Myopathies

Aldy S. Rambe

General Considerations
Myopathy

means a primary disorder of muscle

causing wasting and/or weakness in the absence of
sensory abnormalities
Can result from a variety of inherited and acquired
disorders.
Pattern of weakness remain similar despite the
broad spectrum of etiologies.
Detailed family history, broad systemic reviews,
and careful drug history are mandatory.

ESSENTIALS of DIAGNOSIS

Weakness greater proximally than distally (myopathic

distribution)
Normal sensation
Normal sphincter function
Relative preservation of deep tendon reflexes
Muscle biopsy is often definitive
Genetic testing can confirm diagnosis of hereditary
disorders caused by specific mutations.

Muscular Dystrophies
Muscular

dystrophies are myopathies that

tend to be prgressive with ongoing
degeneration and regeneration and fatty
infiltration of muscle fibers.

DUCHENNE MUSCULAR
DYSTROPHY
The

most common muscular dystrophy

Prevalence : 1 : 3500 male births
Almost always in male, while female are carriers
X-linked recessive disorders
1st case was reported in Italy in 1836, and in 1852 was
recognized and described as an inherited disorder of
boys by the english physician Meryon.
In DMD no dystrophin is found in muscle or other
body tissue cell walls.

DMD Clinical Patterns

Typically infants with DMD are thought to have no

physical problems.
Muscle weakness is usually first recognized between ages
3 and 5 years. It progress symmetrically and linearly until
age 14, when progression slows and occurs in a predictable
pattern, with extensor muscles being weaker than flexor
muscles.
Children tend to walk on their toes from outset and may
never be able to walk with the feet flat (toe walking)

DMD Clinical Patterns (cont.c)

They also tend to waddle (waddling gait) and have to climb up
their legs, thighs and hips when getting up from the floor or from
a chair (Gowers sign).
The ability to run is not attained.
Walking velocity begins to decrease linearly between ages 4 and
6 and is about 29% of normal by age 10.
Patients developed an imbalance in muscle strength at every
joint. Flexors remain stronger extensors. This lead to
musculotendinous contractures and loss of joint range of motion.
The stronger muscles on one side of the joint stretch their weaker
antagonists cause the weaker muscles get weaker even faster
because they are no longer at their ideal length for contracting.

GOWERS SIGN

CALF PSEUDOHYPERTROPHY

TOE WALKING

Microsoft:
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DIAGNOSIS
Elevated

muscle enzymes level

:
CK, AST, ALT, LDH, aldolase
creatinuria, myoglobinuria
Abnormal ECG : tachycardia, RBBB, Q wave
Abnormal EMG : short-duration, small-amplitude
motor unit potentials with early recruitment (socalled myopathic features)
DNA analysis : mutation
Muscle biopsy

THERAPY
NO

specific treatment
Prednisone 0.75 g/kb/day significant
increase in muscle strength and prolong
ambulation up to 3 years.
Deflazacort 0.9 mg/kg/day lower side
effects
Physical therapy, bracing, orthoses, and
orthopaedic surgery are often required

Becker Muscular Dystrophy

X-linked

recessive disorder
A milder allelic form of DMD, with decreased or
altered dystrophin rather than absence.
Onset usually after 12 yearsof age, and delayed
onset after the 4th decade is occasionallly seen
Limb-girdle weakness is typical
Cardiac involvement may occur
Mental retardation is rare

Becker Muscular Dystrophy (cont.d)

Life

expectancy is reduced
Most survive into the 4th or 5th decade
The clinical approach is similar to DMD

DRUG-INDUCED MYOPATHY
Mechanism of drug-induce myopathy
Drug Mechanism
Cholesterol lowering agent
Necrosis
Costicosteroids Fiber atrophy
Diuretics
Metabolic disturbances
D-Penicillamine, L-Tryptophan
Inflammation
Emetine, amiodarone, colchicine, Vacuolar changes
and chloroquine
Vaccines adjuvants containing
Macrophagic
Aluminium hydroxide
myofasciitis
Valproic acid
Carnitine deficiency
Zidovudine
Mitochondrial dysfunction

CORTICOSTEROID MYOPATHY
ESSENTIALS of DIAGNOSIS :

Slowly progressive proximal weakness (most common)

Rapidly progressive weakness in some patients (rare)
Follows long-term treatment with corticosteroid doses
greater than 30 mg/day
Cushingoid appearance
Serum CK level is usually normal
Normal findings on EMG, or myopathic features without
spontaneous activity
Muscle biopsy evidence of type 2b fiber myopathy

CHOLESTEROL-LOWERING AGENT
MYOPATHY
Every agents including statins, niacin, clofibrate, and
gemfibrozil has myotxic effects.
ESSENTIALS of DIAGNOSIS :
Exposure

to cholesterol-lowering agents

Myalgias
Proximal

muscle weakness

CHANNELOPATHIES
Channelopathies are rare diseases caused by functional
disturbances of ion channel proteins as a result of specific
mutations. These disorders include the familial periodic
paralyses and disorders with myotonia
ESSENTIALS of DIAGNOSIS :
Inherited disorder
Weakness (episodic), myotonia, or both
Precipitating factors are usually identifiable

CHANNELOPATHIES
1. Hypokalemic periodic paralysis *
2. Hyperkalemic periodic paralysis *
3. Paramyotonia congenita *
4. Myotonia congenita (Thomsen) *
5. Generalized myotonia (Becker) **
6. Malignant Hyperthermia *
* autosomal dominant inheritance
** autosomal recessive inheritance

HYPOKALEMIC PERIODIC PARALYSIS

Type 1 Ca channel defect, type 2 Na channel defect

Onset : puberty to third decade
Clinical findings :
* episodic attacks of weakness (presence, typical
duration, severity)
* normal or mildly elevated serum CK level during
attack
* myotonia confined to eyelids
* no muscle hypertrophy

HYPOKALEMIC PERIODIC PARALYSIS

Precipitating factors : carbohydrate load, postexercise

period, pregnancy, emotional stress, cold.
Treatment :
* Potassium chloride 0,25 mEq/kg PO (may repeat
every 30 minutes until weakness subsides)
* Avoid IV potassium because of risk of uncontrollable
hyperkalemia
Prophylaxis :
* Acetazolamide ; titrate up to 3 x 250 mg/day
* Dichlorphenamide ; 3 x 25 mg/day

DISORDERS OF THE
NEUROMUSCULAR JUNCTION
Myasthenia

Gravis
Lambert-Eaton Myasthenic Syndrome
Congenital Myasthenic Syndromes
Botulism
Tick Paralysis

MYASTHENIA GRAVIS

The most common NMJ disorders

Acquired, predominantly antibody-mediated autoimmune
disease
Ab are targeted against the nicotinic AChR at NMJ
overall reduction in the number of AChR and damage to
the postsynaptic membrane
Prevalence 1 : 10.000 - 20.000 people.
Male : fifth and sixth decade
Female : second and third decade

PATHOGENESIS

In generalized MG, Ab (+) in up o 90%, in purely ocular

MG, only about 50% Ab (+)
Ab cross-link the AChRs and facilitate unusually rapid
endocytosis receptor loss on postsynaptic membrane
Complement-mediated damage to the membrane results in
fewer membrane folds and widened synaptic cleft.
The Ab production is a T-cell-mediated process thoght to
be associated with thymic dysfunction.
Thymic hyperplasia - 70% MG ; Thymoma 10% MG

ACETHYLCHOLINE SYNTHESIS

CLASSIFICATION
Group 1 : ocular myasthenia
Group 2 : mild generalized myasthenia
Group 3 : severe generalized myasthenia
Group 4 : crisis myasthenia

CLINICAL FINDINGS

Clinical characteristics : fluctuating, fatigable weakness of

commonly used muscles.
Hallmark features : ptosis, diplopia, dysarthria, dysphagia,
respiratory and limb muscles weakness.
50% presents with ocular findings.
Ocular muscles weakness usually bilateral and asymmetric
and result in ptosis, diplopia or both. The pupil is spared.
Almost all MG develop ocular symptoms, in some limited
to the extraocular muscles

Ptosis

DIAGNOSTIC STUDIES
1. Tensilon (edrophonium) test
2. Prostigmin test
3. Laboratory studies :
serologic testing : AChR-binding Ab (most sensitive)
AChR-modulating Ab
AChR-blocking Ab
4. Electrodiagnostic studies :
slow repetitive nerve stimulation
5. Imaging and other studies :
CT or MRI scan of the chest

TREATMENT
A. Symptomatic Treatment :
cholinesterase inhibitors which increase the
concentration of Ach at the AChR.
Eg. : Pyridostigmine bromide, up to 600 mg/day PO
Ambenomium, 5 25 mg PO 3-4 x/day,
max 200 mg/day
Neostigmine, up to 150 mg/day PO

TREATMENT
B. Immunosupressive Treatment :
1. Thymectomy :
* most effective during the first 2 years of disease
* should be considered at any age of MG
* necessary in neoplastic thymoma
* in patients without thymoma, thymectomy
increase the likelihood of remission
* best surgical procedure debatable

TREATMENT
2. Medical Therapy.
a. Corticosteroid : first line agent.
b. Nonsteroidal immunosuppression :
* Azathioprine
* Mycophenolate mofetil
* Cyclosporine
c. Short-term treatment :
Plasmapharesis or IVIG
induce rapid clinical improvement but have only shortterm effects