Dr Sadik AlGHAZAWI MRCP FRCP UK Myopathy uscular

Dr Sadik Al-GHAZAWI MRCP, FRCP UK

Myopathy uscular dystrophy: -Are genitivally determined progressive necrotizing myopathies. Classification: X-linked recessive : Duchenne Becker Emery- Dreifuss M

Autosomal dominant : Fascioscapulohumerar. Scapuloperoneal Limb girdle Myotonic Oculopharyngear

Autosomal recessive: Scapuloperoneal Limb girdal

Duchenne dystrophy: 1: 3500 male birth 1/3 rd 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 , kypho scoliosis with respiratory distress & cardiac muscle involvement. By age 20 yrs- chest infection, cardiac failure and arrhyt hmias occur with severe muscle contracture , bedbound. Survival is rare beyond mid 20 s.

– 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 rela xation after voluntary contraction.

Patient grip an object then suddenly released it , the slow relaxation a nd 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: q. Autosomal dominant. q. Incidence 5/100000 with onset between 15 -40 yrs. q. Facial appearance is typical; frontal boldness, myopathic face , ptosis q , jaw hanging , wastening of muscles of mastication, hollowing of temporal fossa & checks , wastening of neck shoulder girdle muscle.

q. In the limbs : weakness & wastening are distal q although the hands are spared until late. q. Mental retardation is frequent. q. As the disease progresses , myotonia become less apparent and may disappear. q. In affected mothers , the disease may present in the neonate with hypotonia , contracture & mental retardation.

q. Ocular: ptosis –ophthalmoplegia, cataract, retinal pigmentary abnormalities. q. Cardiac : dilated cardiomyopathy, AV conduction defect. q. Respiratory : diaphragmatic weakness, central sleep apnea. q. Endocrine : infertility , insulin resistance DM. q. N. B. : these features may predate or dominant over muscle disease.

Investigation: q. Creatine kinase(CK) is mildly elevated. q. EMG shows classic features of myotonia, with ng & waning in the amplitude & frequency of otor potentials, as well as myopathic changes. waxi m

Treatment : q. Drugs blocking Na channels ( phenytoin , procainamid, quinine, & mexiletine), may reduce myotonia. q. Cardiac conduction defects may need a pace maker. q. Treatment of DM q. Sedative drugs are to be avoid as patients show & excessive sensitivity q. 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 q-

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: q. Annual incidence: 8/100000 q. Are sporadic though familial cases are described q. An autoimmune bases for these disorder is supported by : q. Response to immunosuppressive therapy.

q. Associated with other non immunological disorder q. Elevated Ig. G in blood & presence of circulating autoantibody q. An increase incidence of histocompatibilty antigens (HLA Ag)- B 8, DR 3. q -Humoral & cell mediated immune mechanisms seem responsible for these disorders but the trigger factor remain unknown.

Clinical presentation: q-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 coexistant myasthenia gravis. Reflexes are retained ( if absent , considered under lying carcinoma with added neuropathy.

Dermatomyocytis: q. Often more severe & acute than polymyositis. q. Characterized by skin rash q. Violet discoloration of light exposed skin.

q. Heliotroeic discoloration of eyelid. q. Raised scaly erythematous rash involving nose & checks, shoulders, extensor surface of limbs. q. Telangiectasia and tighting of skin are common & small ulcerated vasculitic lesions develop over bony proemences.

There are 2 types : q. Adult form q. Childhood form which is characterize by : q. Multisystem involvement q. Calcifications develops in skin & muscle with extrusion through skin

q. Muscle contracture develop- tip- toe gait. q. The muscle weakness is as in polymyocytis , but in child hood dermatomyocytis may be very sever, involv ing chewing , swallowing & breathing.

Differential diagnosis: q. Inclusion body myocytis. q. Limb girdle dystrophy. q. Drug induced, toxic & metabolic myopathies.

Investigations q. Muscle enzymes : elevated creatine kinase (CK), ch is realesed from necrotic muscle , it is indicator of disease activity and severity. q EMG , typical myopathic pattern. whi an

q. Circulating Ab : rheumatoid factor, antinuclear factor present in 40%. q. ESR elevated in most patient. q. Muscle biopsy shows necrosis of muscle fibers with inflammatory cells- lymphocytes, plasma cells, leucocytes.

Treatment: q. Steroids –prednisolon 40 -80 mg /day in divided s with gradual reduction to maintenance nate days)once improved. If stopped too early, lapse may occur. dose (alter re.

q. I n refractory cases , immunsuppressive drugs – methotrexate cyclosporine or high dose IV immunoglobuline –may be used.

Outcome: q-Mortality is now low though only 10% recovered completely. q- In the rest , the disease become inactive after 2 years and patients are left with varying degrees of disability. q- When associated with collagen disease, eventual outcome will depend on the nature of that disease. q. When associated with neoplasm, steroid may cause temporary improvement

q. Removal of an associated tumor can result in remission. q. Death occurred as a result of respiratory failure , GI hemorrhage , perforation & cardiac arrest. q. Approximately 10% of adults with inflammatory myopathy have underlying neoplasm. q. In dermatomyocitis, of those over 40 yrs of age as many as 60% harbor neoplasm.

q. Neoplasm may present before or after the development of inflammatory myopathy. q. Approximately 15% of adults with inflammatory myopathy have symptoms & signs of an associated collagen vascular disorder q. In 5 -10% of persons with these disorders , inflammatory athy develops at some stage in their illness. myop q. In mixed collagen vascular disease( overlap syndromes) muscle involvement is more common.

q. Inclusion body myositis: q. Presents at age after 50 yrs. q. Patchy & asymmetric in distribution. q. Muscle biopsy shows basophilic inclusion granules. q. Often clinically confused with polymyositis but response to immunotherapy is poor.

q. Endocrine myopathies: q. Unlike inflammatory myopathy , the weakness in hese conditions is more chronic & is unassociated pathologically with inflammation. t q. Correction of the underlying endocrine disturbance results in recovery

1 -Acromegaly: q-proximal weakness with fatigue q-entrapment neuropathy.

qweakness occur in 20% q. Shoulder girdle weakness is more marked than pelvic. , fasciculation & atrophy may be present q. Distinction must be made from MND. q. Diagnosis is confirmed by thyroid function studies

Hypothyroidism: q. Proximal weakness involves pelvic girdle more than shoulder. q. Painful cramps & muscle stiffness are common. q. Nerve entrapment in limbs often occur. q. There is always clinical evidence of hypothyroidism. q. Diagnosis is confirmed by thyroid function test and response to hormone thyroid therapy is excellent.

q. Metabolic myopathies: These disorders are characterized by defective skeletal muscle voltage- sensitive ion channels a (channelopathies). I –Hypokalemic periodic paralysis: q- Autosomal dominant. q- Onset in the second decade.

q. Precipitated by exercise, carbohydrate load. q- Common in proximal lower limbs muscles & rapidly becomes generalize, q- Onset usually in morning on waking. q- Bulbar muscle- respiratory muscles unaffected q- K+ falls as low as 1. 5 meq /l.

q. 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: q. Autosomal Dominant or recessive. q. Na + channel gene defect. q. Onset in infancy – childhood. q. Precipitated by rest after activity or by cold.

q. Commenses in lower limbs & evolves rapidly. q. Attackes are of short duration ( less than 60 min). q. Myotonia is evident in some patients. q. K+ rises only slightly. Treatment: q- Acute- IV Ca+ gluconate or Na. Cl. q - Prophylactic – Na+ channel blocker, mexiletine.

Paramyotonia Congenita q. Autosomal dominant q. Na+ gene defect q. Onset in infancy q. Precipitated by rest after exercise, fasting & cooling.

q. Commence in proximal muscles. q. Repetitive muscle contractions produce increasing stiffness. q. EMG findings are specific with marked spontaneous activity in limb cooling. q. Treatment: Na channel blocker mexiletine.

Myasthenia Gravis: Characterized by : q. Disorder of neuromuscular transmission due to an immune disruption of the NICOTINIC POST SYNAPTIC EPTORS FOR ACETYLCHOLINE. q. Weakness & fatigue of some or all muscle groups. auto REC

q. Weakness worsening on sustain or repeated exertion, or towards the end of the day, relieved by rest. q. Myasthenia Gravis is rare with a prevalence of 5/100000. q. The increased incidence of autoimmune disorders in patients & first

Etiology: q-Synaptic vesicles containing ACh within the presynaptic nerve ending, the release of Ach from vesicle to act on choli nergic receptor sites is blocked by an immune process a ttacks the neuromuscular junction.

q. 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.

q. In human myasthenia gravis a reduction of ACH receptors sites has been demonstrated in the postsynaptic folds. q- 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 p roduction 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.

q 10% show thymoma. q. Muscle biopsy : qlymphocyte infiltration with necrotic foci. q. Muscle fiber atrophy q. Diffuse muscle necrosis with inflammatory infiltration hen associated with thymoma. w

q. Motor point biopsy may show abnormal motor endplates. q. Light & electron microscopy show destruction of Ach receptors with simplification of the secondary folds of the postsynaptic surface.

Clinical features: q-Up to 90% of patients present in adult life (<40 yrs of age), f: m is 2: 1. q- 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 ocularbulbar 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 rooved appearance with two lateral & one central furro.

qg- limb & trunk signs & symptoms: q. Weakness of neck muscle may result in lolling of the head. q. Proximal limb muscle are preferentially affected. q. Fatigue may be demonstrated by movement against a constant resistant.

q. Limb reflexes are often hyperactive and fatigue on repeated testing. q. Muscle wastenting occur in 15% of cases. q. Stress, infection, pregnancy & drugs that altar neuromuscular ransmission all exacerbate the weakness. t

Natural history: 10% of patients entered a period of remission of long duration 2 0% 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 nesterase, 2 -4 min, given IV 2 -10 mg slowly anticholi with atropine available to counter muscarinic side effect ( nausea, bradycardia). -This is positive when noticeable improvement in akness occurs on objective testing. we

-A controlled injection of saline is useful, especial 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 a ction potentials from two single muscle fibers of the same motor unit- is a more sensitive index of neuromuscular function & is ncreased (95% of mild cases are abnormal). i Serological: Ach R Ab are detected in 90% 0 f patients & are virtually s pecific to this disease.

q. In ocular myasthenia , only 60% show Abs. q. Magnitude of titers correlate with disease severity. q. Other Abs e. g. microsomal, colloid, rheumatoid factor, gastric p arietal cell Ab – are ocusionally found. q. These reflect the overlap between myasthenia gravis & other autoim mune disorders.

q. Antistriated muscle Abs are found in 30% of all patients & in 90% of those with thymoma. q. Additional test q–chest x-ray will show a large mediastinal mass but will not exclude a small thymoma. q. CT of chest should be performed in all newly diagnosed cases.

Treatment: In severely ill patients, the first priority is to protect respiration by ubation & , if necessary, ventilation. int The anticholinesteras drugs: inhibit cholinestras, the enzyme responsible for the break down of ylecholin, allowing enhanced receptors stimulation. As a result, more ACH is available to affect neuromuscular mitters. acet trans

NB: atropine may mask earl warning symptoms of this potential lifethreatening state. Anticholinasterase drugs ( e. g. pyridostigmine- 4 - hrs - oral, stegmin-2 hrs –IV, IM, oral, edrophonium IV 4 min. neo

Steroids: because is this disorder is immune- mediated, steroids are a logical c hoice in generalized & occasionally sever ocular disease, pr ednisolon 60 mg /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 onsidered wit patient who don’t respond to steroid or who require an unacceptably high steroid maintenance dose. - c

-Thymectomy: indications : 1 - when thymoma is present 2 - when myasthenia is generalized & benefits of rgery outweigh risks. Within 5 yrs of surgery , 80% of patients are in remission. su