Amazing presentation

1. - Muscle Diseases
- Neuromuscular Junction disorders.
 Prof. Dr. Hazem M. Marouf

2. Myopathies
 Myopathies are disorders that adversely affect
muscle function

3. Classification
 Inherited
 Congenital myopathies
 Muscle dystrophy without myotonia or with
myotonia
 Glycogen and lipid storage disease
 Mitochondrial disease
 Channelopathies and periodic paralysis (hypo or
hyperkalaemic and paramyotonia)
 *channelopathies are genetically determined
disorders of muscle fiber membrane ion
channels.

4. Muscle fibers in glycogen storage myopathy

5. Muscle fibers in Lipid Storage myopathy
Carnitine Deficiency (Oil Red O)

6. Mitochondria Myopathy
(RRF)

7. Classifiation
 Acquired
 Inflammatory/ immune-mediated : myositis,
dermatomyositis and inclusion body
myopathies.
 Endocrinal: adrenal, thyroid and parathyroid.
 Metabolic: Hypokalemia and asteomalacia.
 Systemic: paraneoplastic and critical illness
myopathy.
 Infection: viral, bacterial…..
 Toxic: Alcohol and drugs as corticosteroids,
chloroquine, chlofibrate, emetine, colchicines,
lithium, vincristine, aminocaproic acid,
Rifampin, zidovudine…

8. Muscular Dystrophies
 These are genetically determined
chronic myopathies with progressive
course and characteristic dystrophic
histological profile (myofibril
degeneration, regeneration and
fibrosis)

10. Types of MD
 Without myotonia
 Dystrophinopathies (x-linked)
 Duchenne
 Becker
 Non dystrophinopathies
 X-linked: emery dreifuss
 Other types
 Limb girdle
 facio-scapulo-humeral
 scapuloperoneal
 oculopharengeal
 distal
 congenital muscular dystrophies
 With myotonia : myotonic muscular dystrophy

11. Duchenne Muscular Dystrophy
 Inheritance: x-linked recessive
dystrophinopathy
 Age: early childhood 3-5 years

13. (DMD) Clinically:
 Proximal weakness with difficulty in walking, frequent
falls, difficulty in getting upstairs , difficulty in getting
up from the floor (Gowers’ sign)
 Later on, weakness starts to affect pelvic girdle -
leading to frequent falls- and eventually the shoulder
girdle with difficulty in shoulder raising.
 calf muscle hypertrophy (pseudohypertrophy),
 Heel cord shortening and tip toe walking.
 Compensatory lordosis (dt weak hip extensors)
 Waddling gate (dt weak hip adductors)
 Blunted intellect.

14. DMD
Gower’s Sign
Calf
pseudohypertro
phy and
contracture of
tendoachillis

15. DMD, clinically
 ON EXAMINATION:
 Muscle of the face, hands and feet are not
affected.
 Certain muscles show pseudo-hypertrophy as
calf, glutei & deltoid
 Atrophy of bicepses, triceps and folds of the
axilla.
 Diminished or absent deep reflexes but the
ankle jerk is preserved till later stage.
 Normal superficial reflexes, sphincters and
sensory system.

16. DMD: Lumbar lordosis
Exaggerated lordosis of the lumbar curvature

18. Pseudohypertrophic Calf
muscles

19. DMD
 The course is progressive till the
patient becomes wheelchair
dependant by mid-adolescence.
 Associated cardiomyopathy with
arrhythmia and CHF.
 Smooth muscle involvement with
ileus or gastric atony.
 Respiratory complications in the 3rd
decade  death.

20. Diagnosis:
 Abnormal serum levels of dystrophin.
 Elevated serum CPK.
 Serum DNA analysis (deletion, duplication
and point mutation).
 EMG : myopathic pattern.
 Muscle biopsy for dystrophin immuno-
staining to demonstrate that most fibers
are devoid of dystrophin.
 Also female carriers have an asymptomatic
elevated CK level

22. Treatment:
 Encourage the child to maintain an
active life to prevent contractures
 Orthopedic management &
physiotherapy
 Long term corticosteroid therapy may
ameliorate the course (for a short
period)
 Genetic counseling.

23. Becker Muscular Dystrophy
(BMD)
 X-linked dystrophinopathy
 Age of onset: late 1st or early
second decade

24. Clinically:
 Presents by difficulty in walking, later
on, shoulder girdle weakness occurs
with a slowly progressive course.
 Intellectual functions are average
 Cardiomyopathy is more common.
 CK may increase later in their 20s
 Longer life expectancy than DMD

25. Diagnosis

26. Emery-Dreifuss MD
 Non-dystrophinopathy.
 x-linked MD
 humero-peroneal pattern of weakness
(elbow flexion & foot dorsiflexion)
 contractures (tendon Achilles, elbow foot
dorsiflexion and posterior cervical ms)
 cardiac conduction defects  arrhythmias
and stroke which could be managed by a
pacemaker

27. OTHER DYSTROPHIES
Facio-scapulo-humeral (FSHMD)
 Dominant inheritance.
 Age: 2nd decade, 10-15 years yet there
is an infantile form.
 Clinically: facial ms weakness, scapular
winging, atrophy & weakness of biceps &
triceps sparing the deltoid & forearm
muscles.
 Infantile form progresses rapidly 
wheelchair dependant by the age of 10.

28. OTHER DYSTROPHIES
Scapulo-peroneal MD
 Autosomal dominant or recessive.
 Age: 1st decade
 Presents with arm weakness later
on, foot drop. Mild disability and
normal longevity.

29. OTHER DYSTROPHIES
 Ocular & Oculo-pharyngeal MD
 Autosomal dominant inheritance.
 Age: mid to late adulthood ie; 3rd to 4th
decade.
 Presents with ptosis, dysphagia,
ophthalmoplegia & mild proximal
weakness

30. OTHER DYSTROPHIES
 Distal MD
 Autosomal dominant inheritance.
 Age: >40 years.
 Presents with wasting of muscles of
the hands and feet, wrist extensors &
dorsiflexors of the foot
 Course: slowly progressive.

31. OTHER DYSTROPHIES
Limb Girdle Muscular Dystrophy
(LGMD)
 There are various subtypes (aytosomal dominant or
recessive).
 Onset: 1st to 2nd decade (usually before the age of
20)
 Symmetric limb-girdle pattern muscle weakness
 Waisting of shoulder girdle & pelvic girdle muscle.
 Waddling gait, compensatory lordosis & +ve Gowers’
sign
 ↑ CK ranging from normal to 20 times the normal

32. Other dystrophies
 Congenital MD
 Autosomal recessive with perinatal
onset. There is hypotonia, proximal
weakness and joint contractures.

33. MYOTONIC DISORDERS
 Myotonia Dystrophica.
 Myotonia Congenita.

34. Myotonia dystrophica:
 It is a condition in which there is
marked delay of skeletal muscle
relaxation after contraction.
 Autosomal dominant inheritance.
 Age of onset: 2nd to 3rd decade.
 Both sexes are equally affected.

35. Clinically:
 Myotonia accompanies weakness and
wasting of facial muscles,
sternomastoid and distal limb
muscles.
 Associated with systemic
manifestations as: cataract, frontal
baldness, testicular atrophy, cardiac
abnormality, DM, intellectual changes
and alveolar hypoventilation.

37. Diagnosis:
 Mild ↑ serum CK.
 Electromyography: high frequency
discharge of action potential that wax
and wane in amplitude and frequency.

38. Treatment:
 Quinine sulphate 300-400 mg 3 times
daily.
 procainamide 0.5-1g 4 times per day
 phenytoin 100mg 3 times per day.

39. Myotonia congenita
 Inherited as Autosomal dominant trait
since birth.
 Characterized by generalized myotonia
without weakness
 Muscle stiffness is enhanced by cold and
inactivity and relieved by exercise.
 Muscle status shows hypertrophy

40. D.D of Muscle Dystrophy:
 other causes of myopathies.
 progressive spinal muscle atrophy (MND).
 residual poliomyelitis.
 myasthenia graves and myathenic
syndromes
 peripheral neuropathy

41. Neuromuscular Disorders
Myasthenia Gravis

42. Myasthenia Gravis
 This is an immune mediated disorder of
neuromuscular transmission
characterized by antibodies diredcted
against the post synaptic A.Ch.
receptors, manifested clinically by
muscle weakness and fatigue, with
characteristic and sometimes very
marked fluctuation of that weakness.

43. Presynaptic terminal

44. Prevlance:
 about 1 : 100,000.
 Peaks of onset are seen in 2nd and
3rd decade in females while in males
in the 5th and 6th decade.
 It may be associated with other
autoimmune diseases (10 %) as;
hyperthyroidism, Hashimoto
Thyroiditis, pernicious anaemia, SLE
& RA.

45. Etiology and Pathogenesis:
 It is an autoimmune disease mediated by
T-lymphocytes derived from the thymus
with the development of autoantibodies to
nicotinic A.Ch receptors of post synaptic
neuromuscular junction or against muscle-
specific receptor tyrosine kinase (MuSK).
 These antibodies block the binding of A.Ch
molecules to their receptors or by
triggering immune-mediated degradation of
Ach. Receptors.
 Loss of large numbers of functional ACh.
Receptors.

46. Classification according to
Osserman criteria:
 group I ocular (15-20 %)
 group IIa mild generalized (30%).
 Group IIb moderate generalized
(20%).
 Group III acute fulminating (10%).
 Group IV late sever (10%).

47. Clinical presentation:
 It may start ocular, generalized,
neonatal, congenital or may be drug
induced.

48. Cardinal symptoms include :
 Fluctuating weakness affecting extra ocular muscles,
bulbar and extremities with proximal weakness.
 Intermittent and asymmetric extra ocular muscle
affection with diplopia and ptosis.
 Soft speech with nasal tone, nasal regurgitation,
difficult chewing due to bulbar affection.
 Facial weakness with expressionless facies, vertical
smile (myasthenic snarl) and eyelid weakness and
weak mouth closure and maybe head drop.

49. Cardinal symptoms include :
 Respiratory muscle involvement with
respiratory failure.
 Fatigability is worse at the end of the day
and with exercise with transient
improvement with rest (ask the patient to
count to 100 or sustain upward gaze).
 Untreated MG or with some ppt-ing factors
as hot weather, inter-current illness.
Menstruation, pregnancy, throtoxicosis and
certain medications  myasthenic crisis
with respiratory failure.

50. D.D:
 1) Isolated cranial nerve palsies.
 2) Multiple sclerosis.
 3) Brain stem tumours.
 4) Vertebro-basilar ischemia.
 5) Multiple cranial neuropathies due
to lepto-meningeal inflammatory
disorders (sarcoidosis, TB, fungal or
carcinomatosis) … Brain MRI is
important for exclusion

51. D.D:
 6) ALS.
 7) Lambert-Eaton syndrome (pre-synaptic
dt antibodies against voltage gated calcium
channels) electrophysiology shows an
incremental EMG pattern.
 8) Miller Fissure variant of GBS.
 9) Poly-myositis.
 10) Acquired myopathies or MD.
 11) Poliomyelitis, diphtheria & botulism 
acute bulbar weakness.

52. Diagnostic approach:
 Edrophonium test (tensilon) which is an ACh inhibitor: 10
mg/ 1ml IV starting by 2 mg then 8 mg over one minute.
 ** Muscarinic side effects: asystole, bradycardia,
syncope, nausea, excessive lacrimation & salivation.
 ** Nicotinic adverse effects: cramping and fasciculation.
 ACh receptor Antibodies: +ve in 90% of paients and +ve
striated ms antibodies in 50% of patients with ocular
myasthenia.
 Muscle specific kinase antibodies.
 Electrophysiologic studies:
 EMG with repetitive motor nerve stimulation  electro-
decremental response.
 Single-fibre EMG is more sensitive.
 CT or MRI of mediastinum:
 10-15 % of MG patients have thymic tumour.

53. Management:
 ACh esterase inhibitors: pyridostegmine bromide
(mestinon) 30-60 mg every 4 to 6 hours.
 An overdose can lead to cholinergic crisis with
worsening of the condition which can be identified by
excessive salivation, lacrimation, muscle cramps,
fasciculation, ppp ….
 Corticosteroids: prednisone 60-100 mg/day for
several months eg 2-4 months with gradual tapering.
 Azathioprine 100-150 mg/day (liver function test and
WBC count must be checked periodically).

54. Management:
 Plasma exchange is indicated in the following
conditions:
 Myasthenic crisis.
 Steroid related exacerbation.
 As maintenance therapy in refractory patients to
other forms of therapy.
 Before thymectomy
 IVIG 0.4 mg/kg/day for 5 days.
 Thymectomy.
 Cyclosporine.
 Avoidance of certain medication as aminoglycosides
antibiotics, B-blockers, Ca channel blockers…

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56. Thank You