Dr Sadik Al-GHAZAWI

MRCP, FRCP UK

Myopathy

Muscular dystrophy:

-Are genitivally determined progressive necrotizing

myopathies

.

Classification:

X-linked recessive :

Duchenne

Becker Emery- Dreifuss

Autosomal dominant

:

Fascioscapulohumerar

.

Scapuloperoneal

Limb girdle

Myotonic

Oculopharyngear

Autosomal recessive:

Scapuloperoneal

Limb girdal

Duchenne dystrophy:

1:3500 male birth

1/3rd had negative family history

Delayed motor development is common; at 18 mths only 50% can walk.

Clumsiness is the first manifestation; this occur between 3-5 yrs.

Proximal muscle involvement is followed:

Waddling gait: glutei- quadriceps

Shoulder girdle & upper forearm.

Gouer's sign (not diagnostic)" climb up himself".

Psudohyperatrophy occur in 80% of cases.

Mean IQ is 15-20 points lower than the normal;

occasionally sever mental handicapped may occur

Progression:

Between 7-12 yrs –child no longer able to walk

,kyphoscoliosis with respiratory distress & cardiac

muscle involvement .

By age 20 yrs- chest infection, cardiac failure and

arrhythmias occur with severe muscle contracture ,

bedbound .

Survival is rare beyond mid 20s .

– Investigation:

Muscle enzyme- creatinine kinase especially in early stages,

the enzyme is raised at birth & is significantly elevated in the

female carrier useful for genetic counseling .

EMG: support the diagnosis , .

ECG : abnormal in 89% with conduction abnormality & rhythm

disorders.

Muscle biopsy : the failure to detect dystrophine establishes the

diagnosis beyond that .

Treatment:

There is no effective treatment.

Orthopedic procedure such as "tenotomy" may

prolong mobility

MYITONIA

failure of immediate muscle

relaxation after voluntary contraction

.

Patient grip an object then suddenly released it , the slow relaxation

and opening the hand grip will make the object appear "stuck" to the

fingers.

Physiology:

-Is due to instability of the Na & Cl channel of the muscle membrane

with repetitive discharges following a short period of contraction.

MYTONIA

Clinical feature:

❑Autosomal dominant .

❑Incidence 5/100000 with onset between 15-40 yrs.

❑Facial appearance is typical; frontal boldness, myopathic face ,ptosis

❑ , jaw hanging , wastening of muscles of mastication, hollowing of

temporal fossa & checks ,wastening of neck shoulder girdle muscle.

❑In the limbs : weakness & wastening are distal

❑ although the hands are spared until late .

❑Mental retardation is frequent.

❑As the disease progresses , myotonia become less

apparent and may disappear .

❑In affected mothers ,the disease may present in

the neonate with hypotonia , contracture & mental

retardation .

❑Ocular: ptosis –ophthalmoplegia, cataract, retinal pigmentary

abnormalities.

❑Cardiac : dilated cardiomyopathy, AV conduction defect.

❑Respiratory : diaphragmatic weakness, central sleep apnea.

❑Endocrine : infertility , insulin resistance DM.

❑N.B.: these features may predate or dominant over muscle

disease .

Investigation:

❑Creatine kinase(CK) is mildly elevated.

❑EMG shows classic features of myotonia, with

waxing & waning in the amplitude & frequency of

motor potentials, as well as myopathic changes .

Treatment :

❑Drugs blocking Na channels ( phenytoin ,

procainamid, quinine, & mexiletine), may reduce

myotonia .

❑Cardiac conduction defects may need a pace maker

.

❑Treatment of DM

❑Sedative drugs are to be avoid as patients show &

excessive sensitivity

❑Genetic counseling

Inflammatory myopathy:

Are disorders of muscles in which there is a clinical

& laboratory evidence of an inflammatory process.

Classification:

I –Polymyocytis:

a- Childhood form

b- Adult form

2- Dermatomyocytis

❑-

3-Inclusion body myocytis

4-Infammatory myopathy associated with malignant

disease.

5-Infammatory myopathy associated with collagen

vascular disorder.

6-Infective myopathy –e.g. viral ,cocksaki virus,

parasitic-e.g. toxoplasmosis, schistosomaiasis.

7-Drug induced – pencillamine, cholesterol lowering

agents, e.g. clowfibrate.

Polymyositis- Dermatomyocytis:

❑Annual incidence: 8/100000

❑Are sporadic though familial cases are described

❑An autoimmune bases for these disorder is

supported by :

❑Response to immunosuppressive therapy.

❑Associated with other non immunological

disorder

❑Elevated IgG in blood & presence of circulating

autoantibody

❑An increase incidence of histocompatibilty

antigens (HLA Ag)- B8,DR3.

❑ -Humoral & cell mediated immune mechanisms

seem responsible for these disorders but the

trigger factor remain unknown.

Clinical presentation:

❑-Onset is acute or subacute over a period of several

weeks & may follow systemic infection.

-Systemic symptoms prevail at the onset e.g.

lassitude, and are then followed by muscle weakness

.

- Extensive edema of skin & subcutaneous tissue is

common( especially in the orbital region).

Polymyositis:

Muscle may be painful & tender in 60% of cases

though onset is often painless.

Proximal muscles are first involved & initially

weakness may be asymmetrical.

Weakness of posterior neck muscles .

Occasionally weakness may

spread into distal muscle groups.

Pharyngeal & laryngeal

involvement result in dysphagia &

dysphonia.

Cardiac muscle may also be

involved.

Respiratory weakness causes respiratory failure (

this may be disproportionately sever).

The eye muscles are not involved unless there is co-

existant myasthenia gravis.

Reflexes are retained ( if absent ,considered under

lying carcinoma with added neuropathy .

Dermatomyocytis:

❑Often more severe & acute than polymyositis.

❑Characterized by skin rash

❑Violet discoloration of light exposed skin.

❑Heliotroeic discoloration of eyelid.

❑Raised scaly erythematous rash involving nose &

checks,

shoulders, extensor surface of limbs .

❑Telangiectasia and tighting of skin are common

& small

ulcerated vasculitic lesions develop over bony

proemences.

There are 2 types :

❑Adult form

❑Childhood form which is characterize by :

❑Multisystem involvement

❑Calcifications develops in skin & muscle with extrusion

through skin

❑Muscle contracture develop- tip- toe gait.

❑The muscle weakness is as in polymyocytis , but in

childhood dermatomyocytis may be very sever,

involving chewing , swallowing & breathing.

Differential diagnosis:

❑Inclusion body myocytis.

❑Limb girdle dystrophy.

❑Drug induced, toxic & metabolic myopathies.

Investigations

❑Muscle enzymes :elevated creatine kinase (CK),

which is realesed from necrotic muscle ,it is

an

indicator of disease activity and severity .

❑ EMG ,typical myopathic pattern.

❑Circulating Ab : rheumatoid factor, antinuclear

factor present in 40%.

❑ESR elevated in most patient.

❑Muscle biopsy shows necrosis of muscle fibers

with inflammatory

cells- lymphocytes, plasma cells, leucocytes.

Treatment:

❑Steroids –prednisolon 40-80 mg /day in divided

doses with gradual reduction to maintenance

(alternate days)once improved. If stopped too early,

relapse may occur. .

❑In refractory cases ,immunsuppressive drugs –

methotrexate

cyclosporine or high dose IV

immunoglobuline –may be used.

Outcome:

❑-Mortality is now low though only 10% recovered

completely.

❑- In the rest ,the disease become inactive after 2

years and patients are left with varying degrees of

disability.

❑- When associated with collagen disease, eventual

outcome will depend on the nature of that disease.

❑When associated with neoplasm, steroid may cause

temporary improvement

❑Removal of an associated tumor can result in

remission.

❑Death occurred as a result of respiratory failure ,

GI hemorrhage ,perforation & cardiac arrest.

❑Approximately 10% of adults with inflammatory

myopathy have underlying neoplasm.

❑In dermatomyocitis, of those over 40 yrs of age as

many as 60% harbor neoplasm.

❑Neoplasm may present before or after the development of

inflammatory myopathy.

❑Approximately 15% of adults with inflammatory myopathy

have

symptoms & signs of an associated collagen vascular disorder

❑In 5-10% of persons with these disorders , inflammatory

myopathy develops at some stage in their illness .

❑In mixed collagen vascular disease( overlap syndromes)

muscle

involvement is more common .

❑Inclusion body myositis:

❑Presents at age after 50 yrs.

❑Patchy & asymmetric in distribution.

❑Muscle biopsy shows basophilic inclusion granules.

❑Often clinically confused with polymyositis but

response to immunotherapy is poor.

❑Endocrine myopathies:

❑Unlike inflammatory myopathy ,the weakness in

these conditions is more chronic & is unassociated

pathologically with inflammation.

❑Correction of the underlying endocrine disturbance

results in recovery

1-Acromegaly:

❑-proximal weakness with fatigue

❑-entrapment neuropathy.

❑weakness occur in 20%

❑Shoulder girdle weakness is more marked than pelvic.

, fasciculation & atrophy may be present

❑Distinction must be made from MND .

❑Diagnosis is confirmed by thyroid function studies

Hypothyroidism:

❑Proximal weakness involves pelvic girdle more than

shoulder.

❑Painful cramps & muscle stiffness are common.

❑Nerve entrapment in limbs often occur.

❑There is always clinical evidence of

hypothyroidism.

❑Diagnosis is confirmed by thyroid function test and

response to hormone thyroid therapy is excellent.

❑Metabolic myopathies:

These disorders are characterized by defective

skeletal muscle

voltage- sensitive ion channels a (channelopathies).

I –Hypokalemic periodic paralysis:

❑- Autosomal dominant.

❑- Onset in the second decade.

❑Precipitated by exercise, carbohydrate load.

❑- Common in proximal lower limbs muscles & rapidly

becomes

generalize,

❑- Onset usually in morning on waking.

❑- Bulbar muscle- respiratory muscles unaffected

❑- K+ falls as low as 1.5meq /l.

❑Treatment:

Acute: -

oral KCl.

Prophylactic: –

acetazolamide ,low carbohydrate, high K+ diet.

With age, attacks become progressively less

frequent.

Non- familial hypokalemic periodic paralysis

may occur in patients suffering from hyperthyroidism

or on K+ - depleting diuretics.

Hyperkalemic periodic paralysis:

❑Autosomal Dominant or recessive.

❑Na + channel gene defect.

❑Onset in infancy – childhood.

❑Precipitated by rest after activity or by cold.

❑Commenses in lower limbs & evolves rapidly.

❑Attackes are of short duration ( less than 60 min).

❑Myotonia is evident in some patients.

❑K+ rises only slightly.

Treatment:

❑- Acute- IV Ca+ gluconate or NaCl .

❑ - Prophylactic – Na+ channel blocker, mexiletine.

Paramyotonia Congenita

❑Autosomal dominant

❑Na+ gene defect

❑Onset in infancy

❑Precipitated by rest after exercise, fasting & cooling.

❑Commence in proximal muscles.

❑Repetitive muscle contractions produce increasing

stiffness.

❑EMG findings are specific with marked

spontaneous activity in limb cooling.

❑Treatment: Na channel blocker mexiletine.

Myasthenia Gravis:

Characterized by :

❑Disorder of neuromuscular transmission due to an

autoimmune disruption of the NICOTINIC POST SYNAPTIC

RECEPTORS FOR ACETYLCHOLINE.

❑Weakness & fatigue of some or all muscle groups.

❑Weakness worsening on sustain or repeated exertion, or

towards the end of the day, relieved by rest.

❑Myasthenia Gravis is rare with a prevalence of 5/100000.

❑The increased incidence of autoimmune disorders in patients

& first

Etiology:

❑-Synaptic vesicles containing ACh within the presynaptic

nerve

ending, the release of Ach from vesicle to act on

cholinergic receptor sites is blocked by an immune process

attacks the neuromuscular junction.

❑Antibodies bind to receptors sites resulting in

there destruction

(complement mediated) .

These Ab are referred to as Ach receptors

Abs & are demonstrated by radioimmunoassay in

the serum of 90% of patients.

❑In human myasthenia gravis a reduction of ACH

receptors sites

has been demonstrated in the postsynaptic folds.

❑- Reduced receptors synthesis and increased

receptors destruction,

as well as the blocking of receptors response to Ach,

all seems

responsible for the disorder.

The role of the thymus:

Thyming abnormalities occur in 80% of patients.

The main function of the thymus to affect the

production of T-cell lymphocyte, which participates

in immune response.

Thymus dysfunction in a large number of disorders

which may be associated with myasthenia gravis

Changes are found in the thymus gland :

the gland is most active

during the induction of a normal immune responses

in the neonatal

period & attains its largest size at puberty after

which it involutes.

hyperplasia.

❑10% show thymoma.

❑Muscle biopsy :

❑lymphocyte infiltration with necrotic foci.

❑Muscle fiber atrophy

❑Diffuse muscle necrosis with inflammatory infiltration

when associated with thymoma.

❑Motor point biopsy may show abnormal motor endplates.

❑Light & electron microscopy show destruction of Ach

receptors with

simplification of the secondary folds of the postsynaptic

surface.

Clinical features:

❑-Up to 90% of patients present in adult life (<40

yrs of age), f: m is 2:1.

❑- The disorder may be selective, involving specific

group of muscle.

Several clinical subdivision are recognized:

a- Class 1-ocular muscle only- 20%

b- Class 2- mild generalized weakness.

c- class 3- moderate generalized & mild to moderate ocular-

bulbar weakness.

d- Class 4- sever generalized & ocular- bulbar weakness.

e- Class 5- myasthenic crisis

Note:

*approximztely 40% of class 1 will eventually become wide

spread, the rest remain purely ocular throughout the illness.

* Respiratory muscle involvement accompanies severe illness.

Cranial nerves signs & symptoms:

a- ocular involvement produces ptosis & muscle paresis .

b- weakness of jaw muscles allowes the mouth to hang open.

c- weakness of facial muscles results in expressionless

appearance.

d- on smilling, buccinator weakness produces a characteristic

smile (myasthenic snaril) .

e- bulbar involvement may result in : dysartheria, dysphonia,

dysphagia, nasal regurgitation of fluid & nasal quality of speech

.

f- the tongue occasionally shows the characteristic triple

grooved

appearance with two lateral & one central furro.

❑g- limb & trunk signs & symptoms:

❑Weakness of neck muscle may result in lolling of the head.

❑Proximal limb muscle are preferentially affected.

❑Fatigue may be demonstrated by movement against a

constant resistant.

❑Limb reflexes are often hyperactive and fatigue on repeated

testing.

❑Muscle wastenting occur in 15% of cases.

❑Stress, infection, pregnancy & drugs that altar

neuromuscular

transmission all exacerbate the weakness.

Natural history:

10% of patients entered a period of remission of long

duration

20% experienced short periods of remission

30% progressed to death

Differential diagnosis

-Easily fatigability –neurotic, depressed.

- Lambert-Eaton myasthenic syndrome.

Investigation:

1-Tensilon test (edrophonium)- short acting

anticholinesterase, 2-4min, given IV 2-10 mg slowly

with atropine available to counter muscarinic side

effect ( nausea, bradycardia).

-This is positive when noticeable improvement in

weakness occurs on objective testing.

-A controlled injection of saline is useful, especially

when assessing

-

limb weakness only.

The tensilon test may be negative in ocular

myasthenia & gives

a fales positive in Lambert Eaton syndrome

Electrophysiological study :

Reduction of amplitude of the compound muscle action

potential evoked by repetitive supramaximal nerve stimulation-

"

decriminating response". Various rates of stimulation, even as

low as 3/second may produce a decriminating response.

Single fiber EMG –measure of " Jitter"- the time interval variability of

action potentials from two single muscle fibers of the same motor

unit- is a more sensitive index of neuromuscular function & is

increased (95% of mild cases are abnormal).

Serological: Ach R Ab are detected in 90% 0f patients & are virtually

specific to this disease.

❑In ocular myasthenia ,

only 60% show Abs .

❑Magnitude of titers correlate with disease severity.

❑Other Abs e.g. microsomal, colloid, rheumatoid factor, gastric

parietal cell Ab – are ocusionally found.

❑These reflect the overlap between myasthenia gravis & other

autoimmune disorders.

❑Antistriated muscle Abs are found in 30% of all patients & in

90% of those with thymoma.

❑Additional test

❑–chest x-ray will show a large mediastinal mass but will not

exclude a small thymoma.

❑CT of chest should be performed in all newly diagnosed cases.

Treatment:

In severely ill patients, the first priority is to protect respiration by

intubation & ,if necessary, ventilation.

The anticholinesteras drugs:

inhibit cholinestras, the enzyme responsible for the break down of

acetylecholin, allowing enhanced receptors stimulation.

As a result, more ACH is available to affect neuromuscular

transmitters.

NB:

atropine may mask earl warning symptoms of this potential life-

threatening state.

Anticholinasterase drugs ( e.g. pyridostigmine- 4- hrs - oral,

neostegmin-2 hrs –IV, IM, oral, edrophonium IV 4 min.

Steroids:

because is this disorder is immune- mediated, steroids are a logical

choice in generalized & occasionally sever ocular disease,

prednisolon 60mg /day is initially used.

Deterioration may briefly occur before improvement.

Once a response occur, doses is reduced to alternate days.

Immnosuppresant : -

other than steroid (azathioprin, cyclophosphmid, cyclosporine )are

considered wit patient who don’t respond to steroid or who require

an unacceptably high steroid maintenance dose.

-

-Thymectomy: indications :

1- when thymoma is present

2- when myasthenia is generalized & benefits of

surgery outweigh risks.

Within 5 yrs of surgery , 80% of patients are in

remission.