This document discusses Myasthenia Gravis (MG), a chronic autoimmune neuromuscular disease characterized by varying degrees of muscle weakness. MG is caused by autoantibodies that block neuromuscular transmission, reducing acetylcholine receptors. Symptoms include fatigable weakness of the eyes, face, neck, and limbs. Diagnosis involves tests like the Tensilon test, repetitive nerve stimulation, and antibody tests. Treatment includes anticholinesterases, immunosuppressants, plasma exchange, and sometimes thymectomy. The document also briefly discusses other myopathies and neuromuscular junction disorders like Lambert-Eaton myasthenic syndrome.

1. NEUROLOGY
Dr. Rami Abo Ali
Neurology
-
Dr.
Rami
Abo
Ali
1

2. DISEASES OF THE NEUROMUSCULAR JUNCTION
&
MYOPATHIES
Neurology
-
Dr.
Rami
Abo
Ali
2

3. DISEASES OF THE NEUROMUSCULAR
JUNCTION
 Myasthenia Gravis
3
Neurology
-
Dr.
Rami
Abo
Ali

4. MYASTHENIA GRAVIS
DEFINITION
 Myasthenia gravis is a chronic autoimmune neuromuscular
disease characterized by varying degrees of weakness of the
skeletal (voluntary) muscles of the body.
 The name myasthenia gravis, which is Latin and Greek in
origin, literally means "grave muscle weakness", as it used to
be a fatal disease before drugs development.
4
Neurology
-
Dr.
Rami
Abo
Ali

5. MYASTHENIA GRAVIS
ETIOLOGY AND PATHOLOGY:
 The underlying defect is a decrease in the number of
available acetylcholine receptors (AChRs) at
neuromuscular junctions due to an antibody-mediated
autoimmune attack.
 The disease is most commonly caused by autoantibodies
to acetylcholine receptors (anti-ACRs) in the post-
synaptic membrane of the neuromuscular junction.
 These antibodies block neuromuscular transmission and
initiate a complement-mediated inflammatory response.
 About 15% of patients (mainly those with late onset) have
a thymoma, and the majority of the remainder has
thymic follicular hyperplasia.
 Muscle-like cells within the thymus (myoid cells), which
bear AChRs on their surface, may serve as a source of
autoantigen and trigger the autoimmune reaction within
the thymus gland.
5
Neurology
-
Dr.
Rami
Abo
Ali

6. 6
Neurology
-
Dr.
Rami
Abo
Ali

7. MYASTHENIA GRAVIS
CLINICAL FEATURES
 The disease usually presents between the ages of 15 and 50
years.
 Women affected more often than men in the younger age groups
and the reverse at older ages.
 The cardinal symptom is abnormal fatigable weakness of the
muscles particularly of the ocular, neck, facial and bulbar
muscles.
 The weakness increases during repeated use and may improve
following rest or sleep.
 Worsening of symptoms towards the end of the day or following
exercise is characteristic.
 The first symptoms are usually intermittent ptosis or diplopia
 Resting of the eyelids (looking downwards) may be followed by
increased reflex elevation with up-gaze (so-called Cogan’s lid
twitch sign)
7
Neurology
-
Dr.
Rami
Abo
Ali

8. MYASTHENIA GRAVIS
CLINICAL FEATURES:
 Bulbar weakness may develop leading to difficulty in
swallowing, nasal regurgitation or aspiration of liquids or
food.
 Weakness in chewing is most noticeable after prolonged
effort, as in chewing meat.
 Patient may be unable to undertake tasks above shoulder
level, such as combing the hair, without frequent rests.
 Respiratory muscles may be involved, and respiratory
failure is not uncommon cause of death.
 If weakness of respiration becomes so severe as to require
respiratory assistance, the patient is said to be in crisis
(cholinergic or myasthenic crisis).
 Despite the muscle weakness, deep tendon reflexes are
preserved.
 There are no sensory signs or signs of involvement of the
central nervous system
8
Neurology
-
Dr.
Rami
Abo
Ali

9. MYASTHENIA GRAVIS
DIAGNOSIS AND EVALUATION
 The suspected diagnosis should always be confirmed by:
 Pharmacological test
 The intravenous injection of the short-acting
anticholinesterase edrophonium bromide (2mg
injected with a further 8 mg given half a minute
later, is a valuable diagnostic aid (the Tensilon test).
 Improvement in muscle power occurs within 30
seconds and usually persists for 2-3 minutes. but the
test is not entirely specific or sensitive
 Electrophysiological test
 Repetitive stimulation during nerve conduction
studies may show the characteristic decremental
response. 9
Neurology
-
Dr.
Rami
Abo
Ali

10. MYASTHENIA GRAVIS
DIAGNOSIS AND EVALUATION
 Immunological test
 Anti-acetylcholine receptor antibody (anti-ACRs) is
found in over 80% of cases, though less frequently in
purely ocular myasthenia (50%).
 Anti-MuSK antibodies (muscle-specific kinase
antibodies ) are found especially in AChRA-negative
patients.
 • In addition to these investigations, all patients
should have a thoracic CT to exclude thymoma, which
may not be visible on plain X-ray examination.
 • Screening for other autoimmune disorders,
particularly thyroid disease, is important.
10
Neurology
-
Dr.
Rami
Abo
Ali

11. MYASTHENIA GRAVIS
MANAGEMENT
 symptomatic
 • The duration of action of acetylcholine at
remaining receptors in the neuromuscular junctions
is greatly prolonged by inhibiting its hydrolysing
enzyme, acetylcholinesterase.
 • The most commonly used anticholinesterase drug
is pyridostigmine, which is given orally in a dosage of
30-120 mg, usually 6-hourly.
 • Muscarinic side-effects, including diarrhoea and
colic, may be controlled by propantheline (15 mg as
required) or atropine.
11
Neurology
-
Dr.
Rami
Abo
Ali

12. MYASTHENIA GRAVIS
MANAGEMENT
 Disease modifying therapy
 1-Plasma exchange & Intravenous immunoglobulin
are normally reserved for myasthenic crisis or for pre-
operative preparation.
 2-Corticosteroid treatment can be extremely effective
in improving myasthenic weakness and establishing
remission.
 Improvement is commonly preceded by marked
exacerbation of myasthenic symptoms and treatment
should be initiated in hospital.
 It is usually necessary to continue treatment for
months or years, often resulting in adverse effects.
12
Neurology
-
Dr.
Rami
Abo
Ali

13. MYASTHENIA GRAVIS
MANAGEMENT:
 Other immunosuppressant treatment
 Include azathioprine, cyclosporine, tacrolimus and
mycophenolate mofetil, rituximab.
 Immunosuppressant treatment is of value if reducing
the dosage of steroids necessary and may allow
steroids to be withdrawn.
 surgical:
 Thymectomy in the early stages of the disease leads
to a much better overall prognosis, whether a
thymoma is present or not, in any antibody-positive
patient under 45 years with symptoms not confined to
extraocular muscles
13
Neurology
-
Dr.
Rami
Abo
Ali

14. MYASTHENIA GRAVIS
PROGNOSIS
 Remissions sometimes occur spontaneously.
 When myasthenia is confined to the eye muscles,
the prognosis is excellent and disability slight.
 Young female patients with generalized disease
have high remission rates after thymectomy.
14
Neurology
-
Dr.
Rami
Abo
Ali

15. LAMBERT-EATON MYASTHENIC SYNDROME
(LEMS)
 Neuromuscular transmition is impaired, often in
association with antibodies to presynaptic voltage-
gated calcium channels.
 It is characterized by muscle weakness which
improves after exercise.
 Patients may have autonomic dysfunction (and a dry
mouth).
 The cardinal clinical sign is absence of tendon
reflexes, which can return immediately after
sustained contraction of the relevant muscle.
 The condition is associated with underlying
malignancy, especially bronchogenic carcinoma, in a
high percentage of cases, and investigation must be
directed towards detecting such a cause. 15
Neurology
-
Dr.
Rami
Abo
Ali

16. LAMBERT-EATON MYASTHENIC SYNDROME
(LEMS)
 Diagnosis is made electrophysiologically on the
presence of post-tetanic potentiation of motor
response to nerve stimulation at a frequency of
20–50/sec.
 Treatment is with 3,4-diaminopyridine, or
pyridostigmine and immunosuppression.
16
Neurology
-
Dr.
Rami
Abo
Ali

17. 17
Neurology
-
Dr.
Rami
Abo
Ali

18. MYOPATHY
18
Neurology
-
Dr.
Rami
Abo
Ali

19. INTRODUCTION
 Muscle disease, either hereditary or acquired, is rare.
 Most typically, it presents with a proximal symmetrical
weakness.
 Diagnosis is dependent on recognition of clinical clues,
such as cardiorespiratory involvement, evolution,
family history, exposure to drugs, the presence of
contractures, myotonia and other systemic features,
and on investigation findings, most importantly EMG
and muscle biopsy.
 Hereditary syndromes include the muscular
dystrophies, muscle channelopathies, metabolic
myopathies (including mitochondrial diseases) and
congenital myopathies
19
Neurology
-
Dr.
Rami
Abo
Ali

20. EPIDEMIOLOGY
 Overall incidence of muscular dystrophy is about 63
per 1 million.
 Worldwide incidence of inflammatory myopathies is
about 5–10 per 100,000 people.
 More common in women
 Corticosteroid myopathy is the most common
endocrine myopathy and endocrine disorders are
more common in women
 Overall incidence of metabolic myopathies is
unknown.
20
Neurology
-
Dr.
Rami
Abo
Ali

21. MUSCLE UNIT ANATOMY
21
Neurology
-
Dr.
Rami
Abo
Ali

22. MOTOR UNIT
 A motor unit is made up of a motor neuron and all the muscle
cells it stimulates.
 vary in size
 Small motor units for precise, small movements
 large motor units for gross movements.
 The number of cells within a motor unit determines the degree
of movement when the motor unit is stimulated.
 Muscle tone is maintained by asynchronous stimulation of
random motor units.
22
Neurology
-
Dr.
Rami
Abo
Ali

23. CLASSIFICATION OF MUSCLE FIBER TYPES
23
Neurology
-
Dr.
Rami
Abo
Ali
There are two broad types of muscle fibre, which are functionally
different:
Type I fibers have low ATPase activity, are slow twitch, have high
oxidative and low glycolytic capacity, and are relatively resistant to
fatigue.
Type IIA fibers have high myosin ATPase activity, are fast twitch, have
high oxidative and glycolytic capacity, and are relatively resistant to
fatigue.
Type IIB fibers have high myosin ATPase activity, are fast twitch, have
low oxidative and high glycolytic capacity, and fatigue rapidly

24. 24
Neurology
-
Dr.
Rami
Abo
Ali

25. MUSCULAR DYSTROPHY
 Muscular dystrophy refers to a group of hereditary
progressive diseases each with unique phenotypic and
genetic features.
 Dystrophinopathies: Duchenne’s Muscular
Dystrophy and Becker’s Muscular Dystrophy
 Facioscapulohumeral muscular dystrophy
 Emery-Dreifus muscular dystrophy
 Limb-girdle muscular dystrophy
 Myotonic dystrophy
25
Neurology
-
Dr.
Rami
Abo
Ali

26. N
NOTE
 Dystrophin is a protein located between the
sarcolemma and the outermost layer of myofilaments
in the muscle fiber (myofiber).
 It is a cohesive protein, linking actin filaments to other
support proteins that reside on the inside surface of
each muscle fiber's plasma membrane (sarcolemma).
26
Neurology
-
Dr.
Rami
Abo
Ali

27. DUCHENNE’S MUSCULAR DYSTROPHY (DMD)
 Duchenne’s muscular dystrophy (DMD) also called pseudo
hypertrophic muscular dystrophy.
 It is an X linked recessive disorder.
 Dystrophin is deficient.
 The incidence of DMD is 1 in 3500 male births worldwide,
 DMD clinical feature:
 It is present at birth but becomes evident at 3-5 years.
 Gower’s maneuver
 Joint contractures, scoliosis, decreased pulmonary functions.
 By 16 to 18 years patients die of severe pulmonary infections
or aspiration pneumonia.
 Respitatory failure in 2nd or 3rd decade.
27
Neurology
-
Dr.
Rami
Abo
Ali

28. DUCHENNE’S MUSCULAR DYSTROPHY (DMD)
 Diagnosis
 The diagnosis of Duchenne muscular dystrophy is often made
clinically.
 The CK is grossly elevated (often 10 000 U/L).
 The EMG is myopathic and muscle biopsy shows fatty
infiltration and absence of staining for dystrophin.
 An accurate and rapid DNA diagnosis is now available,
allowing reliable identification of carrier status and prenatal
diagnosis if required.
 Management
 There is no cure for Duchenne muscular dystrophy, so the
management is supportive.
 Steroids may provide short-term improvement.
 Genetic counseling is important.
 Carrier females may have a raised CK and mildly myopathic
EMG, but without any clinical symptoms or signs
28
Neurology
-
Dr.
Rami
Abo
Ali

29. GOWER’S MANEUVER
29
Neurology
-
Dr.
Rami
Abo
Ali

30. BECKER’S MUSCULAR DYSTROPHY
 X linked recessive inheritance.
 Less severe form.
 Dystrophin muscle protein is deficient.
 The incidence of BMD is 5 in 100,000.
 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.
 Laboratory findings are similar to that of
Duchenne’s muscular dystrophy.
30
Neurology
-
Dr.
Rami
Abo
Ali

31. FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY (FSHD)
 Third most common after DMD and myotonic
 Onset of occurrence is childhood or young adulthood (age 3
to 44)
 Prevalence ranging from 1 in 20,000 to 1 in 455,000
 Autosomal dominant linked to chromosome 4q35
 Clinical feature
 Onset is incidious
 Difficulty in overhead activity
 Humeral muscle affected ( the biceps and triceps are
more severely affected while the deltoid and forearm
muscles are relatively spared) and this cause the
‘popeye’ appearance
 Weakness of the scapular muscles causes an abnormally
positioned scapula (winging) 31
Neurology
-
Dr.
Rami
Abo
Ali

32. EMERY–DREIFUSS MUSCULAR DYSTROPHY
 The X-linked form affects males, but females may
present with isolated cardiomyopathy and therefore
require cardiac evaluation.
 EDMD is characterized by a triad of clinical features:
 (1) early contractures in the elbows, Achilles
tendon, and posterior cervical spinal muscles
 (2) slowly progressive muscle weakness, which
begins in a humeroperoneal distribution;
 (3) cardiac abnormalities such as cardiomyopathy
and conduction defects.
32
Neurology
-
Dr.
Rami
Abo
Ali

33. LIMB–GIRDLE MUSCULAR DYSTROPHY
 Genetically heterogeneous group of disorders with an
autosomal dominant (LGMD 1) or autosomal
recessive (LGMD 2) mode of inheritance.
 The prevalence is approximately 8.1 in 1 million
inhabitants.
 Underlying pathophysiology is unknown.
 Clincal features;
 Lower limb and pelvic girdle weakness, later UL
weakness and scapular winging
 Facial and extraocular muscle spared
 Diaphragmatic weakness
 Cardiac abnormality 33
Neurology
-
Dr.
Rami
Abo
Ali

34. MYOTONIC DYSTROPHY
 Autosomal dominant mode of inheritance mapped to
chromosome 19q13,53 which codes for the myotonic
dystrophy protein kinase(DMPK).
 Incidence of myotonic dystrophy is approximately 13.5 in
100,000 live births, and the prevalence is 3 to 5 per
100,000.14.
 Clinical features:
 Slow progressive weakness of face, jaw and distal limb
 Frontal baldness, ptosis, and atrophy in the temporalis
and masseter muscles result in a characteristic
“hatchet-faced” appearance.
 Dysarthria and dysphagia
 Myotonia 34
Neurology
-
Dr.
Rami
Abo
Ali

35. 35
Neurology
-
Dr.
Rami
Abo
Ali

36. 36
Neurology
-
Dr.
Rami
Abo
Ali

37. 37
Neurology
-
Dr.
Rami
Abo
Ali