L6: Myopathy Flashcards
Skeletal muscle constitutes the principal organ of locomotion.
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There is more than 600 separate muscles, this tissue makes up as much as 40% of the weight of adult human beings.
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- The muscle fibers are attached at their ends to tendon fibers —-> connect with the skeleton.
- By this means, muscle contraction maintains posture and produce movement.
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Histology of Muscle Fibers
- Types of Muscles
Red and White (human muscles are composed of both types)
Histology of Muscle Fibers
- Each lower motor neuron supplies a bundle of muscle fibers but each M.F. is innervated by only one axon.
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Def of Motor Unit
is a motor neuron and all the muscle fibers it innervates.
Examples of Motor Unit
- In Ocular muscles: a motor unit contains only 6 to 10 muscle fibers.
- In Gastrocnemius: a motor unit contains as many as 1,800 fibers
Physiology of Muscle Fibres & muscle Contraction
Manifestations of Muscle Diseases
Def of Progressive Muscular Dystrophy
- Group of genetically determined primary degenerative muscular disorders characterized by muscular weakness and wasting (myopathy).
Pathogenesis of Progressive Muscular Dystrophy
- A defect in muscle fiber plasma membrane → uncontrolled entry of calcium → activates calcium dependent protease → muscle fiber necrosis.
- The missing gene product is a protein called Dystrophin.
Pathology in Progressive Muscular Dystrophy
Classification of Progressive Muscular Dystrophy
Classification of Progressive Muscular Dystrophy
- X-Linked Recessive
- Severe (Duchenne).
- Benign (Becker).
Classification of Progressive Muscular Dystrophy
- AD
- Facio-scapulo-humeral.
- Scapulo-peroneal.
- Limb girdle.
- Distal.
- Ocular
- Oculo-pharyngeal.
Classification of Progressive Muscular Dystrophy
- Autosomal Recessive
Age in Becker Muscle Dystrophy
at 5-20 Years
Course of Becker Muscle Dystrophy
Slowly progressive and does not shorten life.
Sex in Duchenne Muscle Dystrophy
Affects Boys & Females are carriers. → due to It is X-linked s
Age in Duchenne Muscle Dystrophy
- Between 3 -10 years.
- The child appears normal at birth and in the first year of life.
Onset of Duchenne Muscle Dystrophy
Gradual
Course of Duchenne Muscle Dystrophy
Rapidly progressive
Site affected in Duchenne Muscle Dystrophy
Pelvic girdle, then Shoulder girdle muscles.
CP of Duchenne Muscle Dystrophy
CP of Duchenne Muscle Dystrophy
- Which Side?
Bilateral & Symmetrical
CP of Duchenne Muscle Dystrophy
- Proximal or Distal?
Proximal more than distal
CP of Duchenne Muscle Dystrophy
- Symptoms
- Slow Walking, inability to Run, frequent Falling.
- Difficulty in Climbing stairs, Putting on and Taking off clothes.
CP of Duchenne Muscle Dystrophy
- Shoulders
Sloping shoulders
CP of Duchenne Muscle Dystrophy
- Scapulae
Winging of scapulae
CP of Duchenne Muscle Dystrophy
- Spine & pelvis
- Exaggerated Lumbar Lordosis, protuberant abdomen, pelvis is tilted forward due to: Weak Glutei, so lordosis compensates this tilting and it disappears with sitting.
CP of Duchenne Muscle Dystrophy
- Muscle Hypertrophy?
CP of Duchenne Muscle Dystrophy
- Gait
CP of Duchenne Muscle Dystrophy
- Signs
CP of Duchenne Muscle Dystrophy
- Ambulation
Ambulation is lost at age of about 10 years.
CP of Duchenne Muscle Dystrophy
- Reflexes
Reflexes are lost → With increasing weakness and progressive muscle atrophy
CP of Duchenne Muscle Dystrophy
- No …….
No fasciculations, sphincter disturbance, sensory changes.
CP of Duchenne Muscle Dystrophy
- which Muscles are involved?
CP of Duchenne Muscle Dystrophy
- Speech
Delayed speech: development may occur.
CP of Duchenne Muscle Dystrophy
- IQ
May be affected
Age in Facio-Scapulo-Humeral Type
starts in the 2nd decade
Course in Facio-Scapulo-Humeral Type
Benign, arrest is common.
Incidence of Facio-Scapulo-Humeral Type
Females are less severely affected than males.
CP of Facio-Scapulo-Humeral Type
CP of Facio-Scapulo-Humeral Type
- Transverse Smile
Elevators > Retractors
Incidence of Scapulo-Peroneal Type
Rare Syndrome
CP of Scapulo-Peroneal Type
Like Facioscapulohumeral but with no facial affection.
Inheritance of Limb-Girdle Ms Dystrophy
- Autosomal recessive in 90%,
- Autosomal dominant in 10%.
- Sporadic cases were reported
Age in Limb-Girdle Ms Dystrophy
Starts at 3rd Decade
Course of Limb-Girdle Ms Dystrophy
Slowly Progressive
CP of Limb-Girdle Ms Dystrophy
- More commonly starts in Shoulder Girdle more than Pelvic Girdle
- There may be enlarged calf muscles mildly.
- Usually limited for years before spread
- Severe disability occurs after about 20 years.
Inheritance of Congenital Type Ms Dystrophy
Autosomal recessive
CP of Congenital Type Ms Dystrophy
- Characterized by congenital or early infantile onset of weakness with variable CNS involvement including ocular.
- Epilepsy is common and although mental development is normal,
MRI in Congenital Type Ms Dystrophy
white matter abnormalities
Inheritance of Distal Myopathy
Some Are Autosomal Dominant & Some Are Autosomal Recessive
Onset of Distal Myopathy
- Some begin in 4th - 6th decade
- Some patients show onset in childhood or early adult life-
Age in Occular Type Ms Dystophy
Before 30 years
CP of Occular Type Ms Dystophy
- External opthalmoplegia,
- Progressive bilateral ptosis
- Orbicularis oculi affection.
- No pupillary changes
- No diplopia (gradual bilateral symmetrical affection).
Age in Occulo-Pharyngeal Type
Around 40 years old.
CP of Occulo-Pharyngeal Type
Similar to ocular type but with dysphagia.
Investigations in Progressive Muscular Dystrophy
Investigations in Progressive Muscular Dystrophy
- EMG
Diminished duration and amplitude of motor action potential.
Investigations in Progressive Muscular Dystrophy
- Urine
- Diminished creatinine
- Appearance of creatine.
Investigations in Progressive Muscular Dystrophy
- Serum Enzymes
Increase and that’s used to detect
- Female carriers and
- Preclinical diagnosis in males.
Investigations in Progressive Muscular Dystrophy
- Muscle Bx
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TTT of Progressive Ms Dystophy
TTT of Progressive Ms Dystophy
- Steroids
It is now accepted that it prolongs ambulation
TTT of Progressive Ms Dystophy
- Myoblast Transfer
Injecting the muscle with a huge number of myoblasts will give a transient improvement (but cost exceeds benefit).
Def of Myotonic Disorders
A group of M. disorders characterized by delayed relaxation of skeletal muscles after voluntary, mechanical or electrical stimulation.
What Improves Myotonic Disorders?
- Exercise (Repetition of movement)
- Calcium
- Warmth
- Quinine and Procainamide.
What Worsens Myotonic Disorders?
- Rest
- Cold
- Potassium
- Prostigmine.
Types of Myotonic Disorders
- Myotonic Dystrophy
- Myotonia congenita
- Paramyotonia congenita
- Myotonia paradoxica
- Acquired myotonia
- Chondrodystrophic myotonia (Schwartz-Jample syndrome)
Age in Myotonic Dystrophy
20 - 50 Years
Incidence in Myotonic Dystrophy
Male › female
CP of Myotonic Dystrophy
Age in Myotonia Congenita
1st & 2nd Decade
Incidence of Myotonia Congenita
- Female more than male.
- Autosomal recessive & less frequently autosomal dominant
CP of Myotonia Congenita
- Present since birth (Difficult Suckling).
- Generalized muscular hypertrophy and stiffness.
PPT Factors for Paramyotonia Congenita & Myotonia Paradoxica
- Precipitated only by exposure to cold
- Exacerbated by exercise
Acquired Myotonia is associated with …..
Occurs with polymyositis and some cases of polyneuropathy.
Another Name of Chondrodystrophic Myotonia
Schwartz-Jample Syndrome
CP of Chondrodystrophic Myotonia
- AR
- Dwarfism
- Myotonia
- Skeletal deformities
Prognosis of Myotonic Disorders
Prognosis of Myotonic Disorders
- Myotonia Congenita
Prognosis of Myotonic Disorders
- Myotonia Dystrophica
Prognosis of Myotonic Disorders with anasethia
TTT of Myotonic Disorders
TTT of Myotonic Disorders
- Genetic Counseling
- Female carrying the gene may be asymptomatic but still at risk of having a child with sever congenital form of the disease so antenatal diagnosis based on chorionic villus sampling is needed.
TTT of Myotonic Disorders
- ECG
regular
TTT of Myotonic Disorders
- Chest Infections
may be reduced by influenza and pneumococcus vaccination.
TTT of Myotonic Disorders
- Anesthetia
The patient must carry a warning card explaining hazards.
TTT of Myotonic Disorders
- Cataract
Treated surgically.
TTT of Myotonic Disorders
- Drugs
- Procainamide (500 mg t.d.s.) & Phenytoin (100 mg t.d.s.)
- They are theoretically contraindicated because of their potential action on cardiac conduction but practically few problems have been reported.
TTT of Myotonic Disorders
- Speech therapy
to correct swallowing and dysarthria.
Def of Myasthenia Gravis
- Disorder of transmission of the myoneural junction characterized clinically by fatigability on repetition of muscular activity which may be relieved by rest and or cholinergic drugs.
Pathogenesis of Myasthenia Gravis
It is due to an autoimmune process in which antibodies against acetylcholine receptors cause a disordered conduction in neuromuscular junction.
Pathology of Myasthenia Gravis
Sex in Myasthenia Gravis
Female: male = 2: 1
Age in Myasthenia Gravis
Mean age of onset: 26y in Females, 30y in Males.
Myasthenia Gravis is closely related to ……
- Thyrotoxicosis
- Rheumatoid arthritis
- M.S. (Multiple sclerosis)
- SLE. (Systemic Lupus Erythematosus)
- Biliary cirrhosis
- Cancer
CP of Myasthenia Gravis
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Onset of Myasthenia Gravis
Gradual
Course of Myasthenia Gravis
progressive with remissions.
CP of Myasthenia Gravis
- site
Only skeletal muscles (smooth muscles are not involved).
CP of Myasthenia Gravis
- Symptoms
CP of Myasthenia Gravis
- Descending march
CP of Myasthenia Gravis
- Fluctiations in Myasthenia
CP of Myasthenia Gravis
- Muscle Bulk Affection
No
CP of Myasthenia Gravis
- smooth Musce affection
No
CP of Myasthenia Gravis
- Smile?
Retractors of mouth angle › elevators → Vertical or snarling smile.
What induces remission of Myasthenia Gravis?
Pregnancy
Dx of Myasthenia Gravis
Dx of Myasthenia Gravis
- Clinical Fatigue Test
Inducing fatigue by asking the patient to:
- Count to 50 (will induce dysarthria) or
- Maintain looking up (will precipitate ptosis).
Dx of Myasthenia Gravis
- Prostigmine test
1.5 mg Prostigmine + 0.5 mg Atropine IM → Improve myasthenia.
Dx of Myasthenia Gravis
- EMG
Repetitive stimulation test shows:
- Diminished amplitude after repeated stimulation (decremental response).
Dx of Myasthenia Gravis
- Tensilon Test
2 mg IV followed, if no idiosyncrasy, by 8mg → improve myasthenia after a minute.
Dx of Myasthenia Gravis
- Most Sensitive Test
Detection of Anti-Ach R Antibodies
Dx of Myasthenia Gravis
- Chest tomogram
to detect Thymoma or Thymic Hyperplasia.
Dx of Myasthenia Gravis
- Thyroid Function Tests
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Dx of Myasthenia Gravis
- tests for Collagen Disorders or Cx
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TTT of Myasthenia Gravis
TTT of Myasthenia Gravis
- Anticholinestrase
- Mestinon
- Prostigmine: titrate until adequate response.
TTT of Myasthenia Gravis
- Prednisone
- 50 mg daily then taper to 5-10 mg per day as a maintenance dose.
TTT of Myasthenia Gravis
- Azathioprine
2mg/ Kg/day.
TTT of Myasthenia Gravis
- Plasmapharesis
to get rid of harmful antibodies.
TTT of Myasthenia Gravis
- IVIG
0.4 gm/ Kg/day divided over five successive days.
TTT of Myasthenia Gravis
- Thymectomy
Obligatory for Thymoma or Thymic hyperplasia.
Def of Crises in Myasthnia
Severe deterioration in a myasthenic patient which necessitate Mechanical Ventilation.
Types of Crises in Myasthnia
Types of Crises in Myasthnia
- Myasthenic Crises
Types of Crises in Myasthnia
- Cholinergic Crises
Managment of Crises
Managment of Crises
- Tensilon test
For differentiation (it will improve only the myasthenic crisis)
Managment of Crises
- Avoid ……
- Aminoglycosides
- Ampicillin
- Phenytoins
- Propranolol
- Morphine
- Barbiturates (has a neuromuscular blocking effect)
Managment of Crises
- Re-introduction of Drugs
age in Neonatal Myasthenia
Seen in infants from a myasthenic mother
Etioogy of Neonatal Myasthenia
It is due to antibodies from the mother serum.
TTT of Neonatal Myasthenia
- Recovers spontaneously (1 week - 3 months after delivery).
- The infant need treatment with anti cholinesterase for short duration
Def of Congenital Myasthenia
Genetically determined non-auto-immune disorder.
Pathogenesis of Congenital Myasthenia
- Mutation affecting one of A.Ch.R. subunits
- Mutation affecting the end plate protein.
Incidence of Congenital Myasthenia
- Rare disease
- Begin in infancy (floppy infant).
CP of Congenital Myasthenia
Etiology of Lambert-Eaton Syndrome (Myasthenic-Myopathic)
CP of Lambert-Eaton Syndrome (Myasthenic-Myopathic)
TTT of Lambert-Eaton Syndrome (Myasthenic-Myopathic)
- Tumour treatment often improves the picture.
- Prednisolone and azathioprine often induces remission → In absence of tumor
- Plasma exchange and IVIG are effective.
