome, what nerve is compressed in the transverse carpal ligament seen frequently in women bilaterally, causes numbness and paresthesias at tip of thumb and first 2 digits, associated with tissue edema, pregnancy, inflammatory arthritis, hypothyroidism, amyloidosis, acromegaly, diabetes, and excessive repetitive motions?

Answer 54

Median N

Question 55

Saturday night palsy is caused by compression of what nerve in the upper arm when one falls asleep awkwardly? other compression neuropathy is ulnar N at elbow and peroneal nerve at knee…

Answer 55

Radial nerve

Question 56

What nueroma causes metatarsalgia (foot pain), histologically the lesion has perineural fibrosis usually at interdigital nerve at intermetatarsal sites, MC in Women?

Answer 56

Morton Neuroma

Question 57

Inherited peripheral neuropathies are uncommon- must be considered in DDx of anyone presenting with peripheral neuropathy. What is the MC inherited PN, MC d/t AD chr 17, PMP22 mutation peripheral myelin protein22, in second decade of life, slowly progressive demyelination of motor and senosry nerves (also Xlinked and AD-MDN2 associated with early childhood onset)?

Answer 57

Charcot-Marie-Tooth CMT assoc with distal muscle atrophy, sensory loss and foot deformities + onion bulb formation

Question 58

What is a hereditary polyneuropathy that is due to deposition of amyloid in peripheral nerves, due to germline mutation of transthyretin gene?

Answer 58

Familial Amyloid Polyneuropathy

Question 59

Upon depolarization, presynaptic nerve terminals release acetylcholinesterase (ACh) into the synaptic cleft, AChR are responsible for initiation of signals leading to muscle contraction, regardless of the cause, DOs that impair function of the NM juction tend to be present with painless weakness**, either due to inherited defects, toxins or antibody mediated like myasthenia gravis (antib to AChR) and?

Answer 59

Lamber-Eaton Myasthenic Syndrome

Question 60

What NMJ disease is common, with a bimodal age, more common in women, and in older adults mc in men, there is immune mediated loss of acetylcholine receptors (85%) have circulation Ab to AChR, remaining have Ab against sarcolemmal protein muscle specific receptor tyrosine kinase, with a strong association between AChR and thymic abnormalities**?

Answer 60

Myasthenia Gravis

Question 61

Myasthenia Gravis is associated with a b9 thyroid tumor called a thymoma, and 30% of patients with MG have what, which is MC in younger and histo shows B cell follicles in the thymus possibly due to hyperplasia disrupting normal thymic function which promotes autoimmunity against AChRs expressed on thymic myoid cells?

Answer 61

Thymic Hyperplasia

Question 62

Myasthenia Gravis is d/t autoabs at AChRs at NMJ, pts present with fluctuating generalized weakness that worsens with exertion and over the course of the day, weakness begins with extraocular muscles- dropping eyelides (ptosis) and double vision (diplopia), there is characteristic diminshed responses after?

Answer 62

repeated stimulation

Question 63

Myasthenia Gravis is treated with acetylcholinesterase inhibitors which increases the half life of ACH, a thymectomy may be performed for those with a thymoma which may benefit overall disease, and immunosupressives and what are the other option for treatment, to decrease the amount of autoabs?

Answer 63

Plasmapheresis

*neostigmine

Question 64

What syndrome is assoc with ab that block acetylcholine release by inhibiting presynaptic calcium channels, is is usually a paraneoplastic process, 50% are associated with small cell carcinoma of the lung*, sx may precede diagnosis of cancer by years, causes proximal muscle weakness and autonomic dysfunction, repeptitive stimulation INCREASES muscle response which is opposite of MG?

Answer 64

Lambert Eaton Myasthenic Syndrome

Question 65

Skeletal muscle myofibers are arranged in fascicles each associated with a small pool of tissue stem cells which are what cells which contribute to muscle regeneration? myofibers are two main types- 1 and 2 and are admixed in checkerboard fashion, fiber type determined by signals received from innervating motor neurons

Answer 65

Satellite Cells**

Question 66

Type 1 muscle has sustained force, aerobic exercise, low power, high resistance to fatigue, stains red due to high myoglobin and prottype is soleus (pigeon), type 2 fibers are for fast movement, anaerobic exercise, high power, low resistance to fatigue*, stains pale red tan (low myoglobin) and protype is what?

Answer 66

Pectroal (pigeon)

Question 67

Curare is a muscle relaxant that blocks acetycholine receptors causing flaccid paralysis, what is a neurotoxin produced by clostridium botulinum which blocks release of ach from presynaptic neurons?

Answer 67

Botulism

Question 68

Skeletal muscle atrophy is a common feature of many DOS, causes include loss of innervation, disuse, cachexia, old age and primary myopathies, severe atrophy may lead to loss* of muscle mass, neurogenic disease causes fiber type grouping and group atrophy, what is common and causes perifascicular atrophy?

Answer 68

Dermatomyositis

Note: prolonged corticosteroid tx and disuse leads to TYPE 2*** fiber atrophy and type 1 fibers are spared

Question 69

SKM DOs may be via myopathic or neurogenic injury… segmental myofiber degeneration and regeneration causes release of creatine kinase CK** into blood which is a marker for muscle damage, regenerating fibers are rich in RNA so they stain how, with enlarged nuclei, with prominent nucleoli randomly distributed in the cytoplasm?

Answer 69

RNA stains Basophilic on HandE

Question 70

Myofiber hypertrophy is due to adaptation to exercise or chronic myopathic conditions, cytoplasmic inclusions may be seen, including vacuoles, aggregates of proteins or clusters of?

Answer 70

organelles

Question 71

There are 3 types of inflammatory myopathies, including infectious, noninfectious inflammatory and systemic inflammatory, noninfectious inflammatory myopathies include polymyositis, inclusion body myositis and what, which is the most common and see skin and muscle changes?

Answer 71

Dermatomyositis

Biopsy shows deposition of complement MAC (C5b-9) in capillary beds of muscles and skin

Question 72

Dermatomyositis is seen in 4-6th decade, associated with a distinctive skin rash- lilac or heliotrope (purple) discoloration of upper eyelides assoc with periorbital edema, also see telangiestasias (dilated capillary loops) on nail folds, eyelids and gums, what lesions are seen which are scaling erythematous eruptionor dusky patches over knuckles, elbows and knees?

Answer 72

Grotton lesions

Question 73

Dermatomyositis sx include proximal muscles first (difficulty rising from chair or climbing stairs), 1/3 dev dysphagia (oropharyngeeal and esophageal m), 10% interstitial lung disease, cardiac involvement is common but rarely causes cardiac failure, Auto antibodies associated with this disease includ anti-Jo1 (mechanics hand), anti-P155/P140 (paraneoplastic and juvenile) and what which is the most common?

Answer 73

Anti Mi2 (heliotrope rash and grotten papules)

Question 74

Dermatomyositis increases risk of visceral cancer, 25% of adults with Dermatomyositis have an associated malignancy (paraneoplastic?), histo will show what, which is atrophic fibers grouped at the periphery of fascicles with mononuclear infiltrate in perimysial connective tissue?

Answer 74

Perifascicular Atrophy

Muscle bx- perimysial aggregates of mononuclear inflammatory cells and perifascicular atrophy

Question 75

What type of dermatomyositis which has an avg age onset at 7 y/o, is the MC myopathy in children, inolves the GI tract (mucosal ulcers ,perforation), calcinosis and lipodystrophy (vs heart, lung or underlying malignancy in adults)?

Answer 75

Juvenile Dermatomyositis

Question 76

What has an adult onset, with myalgia and weakness, with NO cutaneous features and is a dx of exclusion, with *symmetrical proximal muscle involvement and may have inflamm involvement of heart and lungs and autoAbs, due to CD8 T cells in endomysium, necrotic and regerating fibers scattered through out fascicle with endomysial mononuclear infiltrate, random distribution of affected fibers?

Answer 76

Polymyositis

Question 77

What myositis which is a dz of late adulthood, greater than 50 yo, MC inflammatory myopathy in patients greater than 65, slowly progressive muscle weakness, most severe in quadriceps and distal upper extremities, starts with DISTAL muscles- esp extensors of knee and flexors of wrist and fingers *asymmetric, with dysphagia from esophageal and pharyngeal m involvement?

Answer 77

Inclusion Body Myositis

Question 78

Inclusion Body Myositis on histo shows rimmed vacuoles (inclusion with reddish granular rimming- purpleish) highlight by basophilic granules around the periphery, endomysial fibrosis, what kind of stain shows this?

Answer 78

Gomori Trichrome

Question 79

Treatment of inflammatory myopathies- prior to corticosteroids, prognosis for dermatomyositis and polymyositis was poor (mortality of 50%). Immunosupressive drugs are used if what (which is first line tx)? (third line tx is IViG, cyclophosphamide, cyclosporine, rituximab, inclusion body myositis usually responds POORLY to steroids….

Answer 79

CORTICOSTEROIDS ARE FIRST LINE

Question 80

Toxic myopathies can be caused by prescription or recreation drugs and hormonal imbalances. What such as atrorvastatin, simvastatin, and pravastatin can cause myopathy, 1.5% of users feel this?

Answer 80

Statin drugs

Question 81

Chloroquine and hydroxychloroquine are antimalarial drugs can cause toxic myopathies, now used as long term tx for systemic autoimmune dzs, drug induced lysosomal storage myopathy, causes slowly progressive muscle weakness, type 1 fibers are affected**, ICU myopathy is AKA myosin deficit myopathy associated with critical illness with corticosteroid tx- profound weakness. What causes acute or chronic proximal muscle weakness associated with exophthalamic opthalmoplegia -swelling of eyelids edema conjuctiva and diplopia?

Answer 81

Thyrotoxic Myopathy

Question 82

NOTE: alcohol may produce rhabdomyolysis, myoglobinuria, and renal failure with acute myalgia
NOTE: x linked dominant - 100% daughters are affected from father
X linked recessive- 100% sons affected via positive mom

Answer 82

WOOF

Question 83

Congenital myopathies may present in infancy with muscle defects that tend to be static or to improve over time. What inherited diseases of SKM cause progressive muscle damage with sx occuring after infancy*, congenital dystrophies tend to present in infancy, often assoc with developmental abnormalities of the CNS as well as progressive muscle damage?

Answer 83

Muscular Dystrophies

Question 84

Xlinked Muscular Dystrophies include ducenne DMD which is more common and more severe, and becker BMD is same genetic locus, other MDs include limb girdle muscular dystrophy LGMDs which are autosomal dominant or recessive and due to what complex of proteins?

Answer 84

Sarcoglyan complex of proteins

Question 85

What muscular dystrophy is due to mutation in DMD gene, Xp21, the dystrophin gene, 2/3 are familial, female carries are asymptomatic, increased creatine kinase CK is seen, risk for developing cardiomyopathy (along with affected males), most common, sx before 5y/o and wheelchair by 10-12?

Answer 85

Duchenne Muscular Dystrophy

LOF mutation- frameshift mutation

Tx: supportive

Question 86

What MD starts in late childhood adolescene and has a nearly normal lifespan with more prominent cardiac dz*, assoc with a decreased amount of dystrophin (not complete loss)?

Answer 86

Becker Muscular dystrophy

Question 87

DMD has NO dystrophin gene so effects are more widespread. Dystrophin and dystrophin associated protein complex form an interface between the intracellular contractile apparatus and extracellular connective tissue matrix (concentrated at the plasma membrane over Z bands)- has a role of transferring force of contraction to CT proposed to be basis for myocyte degeneration in absence of dystrophin. What is seen in both and is enlargement of muscles of lower leg assoc with weakness- increase bulk due to increased size of muscle fibers initially, and later due to increased fat and CT?

Answer 87

Pseudohypertrophy

Question 88

Histology of both BMD and MMD include variation in fiber size, increased number of internalized nuclei, degeneration, necrosis, and phagocytosis of muscle fibers, regen of muscle fibers, proliferation of endomysial CT, in DMD- enlarged rounded hyaline fibers that have lost their cross striations*, later stages show muscle almost totally replaced by fat and CT, so it is important to do what early?

Answer 88

EARLY biopsy - end point morphology of BMD and DMD are very similar

Question 89

Regenerating muscle fibers stain blue with large nuclei, and on histo there is complete absence of endomysial coverage, myofibers vary in size but fascicular muscle architecture is maintained, advanced disease is associated with what on bx?

Answer 89

fatty replacement and endomysial fibrosis

*IHC- absence of normal sarcolemmal staining pattern DMD and reduced in BMD

Question 90

What dystrophy is characterized by stiffness difficulty releasing grip due to sustained involuntary contraction of a group of muscles, can be elicited by percussion on thenar eminence, sx include skeletal m weakness, cataracts, endocrinopathy, and cardiomyopathy– AD mutation in CTG trinucleotide for DMPK, anticipation occurs and there are ring fibers and sarcoplasmic masses?

Answer 90

Myotonic Dystrophy- triple repeat expansion disorder

SX: weakness, contractions, SOB and edema with cardiomyopathy

CK signifcantly elevated

Question 91

Myotonic Dystrophy presents with abnl gait, then atrophy of the facial muscles causing ptosis, and hatchet face with frontal balding, cataracts and cardiomyopathy, on histo you see what which are parasite like?

Answer 91

Ring fibers

Question 92

What dystrophy is less common, mutations in genes that encode nuclear lamina proteins, traid sx - slowly progressive humeroperoneal weakness, cardiomyopathy with conduction defects and early contractures of the achilles tendon, spine and elbows, Xlinked form EMD1 and AD form is EMD2?

Answer 92

Emery Dreifuss Muscular Dystrophy

Question 93

What less common dystrophy causes muscle weakness that preferentially involves proximal muscle groups, multiple AD and AR entities, age of onset and severity of dz vary greatly?

Answer 93

Limb-Girdle Muscular Dystrophy

Question 94

Many inborn errors of lipid or glycogen metabolism affect SKM- two general patterns of muscle dystrophy include sx with exercise or fasting (severe m cramping and pain/ rhabdomyolysis), and 2) slowly progressive muscle damage. What deficiency is the MC, episodic muscle damage with exerciing and fasting due to impaired transport of free fatty acids to mitochondria?

Answer 94

Carnitine Palmitoyltransferase II Def

Question 95

McArdle Dz (myophosphorylase def.) is a glycogen storage disease with episodic muscle damage with exercise, what deficiency is has 3 types, mild is adult form, causing myopathy of respiratory and truncal muscles, and severe is generalized glycogenesis of infancy due to impaired conversion of glycogen to glucose causing accumulation of glycogen in lysosomes?

Answer 95

Acid Maltase Deficiency = POMPE dz (severe infantile form)

Question 96

mT myopathies (oxidative phosphorylation diseases) are mutations in both nucelar and mT genes, causing LACK of ATP = SKM and other tissues rich in ATP requirements are affected, sx include weakness, increase CK or rhabdomyolysis, chronic progressive external opthalmoplegia is common, and what muscle is most commonly affected due to exceptoinally atp requirement?

Answer 96

Extraocular Muscles*

Question 97

mT myopathies (oxidative phosphorylation diseases) are mutations in both nucelar and mT genes, causing LACK of ATP = SKM and other tissues rich in ATP requirements are affected, sx include weakness, increase CK or rhabdomyolysis, chronic progressive external opthalmoplegia is common, and what muscle is most commonly affected due to exceptoinally atp requirement?

Answer 97

Extraocular Muscles*

Question 98

What are aggregates of abnormal mitochondria under the sarcolemma (red on trichrome stain) causing distortion of myofibrils, and on EM shows morphologically abnormal mT with concentric membranous rings = phonograph records with rhomboid paracrystalline-parking lot*** inclusions (alterations in cristae of mT)?

Answer 98

Ragged Red Fibers = mT myopathies

Question 99

What atrophy is an AR neuropathic disorder, loss of motor neurons leading to muscle weakness and atrophy, infants with THIS neurologic or neuromuscular disease may present with generalized hypotonia which = floppy infant?

Answer 99

Spinal Muscular Atrophy SMA

Question 100

DDx for floppy infant or infantile hypotonia includes primary disease of SKM (MG), congenital myotonia, congenital myopathies, congenital muscular dystrophies, abnormalities of the brain (encephalopathy) and neuronopathies like spinal muscular atrophy which is the prototypic example, SMA is AR and seen in 1/6000 births, and destroys what part of the spinal cord?

Answer 100

Anterior horn cells

Question 101

Spinal Muscular Atrophy SMA begins in childhood or adolescence and loss of fibers begin in utero, survival motor neuron 1 SMN1** is the mutated gene (homozygous disruption), see large zones of atrophic myofibers mixed with scattered NL or hypertrophied myofiber- retain innervation. What is the MC SMA (type 1)- onset at birth with floppy baby and death at less than 3, muscle weakness of truncal extremity muscles intially, followed by chewing, swallowing and breathing difficulties?

Answer 101

Wernig Hoffman

lack motor neurons = SKM atrophy

Question 102

on histo with Spinal Muscular Atrophy SMA, there is spinal muscular atrophy with groups of round atrohpic muscle fibers or panfascicular atrophy*, resulting from denervation, what are rarely seen compared to atrophic rounded myofibrils, which are larger than those innervated and have undergone compensatory hypertrophy?

Answer 102

innervated hypertrophied myofibers

Question 103

Ion channel myopathies (channelopathies) are mutations affecting function of ion channels proteins, most are AD- symptoms include epilepsy, migraine, movement DOs with cerebellar dysfunction, peripheral N dzs, and muscle dz, inc or dec excitability causing hypo/hypertonia- hypotonia is associated with both increased, decreased or normal what?

Answer 103

serum potassium

hyperkalemic/hypokalemic/normokalemix periodic paralysis

MCC of hypokalemic paralysis is CACNA1S mutation = caclium channel mut

Question 104

What central core disease is due to a AD RYR1 (ryanodine receptor) mutation, associated with a hypermetabolic state with tachycardia, tachypnea, muscle spasms, and hyperpyrexia, can be triggered by anesthetics, usually halogenated inhalational agents, anesthetic triggers efflux of Ca from sarcoplasmic reticulum which causes tetany and excessive heat production?

Answer 104

Malignant Hyperthermia**

severe painful tetanic muscle spasms, difficulty reducing temperature

tx with dantrolene

Question 105

What disease is AD mut of chr3, tumor supressor, involved in regulating expression of erythropoietin (via VEGF) causing polycythemia, also see hemangioblastomas of cerebellum and retina, cysts of pancreas, liver and kidneys, renal cell carcinoma and pheochromocytoma?

Answer 105

VHL mutation- Von Hippel-Lindau Disease

Question 106

What disease is AD, causing seizures, autism, mental retardation, two kinds type 1 chr 9 hamartin and type 2 chr 16 tuberin, causes cortical tubers, renal angiomyolipomas, pulmonary lymphagioleiomyomatosis, cardiac rhabdomyomas, and cutaneuous lesions* = angiofibromas, subungal fibromas*, shagreen pathches of thickening and ash leaf patches of hypopigmented areas?

Answer 106

tuberous sclerosis complex (candle guttering- drop like masses bulge into the ventricles of the brain)

Question 107

NF1 type one is common AD, causing neurofibromas of peripheral nerves, optic nerve gliomas, lisch nodules of iris and cafe au lait spots = hyperpig cutaneous nodules, NF type 2 is less common AD, see increase in meningiomas* and ependymomas, and what which is very improtant?**

Answer 107

Bilateral Scwannomas - CN VIII 8 at cerebellopontine angle

Question 108

Schwannoma is a peripheral nerve sheath benign tumor that shows schwann cell differentiation, test S100+, located a the cerebellar pontine angle, acoustic neuroma is at CNVIII and causes tinnitus and hearing loss, what are comprised of dense spindle cells that contain verocay bodies which are palisading nuclei around nuclear free zones?

Answer 108

Antoni A

Antoni B is loose cells/hypocellular with myxoid extracellular matrix

(both types mixed together in schwannomas +hyalinized BVs)

Question 109

NFs are benign nerve sheath tumors that are more heterogeneous - the neoplastic schwann cells are ADMIXED with perineruical like cells, fibroblast, mast cells and CD34+ spindle cells, unlike schwannomas… NF is either sporadic or NF1 associated, associated with superficial cutaneous NFs, diffuse NFs, or plexiform neurofibroma which can malignantly transform to MPNST and feels/looks like?

Answer 109

a bag of worms (plexiform neurofribroma)

Question 110

MPNST or malignant peripheral nerve sheath tumor is an uncommon HIGH GRADE tumor, 1/2 of the HG tumors arise in NF1 patients, associated with divergent differentiation in terms of the presence of focal areas that exhibit glandular, cartilaginous, osseous, and rhabdomyoblastic morphology, this is known as?

Answer 110

Triton tumor = Rhabdomyoblastic differentiation