myopathy undergraduate

DISORDERS OF SKELETAL MUSCLES

Osama RagabNeurology. MD

INTRODUCTION

Skeletal muscle is made up of large numbers of multinucleated muscle fibres, which have an outer membrane (sarcolemma) and cytoplasm (sarcoplasm) and in which lie the contractile components of the muscle (myofibrils).

The fibres are separated by connective tissue (endomysium) and arranged in bundles (fasciculi).

Each fasciculus has a connective tissue sheath (perimysium).

The muscle is made up of a number of fasciculi bound together and surrounded by a connective tissue sheath (epimysium).

INTRODUCTION

INTRODUCTION

DefinitionGroup of symptoms due to dysfunction of skeletal muscles .

Symptoms Motor manifestations: Weakness: bilateral . symmetrical affecting certain groups of muscle e.g. proximal. There may be a loss of tone (hypotonia)

INTRODUCTION

Changes in muscle bulkWasting of the affected musclesEnlargement of muscle may an early sign in certain dystrophies, (pseudohypertrophy).Changes in reflexesThese are usually preserved in muscle disorders, at least until wasting is severe, Changes in muscle contractilityMyotonia .

INTRODUCTION

PainPain is a rare complaint in primary muscle disease except in metabolic or inflammatory myopathy .It is important to ask about a change in the colour of urine, which can occur in some metabolic disorders.No sensory manifestationNo sphincter manifestation

CLASSIFICATION

A] Primary: Progressive muscle dystrophyB] Secondary: 1] Inflammatory: polymyositis 2] Metabolic: Periodic familial paralysis 3] Endocrinal: thyrotoxic .Chushing. 4] Drug induced: corticosteroid. Statin . 5] Miscellaneous: carcinomatous

CLASSIFICATION OF PROGRESSIVE MUSCLE DYSTROPHY

I – X–linked disorders :

a) Duchenne's muscular dystrophy (DMD).

b) Becker's muscular dystrophy (BMD) .

II – Autosomal recessive disorders :

Limb-Girdle muscular dystrophy .

III – Autosomal dominant disorders :

a) Fascio-scapulo-humeral muscular dystrophy .

b) Distal myopathy .

c) Ocular myopathy .

d) Oculo-pharyngeal myopathy .

MUSCULAR DYSTROPHIES

Dystrophinopathies include diseases of skeletal and cardiac muscle that are characterized by mutations in the dystrophin (DMD) gene on Xp21. The spectrum of clinical presentations include Duchenne’s muscular dystrophy (DMD, incidence 1:3500) and Becker’s muscular dystrophy (BMD, incidence 1:35,000).


Etiology and pathophysiologyDystrophin is a large filamentous protein that is integral part of the dystrophin–glycoprotein complex (DGC).The DGC is thought to provide structural integrity to individual myofibers during contraction.


presentation of Duchenne’s muscular dystrophy

Early (ages 2–6)Onset of walking delayed beyond 18 months. Abnormal gait with toe walking or waddling. Difficulty running. Frequent falls, difficulty rising from the floor (Gower’s sign). Prominent calf muscle bulge (‘pseudo-hypertrophy’). Hyperlordosis resulting in a protruding abdomen.In some patients there is global developmental delay, severe learning disabilities,

failure to thrive


Ages 7–10Progressive leg weakness leading to loss of walkingand wheelchair dependence by mean age of 9.5 years. Joint contractures, especially of the iliotibial bands, hip flexors, and heel cords.

Progressive scoliosis and thoracic deformities after loss of mobility


Teenage years Development of more apparent upper extremity weakness. Worsening respiratory reserve and sleep hypoventilation, and obstructive apnea.

Scoliosis progresses rapidly with the pubertal growth spurt, with adverse effects on respiration, feeding, sitting, and comfort.

In the past, most patients died in the late teens and early twenties.


General featuresCognitive impairment and mental retardation occur in a subset of DMD and BMD.

Cardiac involvement with conduction defects as well as cardiomyopathy is common in BMD and DMD.

INVESTIGATIONS AND DIAGNOSIS

A. EMG: myopathic changes early in the disease course. small amplitude, and polyphasic motor unit action potentials is the most typical appearance of a myopathy.

B. serum creatine phosphokinase (CPK; creatine kinase, CK): this is often significantly raise

C. Muscle biopsy with immunohistochemical studies and immunoblot analysis .

D. Genetic testing is the most efficient way to confirm the diagnosis in typical cases of DMD with a positive family history.


Becker’s muscular dystrophyBMD is characterized by a later onset of symptoms and a slower rate of progression then that of DMD.

The onset of disease is variable, but often not until teenage years, with the mean at 12 years and 90% before age 20.

The patients often show similar but milder features than those found in DMD. The mean age at loss of ambulation is in the fourth decade, but patients may live for many decades. For some, cardiomyopathy dominates the clinical presentation.


managementCorticosteroids or the prednisone derivative deflazocort are effective in delaying loss of mobility by 6 months to 2 years. This therapy may have an especially high long-term impact if it can decrease the development of scoliosis by allowing some of the pubertal growth spurt to occur before loss of mobility. Patients are typically started on 0.75 mg/kg/day to 1.5 mg/kg/day in the early ambulatory phase (4–6 years).


managementRehabilitation with knee–ankle–foot orthoses can prolong walking for some 18–24 months.Respiratory therapy includes inspiratory resistive exercises that may increase the endurance of respiratory muscles. Angiotensin-converting enzyme (ACE) inhibitors and/ or beta-adrenergic blockers may be beneficial in treating and potentially preventing/delaying cardiomyopathy.


managementGene replacement:• Use of viral vectors to replace a mutated dystrophin gene.•stem cells may help muscle repair. Blocking the effect of myostatin as a negative regulator of muscle mass could have a beneficial effect.

Myasthenia gravis

MYASTHENIA GRAVIS

Myasthenia gravis (MG) is an acquired autoimmune disorder characterized by fatigable and fluctuating muscle weakness preferentially affecting certain muscle groups.In most cases it results from serum antibodies targeting the acetylcholine receptors (AChR) on the postsynaptic membrane of the neuromuscular junction (NMJ)

MYASTHENIA GRAVIS

MG can occur at any age, but peaks at the 2nd decade and 6th–7th decades. Women are three times more likely to be affected than men before age 40.Incidence is nearly equal before puberty and after age 40. Men have a higher incidence after age 50.

MYASTHENIA GRAVIS

The hallmark of MG is fluctuating and fatigable muscle weakness that improves with rest.•Weakness to varying degrees affects the extraocular, facial, bulbar, limb, and axial muscles. Severe respiratory muscle involvement is seen in myastheniccrisis .

MYASTHENIA GRAVIS

MYASTHENIA GRAVIS

Work-upEdrophonium (Tensilon) test useful in MG patients with ocular symptoms. Repetitive nerve stimulation: successive stimulation shows decrement of muscle action potential in clinically weak muscle. Serum AChR antibodies found in up to 90% of patients.A subset of patients with seronegative MG may have MuSK antibodies.CT scan or MRI with contrast of anterior chest to look for thymomaThyroid-stimulating hormone, free T4 to rule out thyroid disease

MYASTHENIA GRAVIS

Work-up

MYASTHENIA GRAVIS

Symptomatic therapyCholinesterase inhibitors (pyridostigmine or neostigmine) slow the breakdown of acetylcholine, increasing its availability at the NMJ and overcoming antibody-induced block. Adverse effects are .(i) increased muscarinic activity, especially diarrhoea, which may be treated with antimuscarinic drugs such as atropine or propantheline. (ii) cholinergic crisis

MYASTHENIA GRAVIS

Immune therapy. Corticosteroids are used, which occasionally produce a paradoxical deterioration in the condition in the first 7–10 days of treatment – patients should be monitored closely. Azathioprine has a steroid-sparing effect but takes months to work.

MYASTHENIA GRAVIS

Immune therapyIntravenous immunoglobulin or plasmapheresis may prevent the need for ventilatory support, probably by washing out the abnormal antibodies. The role of thymectomy in the control of myasthenia remains contentious. Most authorities advocate thymectomy in young patients, increasing the chance of disease remission from 30 to 40% in 3 years.

MYASTHENIA GRAVIS

Absolutely contraindicated drugs :-Interferone α, botulinum toxin and D-penucillamine. Relatively contraindicated drugs :-Succinylcholine and other neuro-muscular blockers. Aminoglycoside antibiotics. Beta blockers and calcium channel blockers. Magnesium salts. Quinine, quinidine and procainamide.

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