Diseases of Muscle Flashcards
Duchenne: Onset
childhood (weakness 5-12y)
Duchenne: Inheritance
X linked R
Duchenne: Prognosis
loss of ambulation (move: walk) in teen or early childhood
Duchenne: late in disease symptom
cardiomyopathy
Duchenne: Muscle Biopsy
dystrophic changes, dystrophin staining
Duchenne: Patient Symptoms
young boy usually, walking in the tip of his toes (corta el tendon de aquiles), inability to get up from the floor without help, normal developmental history
Duchenne: Clinical Presentations
Gower’s Sign and calf hypertrophy
Duchenne: CK levels
very high
Are myopathies accompanied by pain?
no
What sensory symptoms do myopathies present?
none
How are myopathies evaluated clinically? What tests?
muscle enzymes (CK), electromyography/nerve conductions, muscle biopsy, genetic testing
What type of molecules cause myopathies?
membrane proteins (such as dystrophin)
What is dystrophin?
muscle membrane structural protein
What mutations are seen in Duchenne? What type of mutations and what gene.
dystrophin, deletions (common) or duplications…non-sense, point mutation… spectrum of disease depending on mutation (unreadable gene or defetive protein)
Duchenne: elevated enzymes
CK, aldolase
Duchenne: treatment
corticosteriods; retard progression
Becker’s: molecular problem
dystrophin present but in reduced amount or defective form
Becker’s vs. Duchenne progression
Beckers is slower
Becker’s vs. Duchenne
Becker’s: cardiac involvment
Gene defects in muscle diseases
deletions, missense, base repeats, point mut, repeat of base seq, mito DNA deletion
Limb Girdle Myopathies: symptom
weakness in proximal muscles
Limb Girdle Myopathies: genetic mutation
wide spectrum of genetic etiologies and patterns of inheritance
Limb Girdle Myopathies: molecular problem
dysfunction of sarcolemal proteins
Limb Girdle Myopathies: genotype
dominant, recessive, X-linked
Limb Girdle Myopathies: age of onset
variable
Limb Girdle Myopathies: CK
elevated
Limb Girdle Myopathies: examples of muscle protein defects
alpha beta gamma sarcoglycan proteins, myofibrillar proteins, caveolins, dysferlin, dystrophin
Myotonic Dystrophy (DM1): genotype
AD, variable penetrance
Myotonic Dystrophy (DM1): chromo mutation
19th Chrm
Myotonic Dystrophy (DM1): genetic mutation
repeats in CTG seq
Myotonic Dystrophy (DM1): onset
earlier
Myotonic Dystrophy (DM1): 2 main clinical presentations
- myotonic dystrophy (98%)
- proximal myotonia, mild or no weakness
Myotonic Dystrophy (DM1): symptoms
cramp-like phenomenon with involuntary persistent muscle contraction (myotonia)
Myotonic Dystrophy (DM1): protein damaged
DMPK (myotonin)
Myotonic Dystrophy (DM1): clinical vignette
39 yr old, elevated CK, no muscle weakness in normal tasks, difficulty with fine motor function, cramping of hands, elongated facies and early cataracts
Myotonic Dystrophy (DM1): EKG
asymptomatic right bundle branch block
Myotonic Dystrophy (DM1): muscles with weakness and atrophy
interossei and abductor pollicis brevis in both hands, wakenes of tibialis anterior limitng foot extension
Myotonic Dystrophy (DM1): classical symptom
handgrip and percussion shows slow release and persisten muscle contraction (myotonia)
Congenital Myopathies: 3 example of diesases
centronuclear (myotubular), nemaline (rod body), central core
Congenital Myopathies: description of umbrella
structural defects of muscle
Congenital Myopathies: symptoms at birth
hypotonia, weak suck reflex, developmental delay
Congenital Myopathies: definite diagnosis
mucsle biopsy or genetic testing
Congenital Myopathies: differential diagnosis
developmental delay due to disorders of nervous system (genetic, metabolic, structural), cerebral palsy, spinal muscular atrophy (infantile), congenital myasthenic syndromes, metabolic muscle conditions
Congenital Myopathies: histology slide characteristic
nucleo de celulas son centrales y no peripherales
Duchenne: histological slide
extensive endomysial fibrosis between fibers, and centrally displaced nuclei, replacement of muscle by fat and CT
Duchenne: atrophied muscles
hombro, pelvico y batata
Diseases that atrophy the hamstring
Duchenne and Beckers
Limb Girdle: body parts with dystrophy
faja pelvica y scapula salida
Congenital Myopathies: pt clinical vignette
bebe, mother uneventful pregnancy, baby observed hypotonic, poor suck and weak limbs, weak cry, good patellar reflexes, normal metabolic and infectious evaluation, normal electroencephalogram and MRI
Congenital Myopathies: CK level
normal
Congenital Myopathies: electromyogram
normal
Congenital Myopathies: nerve conduction studies
normal
Metabolic myopathies: examples of diseases
thyroid myopathy, disordersof glycogen metabolism, lipid metabolism, mito disorders, ion channel disorders (hypo/hyperkalemic paralysis)
Mc Cardle’s Disease: biological dysfunction
myophophorylase deficiency, ineffective glucose metabolism in muscle
Mc Cardle’s Disease: symptoms
cramps, myalgias after exercise
Mc Cardle’s Disease: CK level
elevated
Mc Cardle’s Disease: microbiological effect of disease (what is in excess, what is scarce and when)
lactic acid fails to elevate after exercise, glycogen accumulation in muscle
Mc Cardle’s Disease: enzyme dysfunction name and purpose
myophosphorylase deficiency (muscle isoform of glycogen phosphorylase), glycogen to glucose 1-P`
Mc Cardle’s Disease: histological slide
glycogen accumulation
Carnitine Deficiency: carnitine fxn
transport LCFA across mito membrane
Mc Cardle’s Disease: biological dysfunction
ineffective lipid metabolism in muscle
Mc Cardle’s Disease: what disorder commonly presents this deficiency?
mitochondrial disorders
Mitochondrial Myopathies: inherintance
maternal, non-mendelian
Mitochondrial Myopathies: symptoms
muscle frequently involved, external ophtalmoplegia (paralyisis of extraoccular muscles), systemic involvement
Mitochondrial Myopathies: CK and lactic acid leves
elevated
Mitochondrial Myopathies: clinical presentation in eyes (como se ven)
parpados caidos y los ojos no se mueven
Mitochondrial Myopathies: histologicla slide
fibras desgeneradas y rojizas
Mitochondrial Myopathies: diagnosis
mito genetic testing
Mc Cardles: clinical vignette
19 yr old, severe muscle pain after beginning to workout at they gym, dark urine like coke for several days, muscle cramping after repeated actions (exercise)
Mc Cardles: CK level
supremely elevated
Mc Cardles: muscle strength
normal
Inflammatory myopathies: examples of diseases
dermatomyositis (childhood and adult), polymyositis, inclusion body myositis
Inflammatory myopathies: genetic?
no, acquired
Inclusion body myositis age of onset
50yrs or more
Inflammatory myopathies: etiology
autoimmune related
Inflammatory myopathies: common symptom
inflammation of muscle
Dermatomyositis: CK level
alto
Dermatomyositis: key symptom
rash como psoriasis
Inflammatory myopathies: histological slide
musculo saludable ha sido atacado, H&E: puntitos oscuros infiltrando
Dermatomyositis: clinical symptoms
weakness in proximal more than distal muscles, bulbar 20%, muscle pain, tenderness, discomfort, muscle swelling, arthritis, arthralgias, malaise, contractures in some cases, vasculitis
Dermatomyositis: systemic involvement
cardiac; arrhythmias, muscle…. pulmonary; interstitial ling disease complicates (10-20% of cases)… GI; motility… arthritis, vasculitis
Dermatomyositis: pathophysiology
humoral-mediated microangiopathy
Polymiositis: onset
adult 20 or more yrs
Polymiositis: genetics
more common in females
Polymiositis: symptoms
symmetric proximal weakness, swallowing 1/3rd of patients, muscle tenderness but not as prominent, occasional mild face weakness
Polymiositis: muscle biopsy
muscle fibers: necrosis, variation in fiber size, inflammatory infiltrate, T cell/Macs on non-necrotic muscle cells, perimysial and endomysial infiltrate
weakness in proximal more than distal muscles, bulbar 20%, muscle pain, tenderness, discomfort, muscle swelling, arthritis, arthralgias, malaise, contractures in some cases, vasculitis
Dermatomyositis
young boy usually, walking in the tip of his toes (corta el tendon de aquiles), inability to get up from the floor without help, normal developmental history
Duchenne
39 yr old, elevated CK, no muscle weakness in normal tasks, difficulty with fine motor function, cramping of hands, elongated facies and early cataracts
Myotonic Dystrophy
19 yr old, severe muscle pain after beginning to workout at they gym, dark urine like coke for several days, muscle cramping after repeated actions (exercise)
Mc Cardles
bebe, mother uneventful pregnancy, baby observed hypotonic, poor suck and weak limbs, weak cry, good patellar reflexes, normal metabolic and infectious evaluation, normal electroencephalogram and MRI
Congenital Myopathies
Parents bring a 6-year-old boy to the pediatrician
concerned about frequent walking in the tip of his toes and more recently inability to get up from the floor without help. The boy refuses to climb stairs asking to be carried up by the parents. Developmental history is completely normal with normal motor milestones attained before the present symptoms appeared. On examination, the child has a Gower’s sign and calf hypertrophy is observed. There are mild contractures of the Achilles’ tendon. The pediatrician refers the patient to a pediatric neurologist and obtains a Creatine Kinase (CK) level. The pediatrician receives a call from the local laboratory when the result of this test reveals a CK level of 18,950 IU (normal up to 350).
Duchenne
A 39-year-old woman is referred to a
neurologist when her primary physician found
a Creatine Kinase of 1,200 IU (normal up to
250IU) on a routine laboratory evaluation.
Upon questioning the patient denies weakness
in talks as getting up from chairs, climbing
stairs or drying her hair with a blower. She
however has observed difficulty buttoning her
garments and writing in the computer. She also
describes frequent “cramping” of the hands.
On examination, mild weakness and atrophy of
the interossei and the Abductor Pollicis Brevis
is identified in both hands. She also has
weakness of the Tibialis Anterior limiting her
foot extension. Handgrip and percussion
shows slow release and persistent muscle
contraction. She has elongated facies and early
cataracts. An EKG obtained by her primary
physician showed an asymptomatic Right
bundle branch block.
Myotonic Dystrophy
A 56 year-old woman previously in good health
began six months ago with muscle aches,
slowness climbing upstairs, difficulty keeping
her arms up hanging clothes and in the last
week became unable to rise from the toilet
requiring the help of her sister. She has also
observed a rash in her chest and knuckles and
was told this might be psoriasis by a friend.
She had an initial evaluation by a local
physician who suspected she might be
developing “fibromyalgia” reason for which the
doctor referred her to a neurologist and a
rheumatologist. On her initial visit with the
neurologist she was brought in a wheelchair
since she could only take steps. Her laboratory
studies showed the following results: CK 8,406
(normal up to 250), ANA 1:320 (antinuclear
antibody), sedimentation rate 66.
Dermatomyositis
A baby girl is born form a healthy 26-year-old
mother with an uneventful pregnancy. The
baby is observed to be hypotonic (“floppy”)
with poor suck and weak limbs. Cry is also
weak. Patellar reflexes are present. A
metabolic and infectious evaluation is normal.
Electroencephalogram and MRI of the brain
are also normal. CK is 500 (normal up to 500
IU). Cell count and Chemistries are also
normal. An electromyogram and nerve
conduction studies do not reveal any definite
abnormalities. The neurology service is
consulted for further evaluation.
Congenital Myopathies
A 19 year-old man in good health is referred to his
physician after he developed severe muscle pain after
beginning to workout in the gym. He gives history of
passing dark urine like “Coca-cola” for several days.
Routine laboratory tests showed a CK of 19,506.
Several weeks later CK had returned to almost normal
levels (500 IU). Examination was normal including
muscle strength. The patient gave history of muscle
cramping after repeated actions such as biceps curls
or using a wrench. He described that after few
minutes of such actions he develops cramps in the
muscles used.
Mc Cardles
What procedures are useful when evaluating a patients with muscle diseases?
clinical history, examination of muscle strength and fxn, examination of family members, genetic tests, nerve conduction and electromyography, CK levels, and muscle biopsy
Important clnical tests to diagnose muscle diseases:
CK levels, electromyography and nerve conductions, muscle biopsy, and genetic tests
Herediatry Muscle Disorders:
duchennes, myotonic dystrophy, and limb girdle muscular dystrophy
