All types have been covered with enough details

1. Myopathies
Presented by,
Dr. Chandan N
Intern, Department of Medicine,
MIMS, Mandya

2. Definition
• Myopathies are disorders with structural
changes or functional impairment of muscle.
• It does not include upper motor neuron
lesions, lower motor neuron lesions,
myasthenia gravis which also causes muscle
weakness.

3. Muscle anatomy and microscopy

4. UMN and LMN lesions

5. Myasthenia gravis

6. Types of myopathies
Inflammatory Myopathies
 Polymyositis
 Dermatomyositis
 Inclusion body myositis
Muscular dystrophies
 X-linked
 Limb-girdle(ar/d)
 Congenital
 Fasioscapulohumeral (ad)
 Oculopharyngeal
Myotonic Syndromes
 Myotonic dystrophy (ad)
 Inherited
 Schwarz-Jampel
 Drug-induced
Congenital myopathies
 Central core disease
 Nemaline myopathy
 Myotubular
Metabolic myopathies
 Glycogen storage disorders
 Mitochondrial
 Periodic paralysis
Endocrine myopathies
 Thyroid
 Parathyroid
 Adrenal/steroid
 Pituitary
Drug-induced/toxic

7. Inflammatory myopathies

8. Characteristic Polymyosit
is
Dermatomyositis Inclusion Body Myositis
Age at onset >18 yr Adulthood and childhood >50 yr
Familial association No No Yes, in some cases
Extramuscular
manifestations
Yes Yes Yes
Associated conditions
Connective tissue
diseases
Yes Scleroderma and mixed
connective tissue disease
(overlap syndromes)
Yes, in up to 20% of casesa
Systemic autoimmune
diseases
Frequent Infrequent Infrequent
Malignancy No Yes, in up to 15% of cases No
Viruses Yes Unproven Yesc
Drugs Yes Yes, rarely No
Parasites and bacteria Yes No No

9. Pathogenesis
• An autoimmune etiology of the inflammatory
myopathies is indirectly supported by an
association with other autoimmune or connective
tissue diseases; the presence of various
autoantibodies(anti-Jo-1 antibodies ); an
association with specific major histocompatibility
complex (MHC) genes; demonstration of T cell–
mediated myocytotoxicity or complement-
mediated microangiopathy; and a response to
immunotherapy.

10. Clinical features
 Prevalence is around 1 in 1,00,000.
 Progressive and symmetrical muscle
weakness.
 Proximal muscle weakness occurs first, later
distal muscle weakness, fine movements still
later.
 Ocular muscles are spared even in advanced
and untreated cases.

11. • Facial muscles are unaffected in polymyositis
and dermatomyositis, but mild facial
weakness is common in inclusion body
myositis.
• Pharyngeal muscles and neck muscles are
involved in all forms causing dysphagia and
difficulty in holding head.
• In advanced and rarely acute cases
respiratory muscles are involved.
• Sensations remains intact.
• Tendon reflexes are usually preserved.

12. • Dermatomyositis is identified by its
characterisitic rash often preceding weakness.
-Blue-purple discoloration on the upper eyelids
with edema (heliotrope rash; see Fig. 55-3), a
flat red rash on the face and upper trunk, and
erythema of the knuckles with a raised
violaceous scaly eruption (Gottron's sign)
- Rash may worsen after sun exposure.

13. Diagnosis
Polymyositis
Criterion Definite Probable Dermatomyositis Inclusion Body
Myositis
Myopathic muscle
weaknessa
Yes Yes Yesb Yes; slow onset, early
involvement of distal
muscles, frequent
falls
Electromyographic
findings
Myopathic Myopathic Myopathic Myopathic with
mixed potentials
Muscle enzymes Elevated (up to 50-
fold)
Elevated (up to 50-
fold)
Elevated (up to 50-
fold) or normal
Elevated (up to 10-
fold) or normal
Muscle biopsy
findingsc
"Primary"
inflammation with
the CD8/MHC-I
complex and no
vacuoles
Ubiquitous MCH-I
expression but
minimal
inflammation and no
vacuolesd
Perifascicular,
perimysial, or
perivascular
infiltrates,
perifascicular atrophy
Primary inflammation
with CD8/MHC-I
complex; vacuolated
fibers with -amyloid
deposits; cytochrome
oxygenase–negative
fibers; signs of
chronic myopathye
Rash or calcinosis Absent Absent Presentf Absent

14. Treatment
• Glucocorticoids: Prednisolone 1mg/kg/day for 3-
4 weeks then tapered.
• Immunosuppressive agents: Azathoiprine,
methotrexate, mycophenolate, cyclosporine,
tacrolimus, cyclophosphamide.
• IVIg.
• IBM is resistant to treatment. The combination of
above may be tried. Or low dose prednisolone on
alternate days can be tried.

15. Muscular Dystrophies
• Muscular dystrophy refers to a group of
hereditary progressive diseases each with
unique phenotypic and genetic features

16. Duchenne’s muscular dystrophy
• Also called pseudo hypertrophic muscular
dystrophy.
• It is an X linked recessive disorder.
• Dystrophin is deficient.
Clinical features:
• It is present at birth but becomes evident at 3-
5 years.
• Gower’s maneuver
• Joint contractures, scoliosis, decreased
pulmonary functions.

17. Gower’s maneuver

18. • By 16 to 18 years patients die of severe
pulmonary infections or aspiration
pneumonia.
• Respitatory failure in 2nd or 3rd decade.
• IQ <~1 SD of the mean.
Laboratory findings
• Serum CK levels are raised 20 to 100 times
• EMG shows reduced amplitude.
• Muscle biopsy: small group of necrotic and
regenerating muscle fibres. Connective tissue
and fat replace muscle fibres.

19. • Definitive diagnosis is by demonstrating
dystrophin deficiency and mutation of gene
coding for dystrophin.
Treatment
• Prednisolone – 0.75mg/kg/day significantly
slows down the progression of disease.

20. Becker’s muscular dystrophy
• X linked recessive inheritance.
• Less severe form.
• Dystrophin muscle protein is deficient.
Clinical features:
• Muscle wasting resembles Duchenne’s.
• Proximal muscle weakness of lower extremities
occur first.
• Onset 5-15 years or even 3rd to 4th decade.
• Patients may survive till 4th or 5th decade.

21. • Laboratory findings are similar to that of
Duchenne’s muscular dystrophy.
• No satisfactory treatment yet available.

22. Limb girdle muscular dystrophies(Autosomal Dominant)
Disease Clinical Features Laboratory Features Locus or Gene
LGMD1A Onset 3d to 4th decade
Muscle weakness affects distal limb muscles, vocal cords, and pharyngeal
muscles
Serum CK 2 x normal
EMG mixed
myopathy/neuropathy
NCS normal
Myotilin
LGMD1B Onset 1st or 2d decade
Proximal lower limb weakness and cardiomyopathy with conduction defects
Some cases indistinguishable from Emery-Dreifuss muscular dystrophy with
joint contractures
Serum CK 3–5 x
normal
NCS normal
EMG myopathic
Lamin A/C
LGMD1C Onset in early childhood
Proximal weakness
Gowers' sign, calf hypertrophy
Exercise-related muscle cramps
Serum CK 4–25 x
normal
NCS normal
EMG myopathic
Caveolin-3
LGMD1D Onset 3d to 5th decade
Proximal muscle weakness
Cardiomyopathy and arrhythmias
Serum CK 2–4 x
normal
NCS normal
EMG myopathic
Linked to
chromosome 7q
Gene unidentified
LGMD1E Childhood onset
Proximal muscle weakness
Serum CK usually
normal
NCS normal
EMG myopathic
Linked to
chromosome 6q23
Gene unidentified

23. Limb girdle muscular dystrophies(Autosomal Recessive)
Disease Clinical Features Laboratory Features Locus or Gene
LGMD2A Onset 1st or 2d decade
Tight heel cords
Contractures at elbows, wrists, and fingers; rigid spine in some
Proximal and distal weakness
Serum CK 3–15 x normal
NCS normal
EMG myopathic
Calpain-3
LGMD2B Onset 2d or 3d decade
Proximal muscle weakness at onset, later distal (calf) muscles affected
Miyoshi myopathy is variant of LGMD2B with calf muscles affected at onset
Serum CK 3–100 x normal
NCS normal
EMG myopathic
Inflammation on muscle biopsy may
simulate polymyositis
Dysferlin
LGMD2C–F Onset in childhood to teenage yrs
Clinical condition similar to Duchenne and Becker muscular dystrophies
Cardiomyopathy uncommon
Cognitive function normal
Serum CK 5–100 x normal
NCS normal
EMG myopathic
, , , sarcoglycans
LGMD2G Onset age 10 to 15
Proximal and distal muscle weakness
Serum CK 3–17 x normal
NCS normal
EMG myopathic
Telethonin
LGMD2H Onset 1st to 3d decade
Proximal muscle weakness
Serum CK 2–25 x normal
NCS normal
EMG myopathic
TRIM32 gene
LGMD2I Onset 1st to 3d decade
Clinical condition similar to Duchenne or Becker dystrophies
Cardiomyopathy (some not all)
Cognitive function normal
Serum CK 10–30 x normal
NCS normal
EMG myopathic
Fukutin-related protein
LGMD2Ja Onset 1st to 3d decade
Proximal lower limb weakness
Mild distal weakness
Progressive weakness causes loss of ambulation
Serum CK 1.5–2 x normal
NCS normal
EMG myopathic
Titin

24. Type Inheritan
ce
Defective
Gene/Protein
Onset Age Clinical
Features
Other Organ
Systems
Involved
Facioscapulohum
eral
AD Deletion,
distal 4q
Before age 20 Slowly
progressive
weakness of
face, shoulder
girdle, and
foot
dorsiflexion
Deafness
Coats' (eye)
disease
Oculopharyngeal AD Expansion,
poly-A RNA
binding
protein
5th to 6th
decade
Slowly
progressive
weakness of
extraocular,
pharyngeal,
and limb
muscles
—

25. Facioscapulohumeral dystrophy

26. • Treatment of Facioscapulohumeral (FSH)
Muscular Dystrophy : No specific treatment.
• Treatment of oculopharyngeal dystrophy:
Cricopharyngeal myotomy may improve
swallowing.
• Eyelid crutches may be used in ptosis to
improve vision.
• Except in severe facial weakness ptosis
surgeries can be tried.

27. Congenital muscular dystrophies
Disease Clinical Features Laboratory Features Locus or Gene
Merosin deficiency Onset at birth with hypotonia, joint contractures, delayed milestones, generalized
muscle weakness
Cerebral hypomyelination, less often cortical dysplasia
Normal intelligence usually, some with MR (~6%) and seizures (~8%)
Partial deficiency leads to milder phenotype (LGMD picture)
Serum CK 5–35 x normal
EMG myopathic
NCS abnormal in some cases
Laminin 2 chain
Fukitin-related protein
deficiencyb
Onset at birth or shortly after
Hypotonia and feeding problems
Weakness of proximal muscles, especially shoulder girdles
Hypertrophy of leg muscles
Joint contractures
Cognition normal
Serum CK 10–50 x normal
EMG myopathic
NCS normal
Fukutin-related
protein
Fukuyama congenital muscular
dystrophyb
Onset at birth
Hypotonia, joint contractures
Generalized muscle weakness
Hypertrophy of calf muscles
Seizures, mental retardation
Cardiomyopathy
Serum CK 10–50 x normal
EMG myopathic
NCS normal
MRI shows hydrocephalus and
periventricular and frontal
hypomyelination
Fukutin
Muscle-eye-brain disease Onset at birth, hypotonia
Eye abnormalities include: progressive myopia, cataracts, and optic nerve, glaucoma,
retinal pigmentary changes
Progressive muscle weakness
Joint contractures
Seizures, mental retardation
Serum CK 5–20 x normal
MRI shows hydrocephalus,
cobblestone lissencephaly,
corpus callosum and cerebellar
hypoplasia, cerebral
hypomyelination
N-acetyl-
glucosaminyl
transferase
(POMGnT1)
Walker-Warburg syndromeb Onset at birth, hypotonia
Generalized muscle weakness
Joint contractures
Microphthalmos, retinal dysplasia, buphthalmos, glaucoma, cataracts
Seizures, MR
Serum CK 5–20 x normal
MRI shows cobblestone
lissencephaly, hydrocephalus,
encephalocele, absent corpus
callosum
O-mannoxyl-
transferase-
1(POMT1)

28. Myotonic dystrophy
• Also called dystrophia myotonica.
• Two types: myotonic dystrophy type 1 (DM1) and
myotonic dystrophy type 2 (DM2).
Clinical features:
• Hatchet-faced – temporalis, masseter & facial muscle
weakness.
• Frontal baldness is characteristic.
• Neck muscles, including flexors and
sternocleidomastoids, and distal limb muscles are
involved early.
• Proximal muscles are spared throughout the course of
the disease

29. • Diaphragm & intercostal muscles involvement causes
respiratory insufficiency.
• Myotonia usually appears by 5 years, demonstrated
by percussion of thenar eminence, tongue and wrist
extensor muscles.
• Cardiac involvement- 1st degree heart block,
complete heart block & sudden death, CCF & MVP
may also occur.
• Other associated features include intellectual
impairment, hypersomnia, posterior subcapsular
cataracts, gonadal atrophy, insulin resistance, and
decreased esophageal and colonic motility.

30. • Laboratory features: Diagnosis is usually
clinical.
• S.CK may be normal or raised.
• Muscle biopsy shows muscle atrophy.
Typically, numerous internalized nuclei can be
seen in individual muscle fibers as well as
atrophic fibers with pyknotic nuclear clumps.
• EMG shows myotonia.
• Treatment: DM1 rarely requires treatment.
Patients with DM2 requires phenytoin.
• Pace makers may be required for heart blocks.

31. Congenital myopathies

32. Central core disease
• Autosomal dominant.
• Decreased foetal
movements and breech
presentations.
• Hypotonia & delay in motor
milestones.
• In late childhood difficulty
in climbing stairs, running.
• O/E- Mild neck muscle,
proximal muscle weakness
present.
• CDH, scoliosis, pes cavus
and CTEV may also occur.
• Non progressive with
exceptions.
• Malignant hyperthermia
risk is common.
• Lab findings: S.CK- normal.
• EMG myopathic pattern.
• Muscle biopsy shows fibers
with single or multiple
central or eccentric discrete
zones (cores) devoid of
oxidative enzymes.
• No specific treatment.

33. Nemaline myopathy
• Nema in Greek means thread.
• Presence in muscle fibers of
rods or threadlike structures.
• Severe neonatal form presents
with hypotonia and feeding
and respiratory difficulties,
leading to early death.
• Usually presents in infancy or
childhood with delayed motor
milestones. The disease is
either non progressive or
slowly progressive.
• The long, narrow facies, high-
arched palate, and open-
mouthed appearance due to a
prognathous jaw.
• Pectus excavatum,
kyphoscoliosis, pes cavus, and
clubfoot deformities.
• Lab features: S.CK- normal or
slightly raised.
• EMG- myopathic.
• Muscle biopsy.
• No specific treatment.

34. Centronuclear (Myotubular) Myopathy
• Three variants:
• A neonatal form presents with
severe hypotonia and weakness
at birth.
• The late infancy–early childhood
form presents with delayed
motor milestones.
• Later, difficulty with running and
stair climbing
• A marfanoid, slender body
habitus, long narrow face, and
high-arched palate are typical.
• Progressive external
ophthalmoplegia with ptosis and
varying degrees of extraocular
muscle impairment are
characteristic of both the
neonatal and the late-infantile
forms.
• The late childhood–adult form,
has an onset in the second or
third decade. Patients have full
extraocular muscle movements
and rarely exhibit ptosis.
• Normal or slightly elevated CK
levels
• EMG is myopathic.
• Muscle biopsy specimens in
longitudinal section demonstrate
rows of central nuclei, often
surrounded by a halo. In
transverse sections, central nuclei
are found in 25–80% of muscle
fibers.
• No specific treatment is available

35. Hypokalemic Periodic Paralysis (HypoKPP)
• HypoKPP type1 & type 2
• Calcium channel disorder
• Onset at adolescent
• Men are more affected than
women
• Attacks are often provoked
by meals high in
carbohydrates or sodium
and may accompany rest
following prolonged
exercise
• Weakness takes >24hrs to
resolve.
• Respiratory muscles are
usually spared
• Lab diagnosis: A low serum
potassium level during an
attack, excluding secondary
causes, establishes the
diagnosis.
• Interattack muscle biopsies
show the presence of single
or multiple centrally placed
vacuoles or tubular
aggregates.
• Treatment: Oral KCl (0.2–
0.4 mmol/kg) should be
given every 30 min. Rarely
IV KCl is required.
• Mannitol is the preferred
vehicle for administration of
IV potassium

36. Hyperkalemic Periodic Paralysis (HyperKPP)
• Misnomer as patients will be
normokalemic
• Mutations of the voltage-
gated sodium channel SCN4A
gene
• Onset is in the first decade
• Potassium administration
precipitates attacks
• Onset in first decade
• Attacks are brief and mild,
usually lasting 30 min to 4 h.
• Weakness affects proximal
muscles.
• Attacks are precipitated by rest
following exercise and fasting.
• Lab features: Potassium
usually will be normal.
• EMG shows reduced
amplitude.
• The EMG will often
demonstrate myotonic
discharges during and
between attacks.
• The muscle biopsy shows
vacuoles that are smaller, less
numerous, and more
peripheral
• Acetazolamide (125–1000
mg/d) is helpful.

37. Paramyotonia Congenita
• Autosomal dominant
condition; voltage-gated
sodium channel mutations
• Attacks of weakness are cold-
induced or occur
spontaneously and are mild
• Myotonia is a prominent
feature but worsens with
muscle activity (paradoxical
myotonia).
• Over time patients develop
interattack weakness as they
do in other forms of periodic
paralysis.
• Serum CK is usually mildly
elevated. Routine sensory and
motor nerve conduction
studies are normal.
• Patient is either normo or
hyperkalemic.
• Thiazide diuretics (e.g.,
chlorothiazide, 250–1000
mg/d) and mexiletine (slowly
increase dose from 450 mg/d)
are reported to be helpful.
Patients should be advised to
increase carbohydrates in their
diet.

38. Drug induced myopathies
Drugs Major Toxic Reaction
Lipid-lowering agents
Fibric acid derivatives
HMG-CoA reductase inhibitors
Niacin (nicotinic acid)
Drugs belonging to all three of the major classes of lipid-lowering agents can produce a
spectrum of toxicity: asymptomatic serum creatine kinase elevation, myalgias, exercised-
induced pain, rhabdomyolysis, and myoglobinuria.
Glucocorticoids Acute, high-dose glucocorticoid treatment can cause acute quadriplegic myopathy. These high
doses of steroids are often combined with nondepolarizing neuromuscular blocking agents
but the weakness can occur without their use. Chronic steroid administration produces
predominantly proximal weakness.
Nondepolarizing neuromuscular blocking
agents
Acute quadriplegic myopathy can occur with or without concomitant glucocorticoids.
Zidovudine Mitochondrial myopathy with ragged red fibers.
Drugs of abuse
Alcohol
Amphetamines
Cocaine
Heroin
Phencyclidine
Meperidine
All drugs in this group can lead to widespread muscle breakdown, rhabdomyolysis, and
myoglobinuria.
Local injections cause muscle necrosis, skin induration, and limb contractures.
Autoimmune toxic myopathy
D-Penicillamine
Use of this drug may cause polymyositis and myasthenia gravis.
Amphophilic cationic drugs
Amiodarone
Chloroquine
Hydroxychloroquine
All amphophilic drugs have the potential to produce painless, proximal weakness associated
with autophagic vacuoles in the muscle biopsy.
Antimicrotubular drugs
Colchicine
This drug produces painless, proximal weakness especially in the setting of renal failure.
Muscle biopsy shows autophagic vacuoles.

39. Other myopathies
• Glycogen Storage and Glycolytic Defects
• Carnitine Palmitoyltransferase Deficiency
• Mitochondrial Myopathies
-Progressive External Ophthalmoplegia
Syndromes with Ragged Red Fibers.
- Kearns-Sayre Syndrome (KSS)
- Autosomal Recessive Cardiomyopathy and
Ophthalmoplegia (ARCO)
- Mitochondrial Myopathy, Encephalopathy,
Lactic Acidosis, and Stroke-Like Episodes (MELAS)

40. • Thyroid disorders
• Adrenal disorders
• Pituitary disorders
• Diabetes mellitus
• Vitamin K deficiency
• Myopathy of systemic illness
• Drugs of Abuse and Related Myopathies
• Drug-Induced Autoimmune Myopathies

41. References
• Harrison's Principle of Internal Medicine 19th
Edition