APPROCH TO A CASE OF MYOPATHY

Introduction:
• Myopathies constitute genetic and acquired diseases of skeletal muscle.
• Characterised  by  muscle weakness and wasting for which primary pathology lies in
muscle itself.
• Myopathy simply means muscle disease i.e .Implying primary disease is within muscle
(not nerve or brain)
• Distribution of muscle weakness depends upon the type of the disease
• Majority involve proximal muscles i.e. limb girdles
• Inherited type is often incurable
• Inflammatory, metabolic types often treatable.
Classification and causes of Myopathies:


APPROCH TO A CASE OF MYOPATHY
Introduction:
• Myopathies constitute genetic and acquired diseases of skeletal muscle.
• Characterised  by  muscle weakness and wasting for which primary pathology lies in
muscle itself.
• Myopathy simply means muscle disease i.e .Implying primary disease is within muscle
(not nerve or brain)
• Distribution of muscle weakness depends upon the type of the disease
• Majority involve proximal muscles i.e. limb girdles
• Inherited type is often incurable
• Inflammatory, metabolic types often treatable.
Classification and causes of Myopathies:

Myopathy can be genetically inherited, or result from endocrine defects, immunological or
other causes.
I. Inherited Myopathies
I. Muscular dystrophies
ii. Inherited biochemical defects causing muscle weakness.
i.
 Muscular dystrophies:
Are due to genetic defects but actual pathogenesis not clear.
Duchenne ,Becker      ---                 X linked recessive gene.
Dystrophia myotonica --                  Autosomal Dominant gene
Facio-scapulo-humeral --                Autosomal dominant gene
Limb girdle --                                   Variable inheritance (not of single entity)
Others:Congenital myopathy
Oculopharyngeal
Distal myopathy
           ii. Inherited metabolic defects causing Myopathies
• Specific enzyme deficiencies disrupt pathway of carbohydrate or fat
metabolism with-accumulation of substrate within muscle cells.
• Enzyme deficiency can be within muscle cytoplasm or
      mitochondria-the cellular powerhouse. (Mitochondrial myopathy
      classical e.g. Kearns-Sayer syndrome)
• Can affect utilization of glycogen/glucose
• Or block metabolism of pyruvates/fatty acids
• In some types uncoupling of excitation -contraction occurs
e.g. McArdles syndrome
• Malignant hyperpyrexia- Sustained muscle contraction in absence      
of nerve stimulation. No muscle weakness. But after general
              anesthesia severe muscle spasm, hyperpyrexia death in 50%.
                                                     Pathogenesis: Defective Calcium metabolism, allowing anesthetic
- to massively raise  calcium in muscle with sustained muscle  
              contrction and necrosis which causes hyperpyrexia.
II. Acquired Myopathies
A. Immunologically mediated
B. Non inflammatory myopathies
c.   Toxic and cachectic myopathies

A.Immunologically mediated (immune system attacking muscle components)
 Polymyositis
Dermato myositis
Rarer types:
                           Inclusion body myositis
                           Those associated with collagen vascular diseases,
                         

B. Non inflammatory myopathies
Thyrotoxicosis
Hypothyroid
Cushing
Electrolyte disturbances: hypercalcemia, hypokalemia
C. Toxic and cachectic myopathies
Acute alcoholic myopathy with myoglobinuria
Steroid induced
Zidovudine induced
Clofibrate induced
Carcinomatous myopathy
Protein malnutrition

Clinical features of myopathy:
History:
Ask for symptoms  of myopathy mentioned below and
• It is important to ask for age of onset,rate of progression
• Ask for myotonia(inability to release the grip.)
• For D/D elicit h/o dysphagia(polymyositis) or diurnal variations(myasthenia)
• Family history. A proper pedigree analysis is essential
• Elicit history of delayed milestones

Symptoms:
• Muscle weakness and rapid fatigue on using the affected muscles
• Mainly  proximal muscle weakness; muscles around shoulder ,hip ,large muscles in neck
• manifesting as
Difficulty in climbing stairs, walking, running, getting out of chair
Difficulty in lifting heavy objects above the head
• H/o climbing on one’s own body
• Frequent buckling of knee or drop foot,h/o of falling/waddling
• Dysarthria, dysphagia, dyspnea, drooping of neck due to muscle weakness
• Muscle cramps,  stiffness, myoglobinuria(myoglobin- fuel for muscles)

.
Clinical presentation:
1. Muscle weakness, wasting affecting limb girdle and proximal limb muscles.
2.Exceptions-
(Coexisting distal weakness sometimes predominant in Myotonic dystrophy or inclusion
body myositis.)
     Proximal muscle weakness can also occur in certain ‘Neurogenic’ diseases.)
3. Pseudo muscular hypertrophy of calf muscles seen in Duchenne.
4. Weakness in most myopathies is symmetrical
Pseudo hypetrophy involves
Infraspinati,glutei,calf muscles,quadriceps ,deltoid; most commonly calf muscles
Gowers sign:Trying to climb up himself using  his hands while getting up from floor
Other signs
Waddling gait,
lumbar lordosis secondary to toe walking.

Note:
weakness is gradual and symmetrical
No associated sensory changes
Bowel and bladder functions are not affected.
The weakness is painless

Under Clinical Examination look for:
Ability to raise from sitting posture, Gowers sign
Ability to walk
Muscle wasting /weakness, its distribution
Deep tendon reflexes
Myotonia -inability of muscle to relax after contraction
In addition look for
Distribution of weakness
General/focal
General
Symmetry>Asymmetry
Proximal>distal
Lower limbs>upper limbs

Myopathic patient presents with the following findings

• Proximal limb  strength;is more impaired than distal except in myotonic dystrophy
Check deltoids (shoulder) and iliopsoas(hip)
Differentials
Weakness is distal in neuropathies
In Gullain Barre-weakness can be proximal but there are areflexia,sensory symptoms
and raised CSF proteins
• Neck flexion is much weaker than neck extension
• Reflexes are preserved slightly decreased except in late stages
• Sensation is unimpaired

Points which help to distinguish one myopathy from another
Fascio scapula humeral type- facial weakness present
Fatiguability-especially of extra ocular movements
Almost all patients with myasthenia gravis have ptosis or diplopia at one point of time or
another.
In Limb girdle dystrophy –pelvis and thigh muscles are involved more than head and
shoulders
Check for myotonia by percussing the thenar eminence or the tongue and check for lid
myotonia by having the patient shut his eyes tightly and then quickly open them.
Patients with myotonia are unable to let go after hand shake.
 Under general examination look for -:
Endocrine abnormalities
Cardiac abnormalities
Mental dysfunction
Specific pattern of muscle weakness as in myotonia dystrophica
Skin rash as in dermatomyositis
Cotractures
Laboratory Tests:
i.Creatinine Kinase Activity:
if elevated denotes muscle damage/necrosis
Very high values(50-100 times the the normal range) in – Duchenne,and some metabolic
myopathies
CK elevation absent or only modest in some types: - dermatomyositis, steroid myopathy.
Ck levels decline late in the disease(loss of muscle mass)
Other enzymes:
i.Lactic dehydrogenase (LDH),SGOT aldolase
Pyruvate kinase
K level –helps to diagnose periodic paralysis
ii. Electromyography and nerve conduction Studies:
Usually confirm diagnosis; exclude motor unit disease; may show if the myopathy is
inflammatory.
iii. Muscle Biopsy: Gives conclusive evidence: Can show precise nature of
the disease for which
Special  histochemical, immunochemical analysis, electron microscopic studies are  –needed.
iv. Analysis of molecular genetics: of- blood cells,muscle tissue,cultured
muscle cells. Detects prenatal disease,carriers.
v.Muscle imaging by immunocytochemical staining
vi. ECG,ECHO Cardiography
vii.Cardiac MRI and Gadoliniumenhancement(new non invasive techniques)
viii. Magnetic resonant spectroscopy
ix. Investigations for endocrine diseases as indicated.
x. Test for myositis specific antibodies
xi. CSF analysis-in myopathy-normal including protein level
Complications:
I. Cardiomyopathy, ,cardiac failure, Arrhythmias
II.Respiratory muscle involvement with breathing difficulties/respiratory failure./increased
risk of respiratory infection
III. Pharyngeal muscle weakness –risk of aspiration
IV. Joint contractures
V. Chest deformity and
VI. progressive scoliosis(asymmetric atrophy of para spinal muscles) impairs pulmonary
functions
 Causes of death
Pulmonary infection
Aspiration pneumonia
Cardiomyopathy,cardiac arrhythmias
Acute gastric dilatation(smooth muscle dysfunction)


Principles of Treatment:  treatment depends upon type and specific causes.
1. Supportive and symptomatic therapy
2. Drug therapy like  immunosuppressive for some.
3. Physiotherapy
4.Bracing to support weak muscles
5. Avoiding overexerting of muscles especially in metabolic myopathies
6.Surgery.
7.Genetic counseling in couple with X linked form of myopathy may benefit from
Preimplantation  Genetic diagnosis(PGD).When disorder is predominant in one gender
Implantation of gender specific embryo through PGD will reduce chance of having affected
child.
8.Under  research -gene therapy(delivering dystrophin  genes to muscles)
9.Under  research -cellular therapy Myoblast transplantation,stem cell transplantation)
(No favourable results seen so far)

Curable Myopathies
Drug induced-Steroids, Zidavudin
Endocrine myopathies

Drug therapy:
1.For Dermato myositis and polymyositis- following( singly or in combination: )
Glucocorticoids, azathioprine, cyclophosphamide, methotrexate, cyclosporine, high
dose immunoglobulin
2. In Duchenne -oral predinisolone or deflazacort

TO MAKE OUT TREATABLE MYOPATHY AND SOME DIFFERENTIALS

CHECK THE FOLLOWING
1. Thyroid myopathy(hyper andhypothyroidism)
2. .Steroid myopathy-has the patient been on steroids for another disorder?
Fluorinatated steroids are especially prone to cause steroid induced myopathy.
Does he have cushingsdisease?
3.Idiopathic polymyositis
ESR usually raised;evidence of other connective tissue disease may be present like dermato
myositis,rheumatoid or lupus.
4.Poly myositis associated with malignancy
Patients  may  have polymyositis symptoms as remote effect of cancer.
Poly myositis may also be associated with Sarcoidosis.
5.Alcoholic  myopathy
Check for h/o alcoholism;look for associated  cardiac myopathy.
6.Periodic paralysis
Attacks often related to cold,food and exercise
Check serum potassium level during an attack.
7.Poly myalgia rheumatica
Not associated with muscle weakness
But c/o muscle and joint pain
ESR is elevated.
This disorder is highly responsive to  steroids.
8.Myasthenia gravis
h/o fluctuating weakness during the day.
Tensilon test  -confirmative  
Tmt- Anticholinesterase,
Prednisolone,thymectomy,  plasmapheresis etc.            
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