Muscle Diseases

Muscle Diseases

Clinical patterns of muscle disease

Weakness: Proximal; Symmetric;
Persistent
Weakness > Wasting
Sensory: Normal
Tendon reflexes: Decreased only in
areas of prominent weakness
Other features in some myopathies
Myotonia
Rhabdomyolysis
Cardiomyopathy

Laboratory Tests

Muscle enzymes
EMG
Muscle Pathology
Muscle Imaging
Genetic Evaluation

MUP - MOTOR UNIT

POTENTIAL

Recruitment and Interference

Pattern

EMG - NEUROGENIC
PATTERN
Positive Sharp Waves

Fasciculations

Fibrillation

Complex Repetitive Discharge

EMG MYOPATHIC PATTERN

Short, Thin and Polyphasic

Early Recruitment

Early Interference

Muscle Pathology - Normal

Muscle

Muscle Pathology
Fiber Size

H&E stain Small Fibers

ATPase pH 9.4 stain - Large fibers

Muscle Pathology
Necrotic Fibers

H&E

Muscle Pathology
Ragged red muscle fiber

Gomori trichrome stain

Muscle Pathology Histochemistry

Fiber Type

Muscle Pathology Inflammation

Congo red stain

Esterase stain

CD68 stain

Muscle Pathology ImmunoHistrochemistry

Muscle Pathology Electron

microscopy

559781160004923

Muscle Imaging

The Muscular Dystrophies

progressive hereditary degenerative
diseases of skeletal muscles.

Duchenne muscular dystrophy

Guillaume-Benjamin
Duchenne de Boulogne

DMD Clinical Features

Onset 3 to 5 yrs
Weakness: Proximal > Distal; Symmetric;
Legs & Arms
Steady decline in strength: After 6 to 11
years
Waddling gait
Failure to walk: 9 - 13 years; Later with
steroid treatment

DMD Clinical Features

Gowers sign:
Standing up with
the aid of hands
pushing on knees

DMD Clinical Features

Muscle hypertrophy

Especially calf
May be generalized
Increases With age
Due to muscle fibrosis,
not enlarged muscle
fibers

DMD Clinical Features

Contractures
Scoliosis after loss of ambulation
Cardiomyopathy: Dilated; Especially > 15
years
Mental retardation: Mean IQ ~ 88
Night blindness
Progression: Death 15 - 25 years due to
respiratory or cardiac failure

DMD - Dystrophin gene

Chromosome Xp
79 Exons
Exons are only 0.6% of gene

Dystrophin mRNA
Size: 14kb
Encodes 3685 amino acid 427kDa protein

7 different dystrophin transcripts with

Muscle, Cortical, Purkinje Cell, Retinal, Schwann Cells
Genotype: Dystrophin
96% with frameshift mutation
30% with new mutation

DMD - Dystrophin
Dystrophin Localization: Subsarcolemmal
region in skeletal and cardiac muscle
Dystrophin functions
Stabilizaton of membrane during contraction
& relaxation
Part of link between intracellular cytoskeleton
& extracellular matrix

DMD - Laboratory features

Serum
CK: Very high
Troponin I: Elevated above normal but not to
levels in cardiac ischemia
Liver enzymes: High AST & ALT

EMG
Myopathic pattern

DMD Muscle Pathology

Biopsy from 5 yr old
boy

Biopsy from 10 yr old

boy

Endomysial connective tissue.

Variable fiber size.
Small fibers are rounded.

Markedly connective tissue.

Many hypercontracted muscle
fibers

DMD Muscle Pathology

Dystrophin staining

Normal dystrophin
staining
around the rim of muscle
. fibers

Absent dystrophin: Duchenne muscular

dystrophy
Left: No staining around the rim of muscle
fibers.
Right: No staining of most muscle fibers.
One "revertant" fiber with dystrophin
staining.

DMD: Therapy
Drug treatment: Prolongs ability to walk by 2 to 3
years
Prednisone

Prolongs walking by 2 to 3 years

Increased Strength
Falling reduced
Most beneficial while patient still ambulatory

Myoblast therapy
Gene therapy
Carrier Evaluation
Perinatal Consultation

Myotonia: General features

Clinical: Delayed relaxation of skeletal
muscle following voluntary contraction
Present with initial activity
Usually abates after repeated muscle
activity
Classification by ion channel disorder
EMG: Myotonia

Myotonic Dystrophy: Clinical

features
General
Marked variation in severity within families
Anticipation
Strong relationship of clinical syndromes to
age of patient and age of onset

Onset: Neonatal to late adulthood

Myotonic Dystrophy: Clinical

features
Weakness
Cranial
Face: Superficial muscles; Temporalis
Ptosis (Symmetric; Partial): Levator palpebrae
superioris;
Masseter
Palate Tongue: Indistinct speech

Neck: Flexors & Sternomastoids

Myotonic Dystrophy: Clinical

features
Myotonia
Evoked by percussion or muscle contraction
Onset: 5 to 25 years; Not congenital
Rarely causes disability
Treatment: Little functional benefit

Myotonic Dystrophy: Clinical

features
CNS
Personality: Avoidant; Apathy
Hypersomnia
Excessive daytime sleepiness

Mental retardation (10% to 24%): Congenital;

Non-progressive

PNS
Mild sensory neuropathy (Rarely functionally
significant(

Myotonic Dystrophy: Clinical

features
Face

Frontal balding
Temporal wasting
Ptosis
Hatchet face

Eyes

Cataracts
Ptosis
Retinal degeneration
Ciliary body weakness (Low intraocular tension(

Myotonic Dystrophy: Clinical

features
Cardiac:
Conduction defects: Ectopic beats; Sudden death
Tachyarrhythmias
Cardiomyopathy

Gastrointestinal: Dysphagia (Pharyngeal or

Esophageal); Megacolon; Cholelithiasis;
Constipation
Skeletal
Small sella turcica
Frontal bossing

Myotonic Dystrophy: Laboratory

features
CK: Normal to 3x
EMG
Myotonia
After 1st decade
Not present early in congenital MyD

Myopathic potentials: Distal > Proximal

Genetic testing
Muscle biopsy
Myopathic changes

Myotonia treatment

Quinine
Mexiletine
Dilantin
Procainamide
Carbamazepine
Acetazolamide

Dermatomyositis: Clinical
features
Frequency: > 90% of
inflammatory
myopathies in
children
Skin - Erythematous
rash: Heliotrope

Dermatomyositis: Clinical
features

Gottron's papules
Erythema

Dermatomyositis: Clinical
features
Muscle weakness: Proximal; Dysphagia
Joint contractures
Other occasional systemic features
Ocular: Retinopathy; Conjunctivitis; Iritis;
Uveitis
Cardiac

Dermatomyositis:
Malignancy associated
Females; Age related
Neoplasms
Ovarian advanced stage
Small cell carcinoma, lung

Dermatomyositis: Laboratory
features
Serum CK: Normal or High (up to 30 times
normal)
Antibodies: Mi-2 & Jo-1
Myoglobinuria (sustained): May be presenting
feature
EMG: Irritative myopathy
Motor units: Small amplitude; Brief; Polyphasic
Spontaneous activity: Fibrillations; Positive sharp
waves

Dermatomyositis: Laboratory
features
DM: Pathology
Muscle fibers: Perifascicular pathology
Myopathic changes: Necrosis + phagocytosis;
Regeneration
Muscle fiber atrophy

Vessels
Microvascular deposits

Inflammation - Usually perivascular

Dermatomyositis: Muscle
Pathology

Dermatomyositis: Treatment
options
Prednisone
Oral 100 mg q.d.; then taper
Latency before benefit: 1 to 6 months

Solumedrol (i.v.): Fewer side effects than oral

prednisone
Azathioprine
2.5 - 3mg/kg/day
Used to reduce Prednisone dose
Latency before benefit: 6 to 12 months

Methotrexate
Cyclosporine
IVIg

Dermatomyositis: Prognosis worse

Cardiac involvenment
Acute onset
Fever
Arthritis
Hypergammaglobulinemia
Lung fibrosis

IBM: Clinical features

Muscles commonly spared
Deltoid
Pectoralis
Interossei (Hands)
Face

Progression
Slow over 5 to 20 years
More rapid progression to disability with onset
after 60 years

IBM: Clinical features

Dysphagia (30%): Upper 1/3 of
esophagus; Especially females
Polyneuropathy
Usually subclinical
Sensory > Motor
Loss of myelinated axons in sural nerve

IBM: Laboratory
Serum CK: Mildly elevated 2 to 5 fold; May be
normal
EMG: Irritable myopathy; Long duration
potentials may occur
Barium swallow: Cricopharyngeus dysfunction
Nerve conduction studies: Absent sural
potentials in some patients > 60 years
Muscle MRI: Fatty infiltration of medial head of
gastrocnemius

IBM: Muscle Pathology

Mitochondrial disorder: COX- muscle fibers &
multiple mDNA deletions in 50% of IBM
Muscle fiber hypertrophy: More common than
in polymyositis

IBM: Muscle Pathology

Rimmed vacuoles with granular material & filaments
Histochemistry: Best visualized with Congo Red stain
Contain
Filaments: 15 to 18 nm
Several proteins b-Amyloid, Desmin; Ubiquitin;
Transglutaminases 1 & 2

IBM: Electron Microscopy

IBM: Treatment
None
Few reports of response to IV Ig or
immunoabsorption

Hereditary IBM: Clinical

Features

Onset: 2nd or 3rd decade

Early: Peroneals
Distal & Proximal
Lower extremity
Onset: Peroneal weakness (Anterior distal legs)
Then: Hips & Hamstring

Upper extremity: Shoulder girdle; Wrist

extension; Hands
Sparing: Quadriceps; Deltoids
Weak in some patients: Disease progression

Hereditary IBM: Clinical

Features
Neck flexors may be weak
Cranial nerves: Spared
Rare ptosis
No facial weakness

Progression: slow
Disability within 10 to 20 years of onset
Often become wheel chair dependent
Weakness may remain distal or involve
proximal muscles of arms legs or neck