Diseases of Muscle Flashcards
T/F
Eye muscles do not contain dystrophin.
True
Normal muscle is endowed with a population of embryonic muscle precursor cells known as _______ cells and as a result, it possesses a remarkable capacity to regenerate.
satellite cells
Muscle connective tissue derives from the
somatopleural mesoderm
At all ages, disuse of muscle decreases fiber size by a smuch as ____ percent and overuse increases the size by about the same amount.
30%
6 Grades of Muscle strength by the Medical Research Council of GB
0 complete paralysis
1 minimal contraction
2 active movement only with gravity eliminated
3 full movement against gravity but cannot offer resistance to manual muscle opposition
4 active movement against gravity and resistance but can be overcome by manual muscle opposition
5 normal strength
stiffness and slowness of contraction in a muscle such as the quadriceps may be seen on change in postures
contraction myoedema
prolonged failure of relaxation, following contraction of a muscle is characteristic of
myotonia
T/F
Pain tends to be prominent in polymyositis and dermatomyositis.
False
pain tends NOT to be prominent but there are exceptions
p1411
T/F
As a general rule, muscle diseases are identified by a predominantly proximal weakness that is symmetric.
true
T/F
When weakness of the orbicularis oculi (muscles of eye closure) is added to weakness of eye opening (levator palpebrae; ptosis), it nearly always signifies myasthenia gravis and occasionally, a rare primary disease of muscle (progressive external ophthalmoplegia [PEO]).
true
T/F
Paradoxical inward movement of the abdomen with inspiration is another sign of diaphragm weakness.
True
p1414
Most common pattern of a number of myopathies.
most often, polymyositis, IBM, dermatomyositis, and the muscular dystrophies present in this fashion
Proximal Limb-Girdle palsies presenting as inability to raise arms or to arise from a squatting, kneeling or sitting position
weakness of IBM has a preference for certain sites
quadriceps or of the forearm muscles particularly the long finger flexors
flexor digitorum profundus
parasitic disease
ocular muscle weakness, causes strabismus and diplopia
tongue weakness -> dysarthria
weakness of masseter and pharyngeal muscles - diff chewing and swallowing
weakness of limb muscles proxima>distal
conjunctival, orbital, facial edema
subconjunctival, subungual splinter hemorrhages
dx: puffy face with tender muscles
eosinophilia >700
ELISA is accurate but positive only after 2 weeks of illness
biopsy is the most reliable confirmatory test
biopsy: segmental necrosis, interstitial inflammatory infiltrates, eosinophils
Trichinosis
caused by nematode Trichinella spiralis
treatment for Trichinosis
no treatment in most cases
severe weakness and pain: thiabendazole 25-50mg/kg daily in divided doses for 5-10 days
prednisone 40-60mg/kg per day
albendazo,e 400mg OD
recovery is complete
except in pts with infarcts
In the AIDS population, myositis from toxoplasma is more common than brain infestation
False
p1416
brain infestation more common
treatment for toxoplasmosis myositis
sulfadiazine in combi with pyrimethamine or trisulfapyrimidine
folic acid is given in addition
an antiretroviral drug used to treat HIV, may induce a myopathy with myalgia and weakness that is indistinguishable from HIV myopathy
zidovudine
T/F
The clinical features of putative ZVD-induced myopathy are much the same as those of HIV myopathy except that moderate pain is said to be characteristic of the druginduced variety
True
T/F
The myopathologic changes in AIDS are also like those of idiopathic polymyositis.
true
idiopathic subacute or chronic symmetrical weakness of proximal limb and trunk muscles without dermatitis
Polymyositis
insidious, course progressive several weeks to months
febrile illness or benign infection may precede the weakness
painless weakness
T/F
Ocular muscles are not affected in PM.
True
but there are rare instances of combined PM and MG
denominative feature is rash
most often, the skin changes precede the muscle syndrome
localized or diffuse erythema, maculopapular eruption, scaling eczematoid dermatitis, exfoliative dermatitis
prominent in childhood DM: Gottron papules
heliotrope
V sign and shawl sign
Dermatomyositis
T/F
Serum CK levels tend to be higher in PM than in DM.
true
because of the widespread single-fiber necrosis in the former. however in DM if there are infarcts in muscle, CK levels will be moderately elevated as well
ESR is normal or mildly elevated
T/F
Absent or low titer ANA and normal ESR do not exclude the diagnosis of PM.
true
T/F
When performing EMG and biopsy, perform the needle examination and biopsy on the same side and site.
False
p1421
EMG on one side and biopsy on the other side
pathologic changes in idiopathic PM
widespread destruction of segments of muscle fibers with an inflammatory reaction - phagocytosis of muscle fibers by mononuclear cells and infiltration with a varying number of lymphocytes and lesser number of other mononuclear or plasma cells
characteristic pathologic changes in Dermatomyositis
perifascicular muscle fiber atrophy
others: inflammatory infiltrates in DM predominate in perimysial connective tissue, in PM: most prominent in relation to the muscle fiber membrane and endomysium
distinctive microvascular changes in muscle in dermatomyositis
endothelial alterations (tubular aggregates in the endothelial cytoplasm) occlusion of vessels by fibrin thrombi
in Dermatomyositis, what are deposited in the walls of venules and arterioles indicating that immune response is directed primarily against intramuscular blood vessels
immune complexes, IgG, IgM, C3 and membrane attack complexes
In Polymyositis, there are a large number of _____ cells. In Dermatomyositis, there are a larger number of _____ cells.
PM - activated T cells - cytotoxic
DM - B cells - humoral
treatment for PM and DM
corticosteroids
prednisone 1mg/kg as a single daily dose orally or IV
acute and severe case, high dose methylprednisolone
1g infused over 2 hours each day for 3-5 days
monitoring parameters in DM and PM treatment
muscle strength and serum CK measurement
T/F
DM and PM treatment.
In patients who respond, the serum CK decreased before the weakness subsides and with relapse, the serum CK rises before weakness returns.
True
when to give IVIg in DM
when patients responds poorly to steroids and other immunosuppressants or are severely affected early on,
several courses of treatment at monthly intervals may be required to achieve sustained improvement
Other immunosuppresants for PM and DM
azathioprine methotrexate cyclophosphamide rituximab cyclosporine mycophenolate mofetil
Prognosis in PM and DM
generally favorable except for patients with malignancy
most common inflammatory myopathy in patients older than 50 years
inclusion body myositis
Defining features of IBM
intracytoplasmi and intranuclear inclusion
T/F
in IBM.
Associations with malignancy or systemic autoimmune disease have been established.
False
Have NOT been established
weakness presentation in IBM
more focal than PM and DM
steadily progressive painless muscular weakness and modest atrophy
weakness: distal in arms and both proximal and distal in legs
focal weakness of quadriceps, finger or wrist flexors, or lower leg muscles on one or both sides
selective weakness of flexor pollicis longus is a particularly characteristic pattern of involvement
Lab/diagostic features in IBM
serum CK
EMG
biopsy
serum CK is normal or slightly elevated - generally loer levels than in PM
EMG - same i PM, myopathic pattern but in a proportion may show neuropathic pattern
biopsy - intracytoplasmic, subsarcolemmal
vacuoles and eosinophilic inclusions in both the
cytoplasm and nuclei of degenerating muscle fibers (Gomori trichome in frozen sections)
rimmed vacuoles
Treatment for IBM
IBM has not responded in any consistent fashion to treatment with corticosteroids or other immunosuppressive drugs
greatly thickened fascia, extending from the subcutaneous tissue to the muscle and infiltrated
with plasma cells, lymphocytes, and many eosinophils
ages of 30 and 60 years and are often precipitated
by heavy exercise
low grade fever and myalgia followed by the subacute development of diffuse cutaneous thickening and limitation of movement of small and large joints
proximal muscle weakness and eosinophilic infiltration of
muscle can be demonstrated
Eosinophilic Fasciitis
T/F
Eosinophilic Fasciitis
Repeated examinations of the blood disclose an eosinophilia in most but not all patients.
True
Treatment for Eosinophilic Fasciitis
Steroids
Painful swelling of a calf muscle or, less frequently, some other muscle has been the chief characteristic of this disorder.
Biopsy discloses inflammatory necrosis and edema of the interstitial tissues; the infiltrates contain large but variable
numbers of eosinophils
The response to prednisone was dramatic;
the swelling and pain subsided in 2 to 3 weeks and her
power of contraction was then normal
Eosinophilic monomyositis
The features of the muscle disorder were
typical of PM except that the inflammatory infiltration was
predominantly eosinophilic and the muscles were swollen
and painful.
systemic manifestations include: eosinophilia, cardiac involvement, vascular disorder (Raynaud, subungual hemorrhages) pulmonary infiltrates, strokes, anemia, neuropathy, hypergammaglobulinemia.
Eosinophilic Polymyositis
A proportion of patients with Eosinophilic Polymyositis are attributable to mutations in
CAPN3
gene for calpain-3
severe generalized myalgia and eosinophilia
of the peripheral blood following the ingestion of
contaminated L-tryptophan,
onset of the muscular illness was relatively
acute, with fatigue, low-grade fever, and eosinophilia
(>1,000 cells /mm3)
Muscle pain and tenderness, cramps, weakness, paresthesias of the extremities, and induration
of the skin were the main clinical features.
A severe axonal neuropathy with slow and incomplete recovery was associated in some cases
Eosinophilia-Myalgia Syndrome
most frequent and best known of the early-onset muscular dystrophies
Duchenne Muscular Dystrophy
X-linked recessive, dystrophin gene
begins in early childhood and runs a relatively rapid, progressive course
X-linked recessive trait
rarely, a severe proximal Duchenne-type muscular
dystrophy occurs in young girls- female may have only 1 X chromosome, as occurs in the Turner or or the Lyon
principle may be operative; that is, there is inactivation of
the unaffected paternal X chromosome allowing expression of the mutated Duchenne protein from the maternal chromosome in a large proportion of embryonic cells (mosaicism)
usually recognized by the third year of life and almost always before the sixth year
greatly elevated CK
Increasing difficulty in walking, running, and climbing stairs, excessive lumbar lordosis, and waddling gait
there may be pseudohypertrophy
Gower sign
The tendon reflexes are diminished and then lost as
muscle fibers disappear
Duchenne Muscular Dystrophy
In duchenne MD, which muscles are affected that account for a lordotic posture and protuberant abdomen when standing and the rounded back when sitting
weakness of abdominal and paravertebral muscles
describe habitual posture of patient with DMD
lumbar lordosis, hip flexion and abduction, knee flexion, and plantar flexion
serum CK values in DMD
25 to 200 times normal
age of onset: mean 12yrs, range 5-45yrs
X-linked
not uncommon to walk well in adult life
causes weakness and hypertrophy in muscles affected by a more severe X-linked recessive dystrophy
Becker Muscular Dystrophy
Pathology of Duchenne and Becker Dystrophies
early stages of Duchenne dystrophy: the most distinctive
features are prominent segmental degeneration
and phagocytosis of single muscle fibers or groups of
fibers and evidence of regenerative activity
the protein dystrophin is express in what parts of the body
skeletal, cardiac, smooth muscles
brain
T/F
Whereas dystrophin is absent in patients with the
Becker phenotype, it is present but structurally abnormal
in the Duchenne type.
False
absent in Duchenne
T/F
The dystrophin-glycoprotein complex functions in this scheme as a transsarcolemmal structural link between the subsarcolemmal cytoskeleton and the extracellular matrix.
True
X-linked muscular dystrophy
deficiency in the protein emerin, a constituent of nuclear membrane
Weakness affects first the upper arm and pectoral girdle musculature and later the pelvic girdle and the distal muscles in the lower extremities
distinguishing feature of the disease is the early
appearance of contractures in the flexors of the elbow,
extensors of the neck, and posterior calf muscles.
no hypertophy or pseudohypertrophy
severe cardiomyopathy with variable sinoatrial
and atrioventricular conduction defects is a common
accompaniment
Emery-Dreifuss Muscular Dystrophy
slowly progressive dystrophy involving primarily
the musculature of the face and shoulders, often
with long periods of nearly complete arrest
autosomal dominant
age of onset 6-20 yrs
first manifestations are difficulty in raising
the arms above the head and winging of the scapulae,
although bifacial weakness may have initially attracted
attention, even in early childhood
There is an inability to close the eyes
firmly, to purse the lips, and to whistle; the lips have a
peculiar looseness and tendency to protrude. The lower
parts of the trapezius muscles and the sternal parts of the
pectorals are almost invariably affected
Usually the biceps waste less than
the triceps, and the brachioradialis muscles even less,
so that the upper arm may be thinner than the forearm
(“Popeye” effect)
An interesting feature of this group of diseases is the
occasional congenital absence of a muscle (amyoplasia
of one pectoral, brachioradialis, or biceps femoris) or
part of a muscle in patients who later develop the typical
features of the disease
Fascioscapulohumeral Muscular Dystrophy
(Landouzy-Dejerine Muscular Dystropy)
deletions in a repeated segment
allow the expression of normally inactive
genes such as DUX4.
slowly progressive myopathy primarily
involving and often limited to the extraocular muscles.
the levators of the eyelids are the first to be
affected, causing ptosis, followed by progressive balanced ophthalmoparesis
The eyelids are abnormally thin due to atrophy of the levator muscles. The orbicularis oculi muscles are frequently involved in addition to the
extraocular muscles.
The characteristic feature is that ptosis and ocular paralysis precede involvement of other muscles by many years.
Progressive External Ophthalmoplegia
T/F
The pupillary responses and accommodation
are normal in PEO.
True
Mutations in three nuclear genes in PEO have been implicated
twinkle, a mitochondrial DNA binding protein;
ANT1 , an adenine nucleotide transporter in the intermembrane space in the mitochondrion;
and POLG, a subunit of the mitochondrial
DNA polymerase
