Hertz Muscles

Question 1

Type I vs Type II muscles

Answer 1

One slow fat red ox

I: sustained force, aerobic exercise, low power, high resistance to fatigue, high lipid content, low glycogen content, low glycolytic capacity, high oxidative capacity, high mitochondrial density

Type II: fast movement, anaerobic exercise, high power, low resistance to fatigue, low lipid content, high glycogen content,

Question 2

muscle biopsy pattern should look like

Answer 2

checkerboard- even spread of light and dark

Question 3

Skeletal Muscle Atrophy

Answer 3

Clusters or groups of atrophic fibers are seen in neurogenic disease

** Perifascicular atrophy is seen in dermatomyositis

Type II fiber atrophy with sparing of type I fibers is seen with prolonged corticosteroid therapy or disuse atrophy

Question 4

Neurogenic and Myopathic Changes in Skeletal Muscle

Answer 4

Disorders impacting skeletal muscle may do so by damaging myofibers directly (myopathic injury) or by disrupting muscle innervation (neurogenic injury). Neurogenic injuries lead to ** fiber type grouping and grouped atrophy**

Other changes: can see Segmental myofiber degeneration and regeneration, myofiber hypertrophy, or cytoplasmic inclusions

Question 5

Segmental myofiber degeneration and regeneration

Answer 5

is seen when only part of a myofiber undergoes necrosis. Degeneration is associated with release of cytoplasmic enzymes into the blood such as * creatine kinase, making these useful markers of muscle damage.

Question 6

Myofiber hypertrophy

Answer 6

physiologic adaptation to exercise or in association with certain chronic myopathic conditions.

Question 7

Cytoplasmic inclusions (muscle)

Answer 7

in the form of vacuoles, aggregates of proteins, or clustered organelles are characteristic of several primary forms of myopathy.

Question 8

Inflammatory Myopathies

Answer 8

Historically, * polymyositis, * dermatomyositis, and * inclusion body myositis have been considered the three main primary inflammatory myopathies; however, inclusion body myositis is an enigmatic condition in which the role of inflammation is uncertain.

Other immune-mediated disorders, such as systemic lupus erythematosus, systemic sclerosis, and sarcoidosis, as well as certain infectious agents, can also cause myositis

Question 9

proximal muscle weakness is what?

Answer 9

can’t get up out of a chair, e.g.

going up stairs wears out

Question 10

Dermatomyositis

Answer 10

Dermatomyositis is a systemic autoimmune disease that typically presents with * proximal muscle weakness and skin changes

Dermatomyositis is an immunologic disease in which damage to small blood vessels contributes to muscle injury

mechanic’s hands
anti Jo-1

Question 11

Autoantibodies in dermatomyositis

Answer 11

Anti-Mi2 antibodies (directed against a helicase implicated in nucleosome remodeling) show a strong association with prominent * Gottron papules and heliotrope rash.*

Anti-Jo1 antibodies (directed against the enzyme histidyl t-RNA synthetase) are associated with interstitial lung disease, nonerosive arthritis, and a skin rash described as “mechanic’s hands.”

Anti-P155/P140 antibodies (directed against several transcriptional regulators) are associated with paraneoplastic and juvenile cases of dermatomyositis.

Question 12

CREST syndrome

Answer 12

Calcinosis
Reynaud's
Esophageal dysmotility
Sclerodactyly (sausage fingers)
Telangiectasias

Question 13

dermatomyositis clinical features

Answer 13

heliotrope rash, CREST syndrome, perifascicular rash, peripheral muscle weakness- elevation in serum creatine kinase
red patches over the knuckles, elbows, knees- Gottron papules
Dysphagia
interstitial lung disease

Question 14

Polymyositis

Answer 14

adult-onset inflammatory myopathy that shares myalgia and weakness with dermatomyositis but lacks its distinctive cutaneous features

diffuse lymphocytes on mucle biopsy (spider web, not perifascicular)

CPK high

Question 15

Inclusion Body Myositis

Answer 15

Inclusion body myositis is a disease of late adulthood that typically affects patients * older than 50 years and is the most common inflammatory myopathy in patients older than age 65 years

Most affected individuals present with slowly progressive muscle weakness that tends to be most severe in the * quadriceps and the distal upper extremity muscles

• do not get better with steroids
• stuff in the middle of the muscle cells

Question 16

Treatment of Inflammatory Myopathies

Answer 16

Corticosteroids remain the first-line of treatment for polymyositis and dermatomyositis.

Immunosuppressive drugs are used in steroid-resistant disease or as steroid-sparing agents and include azathioprine and methotrexate. Intravenous immunoglobulin (IVIG), cyclophosphamide, cyclosporine, and rituximab (an antibody that targets B cells) are third-line therapies.

Inclusion body myositis usually responds poorly to steroids or immunosuppressive therapies, another feature that argues against an inflammatory or immune origin for this disorder.

Question 17

Toxic Myopathies

Answer 17

Myopathy is the most common complication of statins
Chloroquine and hydroxychloroquine (antimalarial agents)
Thyrotoxic myopathy presents most commonly as an acute or chronic proximal muscle weakness that may precede other signs of hyperthyroidism
Alcohol can also be myopathic. Most notably, binge drinking may produce an acute toxic syndrome of rhabdomyolysis, myoglobinuria, and renal failure.

Question 18

Muscular Dystrophies

Answer 18

include several inherited disorders of skeletal muscle that have in common progressive muscle damage that typically manifests itself between * childhood and adulthood

The most common muscular dystrophies are X-linked and stem from mutations that disrupt the function of a large structural protein called * dystrophin

• Duchenne and Becker muscular dystrophy are caused by loss-of-function mutations in the dystrophin gene on the X chromosome

Question 19

Becker is like bud and bud light

Answer 19

later and less severe

Duchenne’s no dystrophin
Becker a little dystrophin
normal lots of dystrophin

Question 20

clinical features of Duchenne muscular dystrophy

Answer 20

normal at birth. Very early motor milestones are met, but * walking is often delayed. The first indications of muscle weakness are clumsiness and inability to keep up with peers.

Weakness begins in the * pelvic girdle muscles and then extends to the shoulder girdle. Enlargement of the muscles of the lower leg associated with weakness, termed * pseudohypertrophy, is often present. The mean age of wheel chair dependence is around 9.5 years. Patients develop joint contractures, scoliosis, worsening respiratory reserve, and sleep hypoventilation.

• Serum creatine kinase is markedly elevated during the first decade of life due to ongoing muscle damage, and then falls as the disease progresses and muscle mass is lost. The presence of a dystrophin mutation can be confirmed by genetic studies

Question 21

Gower’s sign

Answer 21

can’t get up normally
pushing on knees to get up
classic muscular dystrophy sign

Question 22

mitochondrial myopathies- what do we see?

Answer 22

ragged red fibers at periphery of muscle fibers

young athlete

Question 23

Spinal Muscular Atrophy and the Differential Diagnosis of a Hypotonic Infant

Answer 23

Spinal muscular atrophy is a neuropathic disorder in which loss of motor neurons leads to muscle weakness and atrophy

Infants with neurologic or neuromuscular disease may present with generalized hypotonia (“floppy infant”).

ddx of hypotonia: primary diseases of skeletal muscle (e.g., congenital myasthenic syndrome, congenital myotonia, congenital myopathies, and congenital muscular dystrophies), abnormalities of the brain (e.g. encephalopathy), and neuronopathies, of which spinal muscular atrophy is a prototypic example.

Question 24

Ion Channel Myopathies (Channelopathies)

Answer 24

Symptomatic patients have elevated, depressed, or normal serum potassium levels and are called * hyperkalemic, hypokalemic, and normokalemic periodic paralysis*

linked to malignant hyperthermia

Upon exposure to anesthetic, the mutated receptor allows increased efflux of calcium from the sarcoplasmic reticulum, leading to tetany and excessive heat production.

DANTROLENE

Question 25

disorders of skeletal muscle- key concepts from robbins

Answer 25

• altered muscle function may stem from neurogenic or primary myopathic processes
• myopathic- often marked by degeneration and regeneration of myofibers

3 main inflammatory: polymyositis, dermatomyositis, inclusion body myosits

Inclusion body myositis- chronic progressive disease of older patients associated with rimmed vacuoles

Dermatomyositis- children and adults, latter often paraneoplastic. Immune damage to small blood vessels and perifascicular atrophy common features

Polymyositis- adult onset myopathy caused by CD8-T cells

Muscular dystrophies and congenital myopathies result from mutations that disrupt the function of proteins that are important for various aspects of muscle development, function, and regeneration. Some of these diseases present in infancy, others in adulthood. They may be relentlessly progressive or cause relatively static deficits.

Myopathy can result from toxic injury or be the result of metabolic diseases including those of lipid metabolism, glycogen metabolism, and mitochondria.

Question 26

Peripheral Nerve Sheath Tumors

Answer 26

The vast majority of these are composed of cells that show evidence of Schwann cell differentiation. These include the three common types, schwannoma, neurofibroma, and malignant peripheral nerve sheath tumor (MPNST)

Peripheral nerve sheath tumors have several unique features. One is their association with relatively common familial tumor syndromes, including neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwan­nomatosis

Question 27

consistent finding in all schwannomas

Answer 27

loss of merlin (NF2 gene product)

Question 28

key things to know about schwannomas

Answer 28

cellularity areas (Antoni A) and loose, pale Antoni B areas

benign

tumor cell nuclei aligned in palisading rows leaving anuclear zones and resulting in the formation of Verocay bodies

Question 29

Clinical Features

of schwannomas

Answer 29

Most Schwannomas cause symptoms by local compression of the involved nerve or adjacent structures (e.g., brainstem or spinal cord).

Within the cranial vault, most schwannomas occur at the cerebellopontine angle, where they are attached to the vestibular branch of the * eighth nerve. Affected individuals often present with *tinnitus and hearing loss; the tumor is commonly referred to as an * acoustic neuroma—a double misnomer, since the tumor neither arises from the acoustic portion of the nerve nor is it a neuroma

can also see facial weakness (facial nerve runs through there too)

Question 30

Neurofibromas

Answer 30

Neurofibromas are benign nerve sheath tumors that are more heterogeneous in composition than schwannomas. The neoplastic Schwann cells are admixed with perineurial-like cells, fibroblasts, mast cells, and CD34+ spindle cells.

• Superficial cutaneous neurofibromas often present as pedunculated nodules that can be seen isolated (if sporadic) or multiple (if NF1-associated).
• Diffuse neurofibromas often present as a large plaquelike elevation of skin and are typically NF1-associated.
• Plexiform neurofibromas can be found in deep or superficial locations in association with nerve roots or large nerves and are uniformly NF1-associated.

Question 31

Malignant Peripheral Nerve Sheath Tumors (MPNST

Answer 31

Most are high-grade

• divergent differentiation- presence of focal areas that exhibit other lines of differentiation, including glandular, cartilaginous, osseous, or rhabdomyoblastic morphology. A tumor exhibiting the latter is referred to as * Triton tumor

Question 32

kid with cafe au lait spots

Answer 32

could be Neurofibromatosis type I

100s of them - definitely

Question 33

neurofibromatosis type 2

Answer 33

This is an autosomal dominant disorder resulting in a range of tumors, most commonly * bilateral eighth-nerve schwannomas and multiple meningiomas

Question 34

peripheral nerve sheath tumors: robbins key concepts

Answer 34

3 common ones: schwannoma, neurofibroma, and malignant peripheral nerve sheath tumor- all likely arise from cells of Schwann cell lineage

Schwannomas- encapsulated benign tumors, can be associated with NF2

Neurofibromas - benign peripheral nerve sheath tumors sometimes associated with NF1, can be subtyped as localized cutaneous, diffuse, or plexiform

Malignant peripheral nerve sheath tumors can be de novo sporadic neoplasms or NF1-associated tumors arising through malignant transformation of a (plexiform) neurofibroma.